Disease overview

Alterations

122

Molecular (A)

100

Clinical (B–E)

Direct drugs

365

Via biomarker

211

Natural agents

Natural products

141

Merged ranked

580

With trial/literature evidence

Sources: Open Targets, HPO, ClinicalTrials.gov, DGIdb, ChEMBL, OSMF Chronic Disease Review, PubMed MeSH, PubMed Literature · Pipeline phase 7 · Updated 2026-07-05

Remission & chronicity

Spontaneous remission

Relapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication vs on) falls from 3.69x at 2 months to 1.34x at 5 years

Best-intervention remission

55-80% remain relapse-free at 1 year after well-managed discontinuation; psychotherapy (CBT) achieves comparable remission with better durability; psilocybin-assisted therapy showing 29-71% response at 3 months in treatment-resistant cases

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Moderate; narrows substantially over time for maintenance medication question

Primary barrier

practice

Barrier detail: Guidelines push long maintenance durations partly because short-term relapse risk is high, but long-term maintenance evidence is weaker than commonly assumed; psychotherapy significantly underutilized relative to medication

Last SoC change: 2023 — FDA approved esketamine (Spravato) nasal spray for TRD; 2023 FDA approved psilocybin-assisted therapy pathway (Australian TGA 2023, US FDA Breakthrough designation); first-line SSRIs unchanged since early 1990s

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0002009 · MESH: D003865 · UMLS_CUI: C0041696

Alterations

122 total · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
Depression	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
ADRA1A adrenoceptor alpha 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA1B adrenoceptor alpha 1B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA1D adrenoceptor alpha 1D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2A adrenoceptor alpha 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2B adrenoceptor alpha 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2C adrenoceptor alpha 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ALDH5A1 aldehyde dehydrogenase 5 family member A1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BLTP1 bridge-like lipid transfer protein family member 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Brief Psychiatric Rating Scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
CDH6 cadherin 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CELF4 CUGBP Elav-like family member 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CNTLN centlein	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CTTNBP2 cortactin binding protein 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Canadian Occupational Performance Measure- Performance subscale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Client Satisfaction Questionnaire	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Collaborative Decision Making Approach Measure	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
DRD1 dopamine receptor D1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD2 dopamine receptor D2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD3 dopamine receptor D3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD4 dopamine receptor D4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD5 dopamine receptor D5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Decision Skills Checklist	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Decision Skills Questionnaire	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
ESR1 estrogen receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FGF5 fibroblast growth factor 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FHIT fragile histidine triad diadenosine triphosphatase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA1 gamma-aminobutyric acid type A receptor subunit alpha1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA2 gamma-aminobutyric acid type A receptor subunit alpha2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA3 gamma-aminobutyric acid type A receptor subunit alpha3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA4 gamma-aminobutyric acid type A receptor subunit alpha4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA5 gamma-aminobutyric acid type A receptor subunit alpha5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA6 gamma-aminobutyric acid type A receptor subunit alpha6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB1 gamma-aminobutyric acid type A receptor subunit beta1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB2 gamma-aminobutyric acid type A receptor subunit beta2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB3 gamma-aminobutyric acid type A receptor subunit beta3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRD gamma-aminobutyric acid type A receptor subunit delta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRE gamma-aminobutyric acid type A receptor subunit epsilon	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG1 gamma-aminobutyric acid type A receptor subunit gamma1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG2 gamma-aminobutyric acid type A receptor subunit gamma2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG3 gamma-aminobutyric acid type A receptor subunit gamma3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRP gamma-aminobutyric acid type A receptor subunit pi	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRQ gamma-aminobutyric acid type A receptor subunit theta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN1 glutamate ionotropic receptor NMDA type subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2A glutamate ionotropic receptor NMDA type subunit 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2B glutamate ionotropic receptor NMDA type subunit 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2C glutamate ionotropic receptor NMDA type subunit 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN2D glutamate ionotropic receptor NMDA type subunit 2D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN3A glutamate ionotropic receptor NMDA type subunit 3A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN3B glutamate ionotropic receptor NMDA type subunit 3B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRM5 glutamate metabotropic receptor 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GSK3A glycogen synthase kinase 3 alpha	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GSK3B glycogen synthase kinase 3 beta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Goal Attainment Scaling	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
HRH1 histamine receptor H1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1A 5-hydroxytryptamine receptor 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1B 5-hydroxytryptamine receptor 1B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1D 5-hydroxytryptamine receptor 1D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1E 5-hydroxytryptamine receptor 1E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR1F 5-hydroxytryptamine receptor 1F	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2A 5-hydroxytryptamine receptor 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2B 5-hydroxytryptamine receptor 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2C 5-hydroxytryptamine receptor 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3A 5-hydroxytryptamine receptor 3A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3B 5-hydroxytryptamine receptor 3B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3C 5-hydroxytryptamine receptor 3C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3D 5-hydroxytryptamine receptor 3D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR3E 5-hydroxytryptamine receptor 3E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR4 5-hydroxytryptamine receptor 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR5A 5-hydroxytryptamine receptor 5A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR6 5-hydroxytryptamine receptor 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR7 5-hydroxytryptamine receptor 7	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Hamilton depression rating scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
IMPA1 inositol monophosphatase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Interest in adjunctive rehabilitative approaches	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
LRFN5 leucine rich repeat and fibronectin type III domain containing 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAOA monoamine oxidase A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAOB monoamine oxidase B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTNR1A melatonin receptor 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTNR1B melatonin receptor 1B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Maryland Assessment of Recovery in Serious Mental Illness	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Montgomery Asberg Depression Rating Scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
NCAM1 neural cell adhesion molecule 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NEGR1 neuronal growth regulator 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OLFM4 olfactomedin 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OPRD1 opioid receptor delta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OPRK1 opioid receptor kappa 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OPRM1 opioid receptor mu 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PAX5 paired box 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PCLO piccolo presynaptic cytomatrix protein	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE4B phosphodiesterase 4B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PTAR1 protein prenyltransferase alpha subunit repeat containing 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Personal and Social Performance scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Problem-Solving Decision-Making Scale for Mental Health	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Qualitative interviews	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Remission rate	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
SCN10A sodium voltage-gated channel alpha subunit 10	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN11A sodium voltage-gated channel alpha subunit 11	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN1A sodium voltage-gated channel alpha subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN2A sodium voltage-gated channel alpha subunit 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN3A sodium voltage-gated channel alpha subunit 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN4A sodium voltage-gated channel alpha subunit 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN5A sodium voltage-gated channel alpha subunit 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN7A sodium voltage-gated channel alpha subunit 7	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN8A sodium voltage-gated channel alpha subunit 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN9A sodium voltage-gated channel alpha subunit 9	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A2 solute carrier family 6 member 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A3 solute carrier family 6 member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A4 solute carrier family 6 member 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SORCS3 sortilin related VPS10 domain containing receptor 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SOX5 SRY-box transcription factor 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SOX6 SRY-box transcription factor 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
STK24 serine/threonine kinase 24	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Service Engagement Scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Shared Decision Making Questionnaire for Mental Health	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Shared Decision-Making Coding System	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Situational Motivation Scale for Schizophrenia Research	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Social Skills Performance Assessment	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
TCF4 transcription factor 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TLR4 toll like receptor 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TMEM106B transmembrane protein 106B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Treatment attendance	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, merged ranking, and clinical trial / literature evidence (top agents)

From opensourcemed.info/chronic-disease — Integrative interventions for improving outcomes in depression: a narrative review. Candidates for further study, not approved treatments.

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
AGOMELATINE	Small molecule	Approved	Strong	100	8 trials 13 Cochrane 23 Meta-analysis 49 Trial pubs 42 RCT View evidence Registry trials NCT01156415 — Open-label Long Term (52 Weeks) Safety and Tolerability of Agomelatine Sublingual Tablets in Major Depressive Disorder (MDD) (TERMINATED) PHASE3 NCT04589143 — A Double-blind, Placebo-controlled Study of Antidepressant Augmentation With Agomelatine (COMPLETED) PHASE4 NCT01488071 — A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication (COMPLETED) PHASE3 NCT01531309 — Pharmacokinetics of AGO178 in Participants With Liver Impairment (COMPLETED) PHASE1 NCT04181567 — Comparison of the Efficacy, Safety, and Relapse of ECT to ECT Plus Agomelatine for Depressed Patients (COMPLETED) PHASE4 NCT01110889 — Efficacy, Safety and Tolerability of Agomelatine Sublingual Tablets in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT00411099 — Efficacy, Safety and Tolerability of Agomelatine in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT01731899 — Agomelatine in Depressed Patients With Fibromyalgia (COMPLETED) Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Cochrane review A comprehensive review and meta-analysis of neurological side effects related to second-generation antidepressants in individuals with major depressive disorder (Behavioural brain research, 2023) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? (Current molecular pharmacology, 2022) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Efficacy and Acceptability of Licensed and Off-Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomised Trials (Acta psychiatrica Scandinavica, 2025) Meta-analysis Efficacy and Safety of Agomelatine in Depressed Patients with Diabetes: A Systematic Review and Meta-Analysis (International journal of molecular sciences, 2024) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Clinical trial publication Agomelatine as adjunctive therapy with SSRIs or SNRIs for major depressive disorder: a multicentre, double-blind, randomized, placebo-controlled trial (BMC medicine, 2025) Clinical trial publication Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study (European child & adolescent psychiatry, 2025) Clinical trial publication Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance (Clinical neuropharmacology, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
AMPHETAMINE	Small molecule	Approved	Strong	100	8 trials 2 Trial pubs 2 RCT View evidence Registry trials NCT02058693 — Adjunctive Mixed Salts Amphetamine for Depressed Adults With Incomplete Response to Current Antidepressant Therapy (COMPLETED) PHASE4 NCT06967857 — Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression (RECRUITING) PHASE2 NCT00985725 — SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder (COMPLETED) PHASE2 NCT00296686 — Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression (TERMINATED) PHASE4 NCT01435759 — SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE2 NCT01436162 — Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE3 NCT01148979 — Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder. (COMPLETED) PHASE4 NCT00905424 — Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant (COMPLETED) PHASE2 Published literature Systematic review Navigating the challenges of substance use and psychopathology in depression, bipolar disorder, and schizophrenia (Comprehensive psychiatry, 2025) Systematic review Amphetamine Use in the Elderly: A Systematic Review of the Literature (Current neuropharmacology, 2020) Clinical trial publication Longitudinal study of impact of medication for opioid use disorder on Hamilton Depression Rating Scale (Journal of affective disorders, 2022) Clinical trial publication Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (Journal of affective disorders, 2016) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ARIPIPRAZOLE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
BREXPIPRAZOLE	Small molecule	Approved	Strong	100	8 trials 6 Cochrane 15 Meta-analysis 27 Trial pubs 18 RCT View evidence Registry trials NCT01360632 — Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial) (COMPLETED) PHASE3 NCT01942785 — Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy (COMPLETED) PHASE3 NCT03487198 — The Safety and Efficacy of Brexpiprazole as Adjunctive Therapy in the Treatment of Major Depressive Disorder (TERMINATED) PHASE3 NCT01838681 — Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment (COMPLETED) PHASE3 NCT02212613 — Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability (WITHDRAWN) PHASE3 NCT04162522 — Canadian Biomarker Integration Network for Depression (CAN-BIND) - Validation Study (COMPLETED) PHASE3 NCT01360645 — Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial) (COMPLETED) PHASE3 NCT05017311 — Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D) (RECRUITING) PHASE4 Published literature Cochrane review Adjunctive Antipsychotics in Major Depressive Disorder: A Systematic Review and Network Meta-Analysis (JAMA psychiatry, 2026) Cochrane review Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis (Medicine, 2023) Cochrane review Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials (Journal of clinical pharmacology, 2022) Cochrane review Efficacy and safety of brexpiprazole in acute management of psychiatric disorders: a meta-analysis of randomized controlled trials (International clinical psychopharmacology, 2020) Cochrane review Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis (CNS drugs, 2019) Meta-analysis Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis (Neuropsychopharmacology reports, 2024) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Meta-analysis Efficacy and acceptability of second-generation antipsychotics with antidepressants in unipolar depression augmentation: a systematic review and network meta-analysis (Psychological medicine, 2022) Clinical trial publication Effects of Adjunctive Brexpiprazole in Major Depressive Disorder Analyzed by Baseline Anxiety Level: Post Hoc Analysis of a Phase 4 Study (Journal of clinical psychopharmacology, 2026) Clinical trial publication Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials (The international journal of neuropsychopharmacology, 2025) Clinical trial publication Patient-reported efficacy of adjunctive brexpiprazole in major depressive disorder in a phase 4, open-label, interventional study (Current medical research and opinion, 2025) Clinical trial publication Adjunctive brexpiprazole in patients with unresolved symptoms of depression on antidepressant treatment who are early in the disease course: post hoc analysis of randomized controlled trials (The international journal of neuropsychopharmacology, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
BUPROPION HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 4 Trial pubs 3 RCT View evidence Registry trials NCT00234195 — Wellbutrin XL, Major Depressive Disorder and Breast Cancer (COMPLETED) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT07523048 — Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder (RECRUITING) PHASE2 NCT01369290 — Electroencephalography (EEG) Signal Processing (UNKNOWN) NCT00590863 — Combining Medications to Enhance Depression Outcomes (COMPLETED) PHASE4 NCT00289523 — EEG Biomarkers for Predicting Response to Antidepressant Therapy (COMPLETED) NCT06417437 — Non-invasive BCI and Application Verification for Depressed People (RECRUITING) PHASE4 NCT00093288 — Major Depressive Disorder In The Elderly (COMPLETED) PHASE3 Published literature Clinical trial publication Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial (Journal of affective disorders, 2019) Clinical trial publication An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended-release in patients with major depressive disorder with atypical features (Pharmacopsychiatry, 2013) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) Clinical trial publication Cost-effectiveness of evidence-based pharmacotherapy or cognitive behavior therapy compared with community referral for major depression in predominantly low-income minority women (Archives of general psychiatry, 2005) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
CITALOPRAM	Small molecule	Approved	Strong	100	8 trials 27 Cochrane 46 Meta-analysis 248 Trial pubs 167 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Effects of the selective serotonin reuptake inhibitors citalopram and escitalopram on glucolipid metabolism: a systematic review (Frontiers in endocrinology, 2025) Cochrane review A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression (Harvard review of psychiatry, 2024) Cochrane review Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis (BMC psychiatry, 2023) Cochrane review Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis (Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 2022) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Meta-analysis Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Meta-analysis New generation antidepressants for depression in children and adolescents: a network meta-analysis (The Cochrane database of systematic reviews, 2021) Systematic review A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition (The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2025) Systematic review Amygdala biomarkers of treatment response in major depressive disorder: An fMRI systematic review of SSRI antidepressants (Psychiatry research. Neuroimaging, 2024) Clinical trial publication Efficacy of Acupuncture for Mild to Moderate Depression in Older People: Protocol for a Randomized Controlled Trial (JMIR research protocols, 2026) Clinical trial publication Further evidence of depressive symptomatology profile predicting treatment outcome (International journal of psychiatry in clinical practice, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
CITALOPRAM HYDROBROMIDE	Small molecule	Approved	Strong	100	8 trials 4 Trial pubs 4 RCT View evidence Registry trials NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT01557946 — Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression (COMPLETED) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00993876 — Cognitive Flexibility in Major Depression in the Course of Pharmacological and Psychotherapeutic Treatment (COMPLETED) NA NCT00655057 — Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression (COMPLETED) PHASE2, PHASE3 NCT04975724 — Safety of Liposom With Citalopram in Elderly Patients With Major Depressive Disorder (UNKNOWN) PHASE4 NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT02458690 — eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients (COMPLETED) PHASE2 Published literature Clinical trial publication Efficacy of Acupuncture for Mild to Moderate Depression in Older People: Protocol for a Randomized Controlled Trial (JMIR research protocols, 2026) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) Clinical trial publication A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer (Archives of otolaryngology--head & neck surgery, 2008) Clinical trial publication Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study (Archives of general psychiatry, 2007) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE	Small molecule	Approved	Strong	100	5 trials 6 Cochrane 8 Meta-analysis 20 Trial pubs 14 RCT View evidence Registry trials NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT00944996 — Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression (COMPLETED) NA NCT01944657 — Supplemental Transcranial Magnetic Stimulation (TMS) vs. Standard Medication Monotherapy for Treating Major Depression: An Exploratory Field Study (WITHDRAWN) NA NCT00704860 — Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (COMPLETED) PHASE4 NCT05952713 — Comparative Responses to 15 Different Antidepressants in Major Depressive Disorder (COMPLETED) Published literature Cochrane review Efficacy and dose-response relationships of antidepressants in the acute treatment of major depressive disorders: a systematic review and network meta-analysis (Chinese medical journal, 2025) Cochrane review Tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis (Systematic reviews, 2021) Cochrane review Beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses (Systematic reviews, 2021) Cochrane review Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic review (Progress in neuro-psychopharmacology & biological psychiatry, 2019) Cochrane review Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis (Lancet (London, England), 2018) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Meta-analysis Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis (Lancet (London, England), 2016) Clinical trial publication Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2023) Clinical trial publication Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration (CNS spectrums, 2019) Clinical trial publication Are antidepressants equally effective in the long-term treatment of major depressive disorder? (Human psychopharmacology, 2015) Clinical trial publication The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine (Journal of affective disorders, 2012) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DESVENLAFAXINE SUCCINATE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
DULOXETINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 2 Meta-analysis 2 Trial pubs 2 RCT View evidence Registry trials NCT00331799 — Pilot Study of Duloxetine in Psychological Resilience (COMPLETED) PHASE2 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT00062673 — Study of Duloxetine in Elderly Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT04347577 — Intestinal Flora and Major Depressive Disorders (UNKNOWN) NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT01369290 — Electroencephalography (EEG) Signal Processing (UNKNOWN) NCT00321490 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo and Active Control in Major Depressive Disorder (COMPLETED) PHASE3 NCT00849693 — A Study in the Treatment of Children and Adolescents With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Meta-analysis Comparative pain and mood effects in patients with comorbid fibromyalgia and major depressive disorder: secondary analyses of four pooled randomized controlled trials of duloxetine (Pain, 2011) Meta-analysis The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder (Current medical research and opinion, 2008) Clinical trial publication Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses (Archives of general psychiatry, 2011) Clinical trial publication Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial (The Journal of clinical psychiatry, 2002) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESCITALOPRAM	Small molecule	Approved	Strong	100	8 trials 31 Cochrane 58 Meta-analysis 367 Trial pubs 288 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 Published literature Cochrane review Preventing relapse in patients with major depressive disorder after an effective acute course of electroconvulsive therapy (Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2026) Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Effects of the selective serotonin reuptake inhibitors citalopram and escitalopram on glucolipid metabolism: a systematic review (Frontiers in endocrinology, 2025) Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies (Neuropsychopharmacology reports, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Meta-analysis Modeling the efficacy of a novel antidepressant zuranolone for major depressive disorder (Journal of affective disorders, 2026) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Meta-analysis Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis (Neuropsychopharmacology reports, 2024) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Systematic review Subgenual anterior cingulate cortex and antidepressant response to serotonergic and glutamatergic pharmacological treatments: a systematic review of neuroimaging studies (Progress in neuro-psychopharmacology & biological psychiatry, 2026) Systematic review Escitalopram and functional connectivity in major depressive disorder: A systematic review (Journal of psychopharmacology (Oxford, England), 2025) Clinical trial publication Obesity-related differences in amygdala and hippocampal volume and metabolism before and after a placebo-controlled antidepressant trial in major depressive disorder (Scientific reports, 2026) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESCITALOPRAM OXALATE	Small molecule	Approved	Strong	100	8 trials 6 Trial pubs 5 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial (JAMA network open, 2020) Clinical trial publication Neuronavigation-Guided rTMS for the Treatment of Depressive Patients With Suicidal Ideation: A Double-Blind, Randomized, Sham-Controlled Trial (Clinical pharmacology and therapeutics, 2020) Clinical trial publication Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial (Journal of affective disorders, 2019) Clinical trial publication Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial (JAMA otolaryngology-- head & neck surgery, 2013) Clinical trial publication Toward a neuroimaging treatment selection biomarker for major depressive disorder (JAMA psychiatry, 2013) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
IMIPRAMINE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMILNACIPRAN HYDROCHLORIDE	Small molecule	Approved	Strong	100	3 trials View evidence Registry trials NCT07253207 — Efficacy and Safety Study of Levomilnacipran Hydrochloride Extended-Release Capsules in Major Depressive Disorder (COMPLETED) PHASE3 NCT01488266 — Aripiprazole Augmentation Versus Switching to Different Class of Antidepressants in Major Depressive Disorder (UNKNOWN) NA NCT00225511 — Study Evaluating Effexor XR for Major Depression. (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MECAMYLAMINE	Small molecule	Approved	Strong	100	8 trials 3 Trial pubs 2 RCT View evidence Registry trials NCT01180400 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT01288079 — A Study to Assess the Safety and Effect of TC-5214 in Patients With Major Depressive Disorder. (TERMINATED) PHASE2 NCT01197508 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder. (COMPLETED) PHASE3 NCT01152554 — A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00319319 — Nicotinic Receptor Augmentation of SSRI Antidepressants (COMPLETED) PHASE2 NCT00692445 — TC-5214 as add-on the Treatment of Major Depressive Disorder (COMPLETED) PHASE2 NCT01157078 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT01153347 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD) (ACS chemical neuroscience, 2010) Clinical trial publication Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study (Journal of clinical psychopharmacology, 2008) Clinical trial publication Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamine (Depression and anxiety, 2002) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MIANSERIN	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Approved	Strong	100	8 trials 22 Cochrane 46 Meta-analysis 103 Trial pubs 75 RCT View evidence Registry trials NCT01962753 — Depression in the Elderly and Cerebral Amyloid Plaques: Characterization by [18F] AV-45 Affectives Symptoms and Amyloïd Plaques (ASAP) (COMPLETED) NA NCT00590863 — Combining Medications to Enhance Depression Outcomes (COMPLETED) PHASE4 NCT02441387 — Predictors of the Outcome of Late Life Depression (UNKNOWN) NCT06309472 — Trial of Mirtazapine for Depression in IBD (RECRUITING) PHASE2 NCT00926835 — Effect of Antidepressants on the Treatment for Korean Major Depressive Disorder Patients (TERMINATED) PHASE4 NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT02458690 — eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients (COMPLETED) PHASE2 NCT00021528 — Sequenced Treatment Alternatives to Relieve Depression (STARD) (COMPLETED) PHASE4 Published literature* Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Antidepressants for the treatment of depression in people with cancer (The Cochrane database of systematic reviews, 2023) Cochrane review The risks of adverse events with venlafaxine and mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder: a protocol for two separate systematic reviews with meta-analysis and Trial Sequential Analysis (Systematic reviews, 2023) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Cochrane review Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression (Journal of psychopharmacology (Oxford, England), 2023) Meta-analysis Clinical Potential of Mirtazapine in Anxiety and Trauma-Related Disorders: A Systematic Review and Meta-Analysis of Current Evidence (Human psychopharmacology, 2026) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis The risks of adverse events with mirtazapine for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis (BMC psychiatry, 2025) Systematic review The Efficacy of Pharmacological Treatment of Depression in Anorexia Nervosa and Underweight Patients: A Systematic Review (European eating disorders review : the journal of the Eating Disorders Association, 2026) Clinical trial publication Measurement-Based Care to Enhance Antidepressant Treatment Outcomes in Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2025) Clinical trial publication Consistent differential effects of bupropion and mirtazapine in major depression (Journal of affective disorders, 2025) Clinical trial publication Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study (Psychoneuroendocrinology, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
NICOTINE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
OLANZAPINE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
PAROXETINE	Small molecule	Approved	Strong	100	8 trials 33 Cochrane 59 Meta-analysis 201 Trial pubs 155 RCT View evidence Registry trials NCT00457106 — A Single-Blind Trial of Risperidone vs. Paroxetine for Treatment of Panic Attacks (COMPLETED) NA NCT00519012 — Benefits of Switching Antidepressants Following Early Nonresponse (UNKNOWN) PHASE4 NCT00385307 — Efficacy and Safety of SR58611A in Patients With Major Depressive Disorder (SIRIUS) (COMPLETED) PHASE3 NCT00048607 — Treatment of Patients With Major Depressive Disorder With MK0869 (0869-062)(COMPLETED) (COMPLETED) PHASE3 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00825058 — Efficacy and Safety of SR58611 Compared to Placebo and Paroxetine (COMPLETED) PHASE3 NCT00206765 — Risperidone vs. Paroxetine for Panic Attacks (TERMINATED) PHASE2 NCT01838681 — Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment (COMPLETED) PHASE3 Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Cochrane review The effect of paroxetine on heart rate variability in patients with major depressive disorder: A systematic review and meta-analysis (Journal of affective disorders, 2024) Cochrane review Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis (Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 2022) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Efficacy and Safety of Agomelatine in Depressed Patients with Diabetes: A Systematic Review and Meta-Analysis (International journal of molecular sciences, 2024) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Systematic review Subgenual anterior cingulate cortex and antidepressant response to serotonergic and glutamatergic pharmacological treatments: a systematic review of neuroimaging studies (Progress in neuro-psychopharmacology & biological psychiatry, 2026) Clinical trial publication Measurement-Based Care to Enhance Antidepressant Treatment Outcomes in Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2025) Clinical trial publication Interpersonal sensitivity and response to selective serotonin reuptake inhibitors in patients with acute major depressive disorder (Journal of affective disorders, 2024) Clinical trial publication Artificial intelligence approach for the analysis of placebo-controlled clinical trials in major depressive disorders accounting for individual propensity to respond to placebo (Translational psychiatry, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
PAROXETINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUETIAPINE FUMARATE	Small molecule	Approved	Strong	100	8 trials 20 Trial pubs 20 RCT View evidence Registry trials NCT00388973 — Efficacy and Safety Study of Seroquel SR in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT00321490 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo and Active Control in Major Depressive Disorder (COMPLETED) PHASE3 NCT02720198 — Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD (COMPLETED) PHASE3 NCT00892463 — Identifying Very Early Response to Seroquel Extended Release (XR) Augmentation for Major Depressive Disorder (COMPLETED) PHASE4 NCT01795326 — Physician Survey on Monitoring of Patients Treated With Quetiapine (COMPLETED) NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT00955474 — Seroquel Alone Versus Seroquel With an SSRI for Depression With Psychotic Symptoms (TERMINATED) PHASE4 NCT00320268 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo in Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication Analysis of potentially predictive factors of efficacy of adjunct extended-release quetiapine fumarate in patients with major depressive disorder (Journal of psychopharmacology (Oxford, England), 2015) Clinical trial publication The influence of Hatha yoga as an add-on treatment in major depression on hypothalamic-pituitary-adrenal-axis activity: a randomized trial (Journal of psychiatric research, 2014) Clinical trial publication Extended release quetiapine fumarate as adjunct to antidepressant therapy in patients with major depressive disorder: pooled analyses of data in patients with anxious depression versus low levels of anxiety at baseline (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2014) Clinical trial publication Quetiapine fumarate extended-release for the treatment of major depression with comorbid fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study (Arthritis & rheumatology (Hoboken, N.J.), 2014) Clinical trial publication Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression (Psychoneuroendocrinology, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
SERTRALINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 9 Trial pubs 9 RCT View evidence Registry trials NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00519012 — Benefits of Switching Antidepressants Following Early Nonresponse (UNKNOWN) PHASE4 NCT00177996 — Pharmacotherapy in Depression With Panic Spectrum (COMPLETED) PHASE4 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00174590 — Treatment of Major Depressive Disorder With Psychotic Features. (TERMINATED) PHASE3 NCT07015944 — Moving on After Breast Cancer Trial for Depressed Breast Cancer Survivors in Pakistan (RECRUITING) NA NCT00275197 — A Research Study to Compare the Treatments of a Combination of Elzasonan With Zoloft, to Zoloft Alone, or Placebo in People With Major Depressive Disorder (MDD) (COMPLETED) PHASE2 Published literature Clinical trial publication Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial (JAMA network open, 2020) Clinical trial publication Cortical Connectivity Moderators of Antidepressant vs Placebo Treatment Response in Major Depressive Disorder: Secondary Analysis of a Randomized Clinical Trial (JAMA psychiatry, 2020) Clinical trial publication Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial (JAMA psychiatry, 2018) Clinical trial publication The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial (JAMA psychiatry, 2013) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT04295941 — Long-term Study With Trazodone Once-a-Day (COMPLETED) NCT07210112 — Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ) (NOT_YET_RECRUITING) PHASE2 NCT01764867 — Algorithm Guided Treatment Strategies for Major Depressive Disorder (UNKNOWN) PHASE4 NCT00704860 — Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (COMPLETED) PHASE4 NCT00775203 — A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder. (COMPLETED) PHASE3 NCT07377682 — Real-world Clinical Response to Trazodone in Italy, Poland, and Romania (RECRUITING) NCT05889234 — Multimodal Magnetic Resonance Imaging-based Study of Electroconvulsive Efficacy Prediction in Adolescents With Depression: a Multicenter Prospective Cohort Study (UNKNOWN) NCT07328373 — Neurobiological and Genomic Predictors of Relapse in Depression (RECRUITING) Published literature Clinical trial publication The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder (Psychopharmacology bulletin, 2009) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
VENLAFAXINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
ACEBUTOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ALFUZOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ALFUZOSIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AMIODARONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMITRIPTYLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APOMORPHINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASENAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CARVEDILOL PHOSPHATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
CELIPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORMERODRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORPROMAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CLOZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CYCLOBENZAPRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CYPROHEPTADINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DAPIPRAZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DAPIPRAZOLE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DEBRISOQUIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DISULFIRAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIVALPROEX SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DOPAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DRONEDARONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
GUANABENZ Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
INDAPAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ISOPROTERENOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LEVETIRACETAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LEVONORDEFRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LISDEXAMFETAMINE DIMESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LURASIDONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METARAMINOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METARAMINOL BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHADONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOTRIMEPRAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHOXAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHOXAMINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHOXSALEN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METOPROLOL SUCCINATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MIDODRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MIDODRINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
MILNACIPRAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MODAFINIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NAFTOPIDIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NALIDIXIC ACID Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NAPHAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NEFAZODONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NIFEDIPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PAPAVERINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PERGOLIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENDIMETRAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYLEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLEPHRINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYLPROPANOLAMINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE POLISTIREX Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYTOIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PHENYTOIN SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PINDOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PRAZOSIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PROMAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPIOMAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPRANOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPYLHEXEDRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
QUETIAPINE FUMARATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SERTINDOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SILODOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SODIUM OXYBATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SUCCINIC ACID Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAMSULOSIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TAMSULOSIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TAZOBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TERAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TERAZOSIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
THIORIDAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIFLUOPERAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIMIPRAMINE MALEATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TROGLITAZONE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
VALPROATE SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
VALPROIC ACID Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ZIPRASIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMIBEGRON	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
APREPITANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CARIPRAZINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CELECOXIB	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXMECAMYLAMINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROMETHORPHAN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
EDIVOXETINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ICOSAPENT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
INSULIN HUMAN	Biologic	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
KETAMINE HYDROCHLORIDE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
LISDEXAMFETAMINE DIMESYLATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MEMANTINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLPHENIDATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MIFEPRISTONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MINOCYCLINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MODAFINIL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIPAMPERONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
PSILOCYBIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
RISPERIDONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SAREDUTANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ARMODAFINIL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ATICAPRANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
AZETUKALNER	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
BEFLOXATONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
BUPRENORPHINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
CHEMBL10316	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200574	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL4084119	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CLOZAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DOCONEXENT	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESMETHADONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ESZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
FEMOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
FLUOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
HALOPERIDOL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
INDIPLON	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
KETAMINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LIOTHYRONINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LITHIUM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LUMATEPERONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LURASIDONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MIDAZOLAM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NALOXONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NAVACAPRANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NOREPINEPHRINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
OLSALAZINE SODIUM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
OMEGA-3 FATTY ACIDS	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
PIMAVANSERIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
PRAMIPEXOLE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
QUETIAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
RAPASTINEL	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ROFLUMILAST	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ROSUVASTATIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SAMIDORPHAN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SELTOREXANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SEROTONIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SIMVASTATIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SOLRIAMFETOL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VALPROIC ACID	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VORTIOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
DARAPLADIB Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE	Small molecule	Phase II	Moderate	65	—	Open Targets, ChEMBL	ChEMBL Open Targets
ACETYLCYSTEINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ADEMETIONINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMITIFADINE HYDROCHLORIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CLAVULANIC ACID	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CYCLOSERINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROMETHORPHAN HYDROBROMIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
EZOGABINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
FARAMPATOR	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABOXADOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LANICEMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEUCINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LOSMAPIMOD	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
METYRAPONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALUZOTAN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NIACIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NITROUS OXIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
OMEGA-3-ACID ETHYL ESTERS	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ONABOTULINUMTOXINA	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ORVEPITANT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYTOCIN	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PENTOXIFYLLINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PINDOLOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUINIDINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
REBOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
RILUZOLE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SIRUKUMAB	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TASIMELTEON	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TEDATIOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TOCILIZUMAB	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
VERUCERFONT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
(+/-)NICOTINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ABX-002	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ACAMPROSATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ADENOSINE TRIPHOSPHATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALLOPURINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AMITIFADINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
APIMOSTINEL	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ATORVASTATIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AV-101	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AZD-7268	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AZD2066	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BARICITINIB	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BASIMGLURANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BREZIVAPTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BUSPIRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CASOPITANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CENTANAFADINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CERONAPRIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1200420	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1715	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107951	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2108243	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL25	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL451	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL521	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CLEMASTINE FUMARATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CP-601927	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CREATINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CRINECERFONT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CX-157	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DAPAGLIFLOZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DASATINIB	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DASOTRALINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DECOGLURANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DEXMECAMYLAMINE HYDROCHLORIDE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DIPHENHYDRAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DU 125530	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ELZASONAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EMESTEDASTAT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EMPAGLIFLOZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ESUPRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EVT-101	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FILOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FISH OIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FOSFOCREATINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
GSK163090	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
HYDROXYNORKETAMINE, (2R,6R)	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ICALCAPRANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
IGMESINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-18038683	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-26489112	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-39393406	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-40411813	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-42165279	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-54175446	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LEVODOPA	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LIAFENSINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LY-2940094	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LY2940094	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MAGNESIUM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MANIFAXINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MECAMYLAMINE HYDROCHLORIDE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MELATONIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MK-8777	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
N,N-DIMETHYLTRYPTAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NAPITANE MESYLATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NELIVAPTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NEMIFITIDE	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NS-2359	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NSI-189	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NV-5138	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONDANSETRON	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONFASPRODIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONO-2333MS	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ORG-34517	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PIOGLITAZONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
QUERCETIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
QUINIDINE SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
RADAFAXINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
RISLENEMDAZ	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ROPANICANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SARCOSINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SCOPOLAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SELENIUM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SEMAGLUTIDE	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM BENZOATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM LACTATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SOY ISOFLAVONES	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SULFORAPHANE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SURITOZOLE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SUVOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TEBIDEUTOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TRAMADOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TRAXOPRODIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ULOTARONT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VESTIPITANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VOLINANSERIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
YOHIMBINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZELATRIAZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZELQUISTINEL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZIPRASIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPRENOLOL Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMISULPRIDE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
METFORMIN	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PERAMPANEL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PEXACERFONT	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PROPOFOL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
BACLOFEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
BOTULINUM TOXIN TYPE A	Biologic	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
BRILAROXAZINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
CHEMBL1355736	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1741	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1751	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2103774	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2106049	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL545	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL63	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL714	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
DIAZOXIDE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
FOSIGOTIFATOR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
GSK1360707	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
HT-2157	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
HYDROCORTISONE ACETATE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
KETOPROFEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
MEMANTINE HYDROCHLORIDE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
MGS-0210	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
PF-04995274	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
PREGNENOLONE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
SALMONELLA TYPHI TY2 VI POLYSACCHARIDE ANTIGEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TADALAFIL	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TOFACITINIB	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TOLUDESVENLAFAXINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
VALGANCICLOVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
VILDAGLIPTIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
XENON	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
ZOLPIDEM	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
Curcumin OSMF review	Nutraceutical	Preclinical	Emerging	30	2 trials 2 Meta-analysis 9 Trial pubs 8 RCT View evidence Registry trials NCT01750359 — Efficacy and Safety Curcumin in Depression (COMPLETED) PHASE4 NCT01022632 — Effect of Curcumin as Nutraceutical in Patients of Depression (COMPLETED) NA Published literature Meta-analysis Curcumin for depression: a meta-analysis (Critical reviews in food science and nutrition, 2020) Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials (Phytotherapy research : PTR, 2016) Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication Tetrahydrocurcumin for Major Depressive Disorder with Therapeutic Potential and Mechanistic Insights from Clinical and Preclinical Studies (Molecular neurobiology, 2025) Clinical trial publication Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study (Neurotoxicity research, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) Clinical trial publication Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study (Journal of clinical psychopharmacology, 2015) Clinical trial publication Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2015) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Ibogaine OSMF review	Psychedelic	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Ketamine (Esketamine) OSMF review	Small molecule	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
MDMA-assisted therapy OSMF review	Psychedelic	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Magnesium OSMF review	Supplement	Preclinical	Emerging	30	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT07633080 — Magnesium Bisglycinate in Major Depressive Disorder (RECRUITING) NA NCT00797966 — Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder (COMPLETED) PHASE2 NCT07458022 — MAGNESIUM & SSRI VS SSRI ALONE AMONG PATIENTS OF MAJOR DEPRESSIVE DISORDER (ACTIVE_NOT_RECRUITING) PHASE2 NCT07198477 — Sleep Disturbances and Their Association With Serum Magnesium Level in Patients With Major Depressive Disorder (NOT_YET_RECRUITING) NCT03877393 — The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (UNKNOWN) NA NCT07521358 — Magnesium Supplementation With Fluoxetine for Cognitive Function in Depression (COMPLETED) NA NCT01941043 — A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment (COMPLETED) PHASE2 NCT04880460 — Effect of Magnesium Supplementation in Selective Serotonin Reuptake Inhibitors Treated Major Depressive Disorder Patients (COMPLETED) PHASE2 Published literature Clinical trial publication Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial (Scientific reports, 2024) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Omega-3 fatty acids (EPA/DHA) OSMF review	Supplement	Preclinical	Emerging	30	8 trials View evidence Registry trials NCT00816322 — The Effect of Fish Oil in Major Depressive Disorder (COMPLETED) NA NCT05774665 — Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression (ACTIVE_NOT_RECRUITING) PHASE2 NCT00618865 — Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy (COMPLETED) NA NCT00517036 — Omega-3 Fatty Acids for Treating Adults With Major Depression (COMPLETED) PHASE3 NCT01620502 — N-3 Polyunsaturated Fatty Acids in the Prevention and Treatment for IFN-induced Depression (COMPLETED) NA NCT03072823 — Omega-3 Polyunsaturated Fatty Acids on Major Depressive Disorder in Patients With Cardiovascular Diseases (COMPLETED) NA NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT00361374 — Safety and Effectiveness of Omega 3-Fatty Acids, EPA Versus DHA, for the Treatment of Major Depression (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Psilocybin OSMF review	Psychedelic	Preclinical	Emerging	30	8 trials 8 Cochrane 12 Meta-analysis 33 Trial pubs 25 RCT View evidence Registry trials NCT05434156 — ELE-101 Safety & Tolerability Study in Healthy Participants and Patients With Depression (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT06308653 — Psilocybin for Major Depressive Disorder (MDD) (ACTIVE_NOT_RECRUITING) PHASE3 NCT06624137 — Computer Game, Qualitative, and MEG/EEG Assessment of Serotonergic Psychedelics (RECRUITING) NCT05381974 — The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD (WITHDRAWN) PHASE2 NCT05399498 — Psilocybin in Co-occuring Major Depressive Disorder and Borderline Personality Disorder (COMPLETED) PHASE2 NCT05259943 — Microdosing Psychedelics to Improve Mood (COMPLETED) PHASE2 NCT06141876 — Evaluation of Psilocybin-Assisted Psychotherapy in Treating Severe Depression in Patients With PTSD (UNKNOWN) PHASE2 NCT03181529 — Effects of Psilocybin in Major Depressive Disorder (COMPLETED) PHASE2 Published literature Cochrane review Therapeutic effects of psilocybin in major depressive disorder: a systematic review and meta-analysis exploring dose effects (European archives of psychiatry and clinical neuroscience, 2026) Cochrane review Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials (Psychiatry research, 2025) Cochrane review Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis (Acta psychiatrica Scandinavica, 2025) Cochrane review Psilocybin for major depressive disorder: An updated systematic review and meta-analysis of randomized clinical trials (Journal of psychopharmacology (Oxford, England), 2026) Cochrane review [Treatment-resistant depression. From classification to new therapies.] (Rivista di psichiatria, 2022) Meta-analysis Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis (Journal of affective disorders, 2026) Meta-analysis Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis (Neuroscience and biobehavioral reviews, 2026) Meta-analysis Breaking the chains of depression: A systematic review and meta-analysis of psilocybin therapy (Journal of affective disorders, 2026) Meta-analysis Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis (JAMA network open, 2025) Systematic review Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal (Journal of affective disorders, 2026) Clinical trial publication Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial (JAMA network open, 2026) Clinical trial publication Evaluation of a facilitator training program in a randomized controlled trial of psilocybin treatment for depression (BMC medical education, 2026) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
SAMe (S-adenosylmethionine) OSMF review	Supplement	Preclinical	Emerging	30	4 trials View evidence Registry trials NCT04832178 — Sumor as Adjuvant Therapy in Treatment-resistant Major Depression (UNKNOWN) PHASE4 NCT01912196 — Add-On Study of MSI-195 (S-Adenosyl-L-Methionine, SAMe) for Patients With Major Depressive Disorder (MDD) (COMPLETED) PHASE2 NCT00101452 — Safety and Effectiveness of S-adenosyl-l-methionine (SAMe) for the Treatment of Major Depression (COMPLETED) NA NCT04623034 — Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Saffron (Crocus sativus) OSMF review	Herbal	Preclinical	Emerging	30	1 Meta-analysis 4 Trial pubs 4 RCT View evidence Published literature Meta-analysis Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials (Journal of integrative medicine, 2013) Systematic review A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes (Journal of integrative medicine, 2015) Clinical trial publication Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial (Pharmacopsychiatry, 2017) Clinical trial publication Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial (Journal of affective disorders, 2015) Clinical trial publication Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study (Human psychopharmacology, 2013) Clinical trial publication Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial (Psychopharmacology, 2012) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
St. John's Wort (Hypericum perforatum) OSMF review	Herbal	Preclinical	Emerging	30	4 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT00005013 — Treatment of Major Depression With St. John's Wort (Hypericum) (COMPLETED) NA NCT04315597 — Study to Learn About Relapse Prevention of Hypericumextract (a Drug Based on the Plant St. John Wort) in Outpatients Suffering From Moderate Depressive Episodes (COMPLETED) PHASE3 NCT00451516 — St. John's Wort And Kava In The Treatment Of Major Depressive Disorder With Comorbid Anxiety (COMPLETED) PHASE2 NCT05477472 — Low Dose St John's Wort for Depression (COMPLETED) Published literature Clinical trial publication St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT (Pharmacopsychiatry, 2012) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Vitamin D OSMF review	Supplement	Preclinical	Emerging	30	7 trials 2 Cochrane 4 Meta-analysis 11 Trial pubs 10 RCT View evidence Registry trials NCT04898725 — Effects of Vitamin D Supplementation on Depression and Inflammatory Markers (COMPLETED) NA NCT01390662 — Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression (UNKNOWN) PHASE4 NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT01932931 — Vitamin D, SSRIs and the Musculoskeletal System (COMPLETED) NA NCT03754712 — Effect of Vitamin D Administration Along With SSRIs in Patients With Major Depressive Disorder (UNKNOWN) NA NCT07579078 — Effect of Vitamin D Supplementation on Brain Waves in Female Major Depressive Disorder Patients With Hypovitaminosis D (ENROLLING_BY_INVITATION) NA NCT00005119 — Altered Calcium and Vitamin D in PMDD or Severe PMS (COMPLETED) NA Published literature Cochrane review Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials (Nutrition (Burbank, Los Angeles County, Calif.), 2023) Cochrane review Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials (Journal of postgraduate medicine, 2019) Meta-analysis Genome-wide interaction study with major depression identifies novel variants associated with cognitive function (Molecular psychiatry, 2022) Meta-analysis The effect of vitamin D supplement on negative emotions: A systematic review and meta-analysis (Depression and anxiety, 2020) Systematic review Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials (Nutritional neuroscience, 2023) Systematic review Nutrient and genetic biomarkers of nutraceutical treatment response in mood and psychotic disorders: a systematic review (Nutritional neuroscience, 2021) Clinical trial publication Do probiotics modulate dietary intake? Pilot data from a randomized controlled sub-study of the ProBioHRV clinical trial in patients with depression and healthy controls (PloS one, 2026) Clinical trial publication Effect of a six-month vitamin D supplementation on depressive symptoms in patients with major depressive episode (DepFuD): a double-blinded randomised controlled trial (Journal of affective disorders, 2026) Clinical trial publication Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trial (Clinical nutrition (Edinburgh, Scotland), 2026) Clinical trial publication The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial (Psychological medicine, 2024) Clinical trial publication Effects of Vitamin D(3) and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL) (The Journal of clinical psychiatry, 2023) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
(+)-TRANYLCYPROMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ALAPROCLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMINEPTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMITRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMITRIPTYLINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMOXAPINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BETAINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BIFEMELANE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BREXANOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUPROPION	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUPROPION HYDROBROMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CALCIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CENTANAFADINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL142438	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CHOLINE ALFOSCERATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CILOSTAZOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CITICOLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLOVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CYSTEAMINE BITARTRATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESIPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESIPRAMINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESVENLAFAXINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESVENLAFAXINE FUMARATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DEXAMETHASONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIBENZEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIMETACRINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIVALPROEX SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOTHIEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOXEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOXEPIN HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DULOXETINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESKETAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESKETAMINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETOPERIDONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FISH OIL TRIGLYCERIDES	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUDROCORTISONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUOXETINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GANAXOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEMIBOTULINUMTOXIN A	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEPIRONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEPIRONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GHRELIN	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GOLIMUMAB	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GR-127935	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GW 3965	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IMIPRAMINOXIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPRINDOLE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPROCLOZIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPRONIAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ISOCARBOXAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LAMOTRIGINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LEVOMEFOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LEVOMILNACIPRAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LIOTHYRONINE SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LITHIUM CARBONATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LOFEPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LORAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAPROTILINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAPROTILINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MEDIFOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MELITRACEN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MILNACIPRAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MINAPRINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MOCLOBEMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NALOXONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NEFAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NEFAZODONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NIALAMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NOMIFENSINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NORTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NORTRIPTYLINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OPIPRAMOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OXAFLOZANE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OXITRIPTAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PAROXETINE MESYLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PHENELZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PIVAGABINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PIZOTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PROTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
QUINUPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
RAMELTEON	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ROPINIROLE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SELEGILINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SERTRALINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SILDENAFIL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SODIUM CITRATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ST. JOHN'S WORT	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SULPIRIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TESTOSTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TIANEPTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TOLOXATONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TOLUDESVENLAFAXINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRANYLCYPROMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRANYLCYPROMINE SULFATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRIMIPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRYPTOPHAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TYROSINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ULOTARONT HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE BESYLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILAZODONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILOXAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VORTIOXETINE HYDROBROMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZIMELDINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZINC SULFATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZURANOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
AGOMELATINE	Small molecule	Approved	Strong	100	8 trials 13 Cochrane 23 Meta-analysis 49 Trial pubs 42 RCT View evidence Registry trials NCT01156415 — Open-label Long Term (52 Weeks) Safety and Tolerability of Agomelatine Sublingual Tablets in Major Depressive Disorder (MDD) (TERMINATED) PHASE3 NCT04589143 — A Double-blind, Placebo-controlled Study of Antidepressant Augmentation With Agomelatine (COMPLETED) PHASE4 NCT01488071 — A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication (COMPLETED) PHASE3 NCT01531309 — Pharmacokinetics of AGO178 in Participants With Liver Impairment (COMPLETED) PHASE1 NCT04181567 — Comparison of the Efficacy, Safety, and Relapse of ECT to ECT Plus Agomelatine for Depressed Patients (COMPLETED) PHASE4 NCT01110889 — Efficacy, Safety and Tolerability of Agomelatine Sublingual Tablets in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT00411099 — Efficacy, Safety and Tolerability of Agomelatine in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT01731899 — Agomelatine in Depressed Patients With Fibromyalgia (COMPLETED) Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Cochrane review A comprehensive review and meta-analysis of neurological side effects related to second-generation antidepressants in individuals with major depressive disorder (Behavioural brain research, 2023) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? (Current molecular pharmacology, 2022) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Efficacy and Acceptability of Licensed and Off-Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomised Trials (Acta psychiatrica Scandinavica, 2025) Meta-analysis Efficacy and Safety of Agomelatine in Depressed Patients with Diabetes: A Systematic Review and Meta-Analysis (International journal of molecular sciences, 2024) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Clinical trial publication Agomelatine as adjunctive therapy with SSRIs or SNRIs for major depressive disorder: a multicentre, double-blind, randomized, placebo-controlled trial (BMC medicine, 2025) Clinical trial publication Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study (European child & adolescent psychiatry, 2025) Clinical trial publication Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance (Clinical neuropharmacology, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ARIPIPRAZOLE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
BREXPIPRAZOLE	Small molecule	Approved	Strong	100	8 trials 6 Cochrane 15 Meta-analysis 27 Trial pubs 18 RCT View evidence Registry trials NCT01360632 — Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial) (COMPLETED) PHASE3 NCT01942785 — Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy (COMPLETED) PHASE3 NCT03487198 — The Safety and Efficacy of Brexpiprazole as Adjunctive Therapy in the Treatment of Major Depressive Disorder (TERMINATED) PHASE3 NCT01838681 — Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment (COMPLETED) PHASE3 NCT02212613 — Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability (WITHDRAWN) PHASE3 NCT04162522 — Canadian Biomarker Integration Network for Depression (CAN-BIND) - Validation Study (COMPLETED) PHASE3 NCT01360645 — Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial) (COMPLETED) PHASE3 NCT05017311 — Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D) (RECRUITING) PHASE4 Published literature Cochrane review Adjunctive Antipsychotics in Major Depressive Disorder: A Systematic Review and Network Meta-Analysis (JAMA psychiatry, 2026) Cochrane review Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis (Medicine, 2023) Cochrane review Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials (Journal of clinical pharmacology, 2022) Cochrane review Efficacy and safety of brexpiprazole in acute management of psychiatric disorders: a meta-analysis of randomized controlled trials (International clinical psychopharmacology, 2020) Cochrane review Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis (CNS drugs, 2019) Meta-analysis Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis (Neuropsychopharmacology reports, 2024) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Meta-analysis Efficacy and acceptability of second-generation antipsychotics with antidepressants in unipolar depression augmentation: a systematic review and network meta-analysis (Psychological medicine, 2022) Clinical trial publication Effects of Adjunctive Brexpiprazole in Major Depressive Disorder Analyzed by Baseline Anxiety Level: Post Hoc Analysis of a Phase 4 Study (Journal of clinical psychopharmacology, 2026) Clinical trial publication Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials (The international journal of neuropsychopharmacology, 2025) Clinical trial publication Patient-reported efficacy of adjunctive brexpiprazole in major depressive disorder in a phase 4, open-label, interventional study (Current medical research and opinion, 2025) Clinical trial publication Adjunctive brexpiprazole in patients with unresolved symptoms of depression on antidepressant treatment who are early in the disease course: post hoc analysis of randomized controlled trials (The international journal of neuropsychopharmacology, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
BUPROPION HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 4 Trial pubs 3 RCT View evidence Registry trials NCT00234195 — Wellbutrin XL, Major Depressive Disorder and Breast Cancer (COMPLETED) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT07523048 — Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder (RECRUITING) PHASE2 NCT01369290 — Electroencephalography (EEG) Signal Processing (UNKNOWN) NCT00590863 — Combining Medications to Enhance Depression Outcomes (COMPLETED) PHASE4 NCT00289523 — EEG Biomarkers for Predicting Response to Antidepressant Therapy (COMPLETED) NCT06417437 — Non-invasive BCI and Application Verification for Depressed People (RECRUITING) PHASE4 NCT00093288 — Major Depressive Disorder In The Elderly (COMPLETED) PHASE3 Published literature Clinical trial publication Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial (Journal of affective disorders, 2019) Clinical trial publication An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended-release in patients with major depressive disorder with atypical features (Pharmacopsychiatry, 2013) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) Clinical trial publication Cost-effectiveness of evidence-based pharmacotherapy or cognitive behavior therapy compared with community referral for major depression in predominantly low-income minority women (Archives of general psychiatry, 2005) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
CITALOPRAM	Small molecule	Approved	Strong	100	8 trials 27 Cochrane 46 Meta-analysis 248 Trial pubs 167 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Effects of the selective serotonin reuptake inhibitors citalopram and escitalopram on glucolipid metabolism: a systematic review (Frontiers in endocrinology, 2025) Cochrane review A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression (Harvard review of psychiatry, 2024) Cochrane review Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis (BMC psychiatry, 2023) Cochrane review Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis (Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 2022) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Meta-analysis Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Meta-analysis New generation antidepressants for depression in children and adolescents: a network meta-analysis (The Cochrane database of systematic reviews, 2021) Systematic review A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition (The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2025) Systematic review Amygdala biomarkers of treatment response in major depressive disorder: An fMRI systematic review of SSRI antidepressants (Psychiatry research. Neuroimaging, 2024) Clinical trial publication Efficacy of Acupuncture for Mild to Moderate Depression in Older People: Protocol for a Randomized Controlled Trial (JMIR research protocols, 2026) Clinical trial publication Further evidence of depressive symptomatology profile predicting treatment outcome (International journal of psychiatry in clinical practice, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
CITALOPRAM HYDROBROMIDE	Small molecule	Approved	Strong	100	8 trials 4 Trial pubs 4 RCT View evidence Registry trials NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT01557946 — Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression (COMPLETED) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00993876 — Cognitive Flexibility in Major Depression in the Course of Pharmacological and Psychotherapeutic Treatment (COMPLETED) NA NCT00655057 — Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression (COMPLETED) PHASE2, PHASE3 NCT04975724 — Safety of Liposom With Citalopram in Elderly Patients With Major Depressive Disorder (UNKNOWN) PHASE4 NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT02458690 — eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients (COMPLETED) PHASE2 Published literature Clinical trial publication Efficacy of Acupuncture for Mild to Moderate Depression in Older People: Protocol for a Randomized Controlled Trial (JMIR research protocols, 2026) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) Clinical trial publication A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer (Archives of otolaryngology--head & neck surgery, 2008) Clinical trial publication Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study (Archives of general psychiatry, 2007) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DESVENLAFAXINE SUCCINATE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
DULOXETINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 2 Meta-analysis 2 Trial pubs 2 RCT View evidence Registry trials NCT00331799 — Pilot Study of Duloxetine in Psychological Resilience (COMPLETED) PHASE2 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT00062673 — Study of Duloxetine in Elderly Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT04347577 — Intestinal Flora and Major Depressive Disorders (UNKNOWN) NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT01369290 — Electroencephalography (EEG) Signal Processing (UNKNOWN) NCT00321490 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo and Active Control in Major Depressive Disorder (COMPLETED) PHASE3 NCT00849693 — A Study in the Treatment of Children and Adolescents With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Meta-analysis Comparative pain and mood effects in patients with comorbid fibromyalgia and major depressive disorder: secondary analyses of four pooled randomized controlled trials of duloxetine (Pain, 2011) Meta-analysis The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder (Current medical research and opinion, 2008) Clinical trial publication Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses (Archives of general psychiatry, 2011) Clinical trial publication Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial (The Journal of clinical psychiatry, 2002) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESCITALOPRAM	Small molecule	Approved	Strong	100	8 trials 31 Cochrane 58 Meta-analysis 367 Trial pubs 288 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT01312922 — Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 Published literature Cochrane review Preventing relapse in patients with major depressive disorder after an effective acute course of electroconvulsive therapy (Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2026) Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Effects of the selective serotonin reuptake inhibitors citalopram and escitalopram on glucolipid metabolism: a systematic review (Frontiers in endocrinology, 2025) Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies (Neuropsychopharmacology reports, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Meta-analysis Modeling the efficacy of a novel antidepressant zuranolone for major depressive disorder (Journal of affective disorders, 2026) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Meta-analysis Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis (Neuropsychopharmacology reports, 2024) Meta-analysis Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis (Nutrition reviews, 2025) Systematic review Subgenual anterior cingulate cortex and antidepressant response to serotonergic and glutamatergic pharmacological treatments: a systematic review of neuroimaging studies (Progress in neuro-psychopharmacology & biological psychiatry, 2026) Systematic review Escitalopram and functional connectivity in major depressive disorder: A systematic review (Journal of psychopharmacology (Oxford, England), 2025) Clinical trial publication Obesity-related differences in amygdala and hippocampal volume and metabolism before and after a placebo-controlled antidepressant trial in major depressive disorder (Scientific reports, 2026) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESCITALOPRAM OXALATE	Small molecule	Approved	Strong	100	8 trials 6 Trial pubs 5 RCT View evidence Registry trials NCT01034995 — A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder (COMPLETED) PHASE2 NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00166114 — Depression, Epinephrine, and Platelet Function (COMPLETED) PHASE4 NCT00464711 — Brain GABA Levels and Treatment Response in Major Depressive Disorder (COMPLETED) PHASE4 NCT01369095 — Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression (COMPLETED) PHASE2 NCT01198795 — Safety Study of Escitalopram in Children 7 to 11 Years of Age With Major Depressive Disorder (COMPLETED) PHASE4 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial (JAMA network open, 2020) Clinical trial publication Neuronavigation-Guided rTMS for the Treatment of Depressive Patients With Suicidal Ideation: A Double-Blind, Randomized, Sham-Controlled Trial (Clinical pharmacology and therapeutics, 2020) Clinical trial publication Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial (Journal of affective disorders, 2019) Clinical trial publication Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial (JAMA otolaryngology-- head & neck surgery, 2013) Clinical trial publication Toward a neuroimaging treatment selection biomarker for major depressive disorder (JAMA psychiatry, 2013) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
LEVOMILNACIPRAN HYDROCHLORIDE	Small molecule	Approved	Strong	100	3 trials View evidence Registry trials NCT07253207 — Efficacy and Safety Study of Levomilnacipran Hydrochloride Extended-Release Capsules in Major Depressive Disorder (COMPLETED) PHASE3 NCT01488266 — Aripiprazole Augmentation Versus Switching to Different Class of Antidepressants in Major Depressive Disorder (UNKNOWN) NA NCT00225511 — Study Evaluating Effexor XR for Major Depression. (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Approved	Strong	100	8 trials 22 Cochrane 46 Meta-analysis 103 Trial pubs 75 RCT View evidence Registry trials NCT01962753 — Depression in the Elderly and Cerebral Amyloid Plaques: Characterization by [18F] AV-45 Affectives Symptoms and Amyloïd Plaques (ASAP) (COMPLETED) NA NCT00590863 — Combining Medications to Enhance Depression Outcomes (COMPLETED) PHASE4 NCT02441387 — Predictors of the Outcome of Late Life Depression (UNKNOWN) NCT06309472 — Trial of Mirtazapine for Depression in IBD (RECRUITING) PHASE2 NCT00926835 — Effect of Antidepressants on the Treatment for Korean Major Depressive Disorder Patients (TERMINATED) PHASE4 NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT02458690 — eIMPACT Trial: Modernized Collaborative Care to Reduce the Excess CVD Risk of Older Depressed Patients (COMPLETED) PHASE2 NCT00021528 — Sequenced Treatment Alternatives to Relieve Depression (STARD) (COMPLETED) PHASE4 Published literature* Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Antidepressants for the treatment of depression in people with cancer (The Cochrane database of systematic reviews, 2023) Cochrane review The risks of adverse events with venlafaxine and mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder: a protocol for two separate systematic reviews with meta-analysis and Trial Sequential Analysis (Systematic reviews, 2023) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Cochrane review Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression (Journal of psychopharmacology (Oxford, England), 2023) Meta-analysis Clinical Potential of Mirtazapine in Anxiety and Trauma-Related Disorders: A Systematic Review and Meta-Analysis of Current Evidence (Human psychopharmacology, 2026) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis The risks of adverse events with mirtazapine for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis (BMC psychiatry, 2025) Systematic review The Efficacy of Pharmacological Treatment of Depression in Anorexia Nervosa and Underweight Patients: A Systematic Review (European eating disorders review : the journal of the Eating Disorders Association, 2026) Clinical trial publication Measurement-Based Care to Enhance Antidepressant Treatment Outcomes in Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2025) Clinical trial publication Consistent differential effects of bupropion and mirtazapine in major depression (Journal of affective disorders, 2025) Clinical trial publication Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study (Psychoneuroendocrinology, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
OLANZAPINE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
PAROXETINE	Small molecule	Approved	Strong	100	8 trials 33 Cochrane 59 Meta-analysis 201 Trial pubs 155 RCT View evidence Registry trials NCT00457106 — A Single-Blind Trial of Risperidone vs. Paroxetine for Treatment of Panic Attacks (COMPLETED) NA NCT00519012 — Benefits of Switching Antidepressants Following Early Nonresponse (UNKNOWN) PHASE4 NCT00385307 — Efficacy and Safety of SR58611A in Patients With Major Depressive Disorder (SIRIUS) (COMPLETED) PHASE3 NCT00048607 — Treatment of Patients With Major Depressive Disorder With MK0869 (0869-062)(COMPLETED) (COMPLETED) PHASE3 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00825058 — Efficacy and Safety of SR58611 Compared to Placebo and Paroxetine (COMPLETED) PHASE3 NCT00206765 — Risperidone vs. Paroxetine for Panic Attacks (TERMINATED) PHASE2 NCT01838681 — Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment (COMPLETED) PHASE3 Published literature Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis (BMJ open, 2025) Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review (BMC psychiatry, 2025) Cochrane review The effect of paroxetine on heart rate variability in patients with major depressive disorder: A systematic review and meta-analysis (Journal of affective disorders, 2024) Cochrane review Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis (Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 2022) Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (Molecular psychiatry, 2023) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Efficacy and Safety of Agomelatine in Depressed Patients with Diabetes: A Systematic Review and Meta-Analysis (International journal of molecular sciences, 2024) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Systematic review Subgenual anterior cingulate cortex and antidepressant response to serotonergic and glutamatergic pharmacological treatments: a systematic review of neuroimaging studies (Progress in neuro-psychopharmacology & biological psychiatry, 2026) Clinical trial publication Measurement-Based Care to Enhance Antidepressant Treatment Outcomes in Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2025) Clinical trial publication Interpersonal sensitivity and response to selective serotonin reuptake inhibitors in patients with acute major depressive disorder (Journal of affective disorders, 2024) Clinical trial publication Artificial intelligence approach for the analysis of placebo-controlled clinical trials in major depressive disorders accounting for individual propensity to respond to placebo (Translational psychiatry, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
PAROXETINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUETIAPINE FUMARATE	Small molecule	Approved	Strong	100	8 trials 20 Trial pubs 20 RCT View evidence Registry trials NCT00388973 — Efficacy and Safety Study of Seroquel SR in the Treatment of Major Depressive Disorder (COMPLETED) PHASE3 NCT00321490 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo and Active Control in Major Depressive Disorder (COMPLETED) PHASE3 NCT02720198 — Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD (COMPLETED) PHASE3 NCT00892463 — Identifying Very Early Response to Seroquel Extended Release (XR) Augmentation for Major Depressive Disorder (COMPLETED) PHASE4 NCT01795326 — Physician Survey on Monitoring of Patients Treated With Quetiapine (COMPLETED) NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT00955474 — Seroquel Alone Versus Seroquel With an SSRI for Depression With Psychotic Symptoms (TERMINATED) PHASE4 NCT00320268 — Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo in Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication Analysis of potentially predictive factors of efficacy of adjunct extended-release quetiapine fumarate in patients with major depressive disorder (Journal of psychopharmacology (Oxford, England), 2015) Clinical trial publication The influence of Hatha yoga as an add-on treatment in major depression on hypothalamic-pituitary-adrenal-axis activity: a randomized trial (Journal of psychiatric research, 2014) Clinical trial publication Extended release quetiapine fumarate as adjunct to antidepressant therapy in patients with major depressive disorder: pooled analyses of data in patients with anxious depression versus low levels of anxiety at baseline (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2014) Clinical trial publication Quetiapine fumarate extended-release for the treatment of major depression with comorbid fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study (Arthritis & rheumatology (Hoboken, N.J.), 2014) Clinical trial publication Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression (Psychoneuroendocrinology, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
SERTRALINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 9 Trial pubs 9 RCT View evidence Registry trials NCT05002309 — Treatment Interrupts Depression Early (RECRUITING) PHASE2 NCT00519012 — Benefits of Switching Antidepressants Following Early Nonresponse (UNKNOWN) PHASE4 NCT00177996 — Pharmacotherapy in Depression With Panic Spectrum (COMPLETED) PHASE4 NCT07478796 — TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children (RECRUITING) PHASE4 NCT01838876 — Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00174590 — Treatment of Major Depressive Disorder With Psychotic Features. (TERMINATED) PHASE3 NCT07015944 — Moving on After Breast Cancer Trial for Depressed Breast Cancer Survivors in Pakistan (RECRUITING) NA NCT00275197 — A Research Study to Compare the Treatments of a Combination of Elzasonan With Zoloft, to Zoloft Alone, or Placebo in People With Major Depressive Disorder (MDD) (COMPLETED) PHASE2 Published literature Clinical trial publication Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial (JAMA network open, 2020) Clinical trial publication Cortical Connectivity Moderators of Antidepressant vs Placebo Treatment Response in Major Depressive Disorder: Secondary Analysis of a Randomized Clinical Trial (JAMA psychiatry, 2020) Clinical trial publication Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial (JAMA psychiatry, 2018) Clinical trial publication The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial (JAMA psychiatry, 2013) Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features (Archives of general psychiatry, 2008) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT04295941 — Long-term Study With Trazodone Once-a-Day (COMPLETED) NCT07210112 — Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ) (NOT_YET_RECRUITING) PHASE2 NCT01764867 — Algorithm Guided Treatment Strategies for Major Depressive Disorder (UNKNOWN) PHASE4 NCT00704860 — Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (COMPLETED) PHASE4 NCT00775203 — A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder. (COMPLETED) PHASE3 NCT07377682 — Real-world Clinical Response to Trazodone in Italy, Poland, and Romania (RECRUITING) NCT05889234 — Multimodal Magnetic Resonance Imaging-based Study of Electroconvulsive Efficacy Prediction in Adolescents With Depression: a Multicenter Prospective Cohort Study (UNKNOWN) NCT07328373 — Neurobiological and Genomic Predictors of Relapse in Depression (RECRUITING) Published literature Clinical trial publication The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder (Psychopharmacology bulletin, 2009) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
VENLAFAXINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMIBEGRON	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
APREPITANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CARIPRAZINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CELECOXIB	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXMECAMYLAMINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROMETHORPHAN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
EDIVOXETINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ICOSAPENT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
INSULIN HUMAN	Biologic	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
KETAMINE HYDROCHLORIDE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
LISDEXAMFETAMINE DIMESYLATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MEMANTINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
METHYLPHENIDATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MIFEPRISTONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MINOCYCLINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
MODAFINIL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIPAMPERONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
PSILOCYBIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
RISPERIDONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SAREDUTANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ARMODAFINIL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ATICAPRANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
AZETUKALNER	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
BEFLOXATONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
BUPRENORPHINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
CHEMBL10316	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200574	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL4084119	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CLOZAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DOCONEXENT	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESMETHADONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ESZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
FEMOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
FLUOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
HALOPERIDOL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
INDIPLON	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
KETAMINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LIOTHYRONINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LITHIUM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LUMATEPERONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LURASIDONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MIDAZOLAM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NALOXONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NAVACAPRANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NOREPINEPHRINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
OLSALAZINE SODIUM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
OMEGA-3 FATTY ACIDS	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
PIMAVANSERIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
PRAMIPEXOLE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
QUETIAPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
RAPASTINEL	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ROFLUMILAST	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ROSUVASTATIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SAMIDORPHAN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SELTOREXANT	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SEROTONIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SIMVASTATIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
SOLRIAMFETOL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VALPROIC ACID	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VORTIOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ACETYLCYSTEINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ADEMETIONINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMITIFADINE HYDROCHLORIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CLAVULANIC ACID	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CYCLOSERINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXTROMETHORPHAN HYDROBROMIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
EZOGABINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
FARAMPATOR	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABOXADOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LANICEMINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LEUCINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LOSMAPIMOD	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LYSERGIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
METYRAPONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NALUZOTAN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NIACIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NITROUS OXIDE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
OMEGA-3-ACID ETHYL ESTERS	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ONABOTULINUMTOXINA	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ORVEPITANT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
OXYTOCIN	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PENTOXIFYLLINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PINDOLOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUINIDINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
REBOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
RILUZOLE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SIRUKUMAB	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TASIMELTEON	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TEDATIOXETINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
TOCILIZUMAB	Biologic	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
VERUCERFONT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
(+/-)NICOTINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ABX-002	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ACAMPROSATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ADENOSINE TRIPHOSPHATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALLOPURINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AMITIFADINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
APIMOSTINEL	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ATORVASTATIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AV-101	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AZD-7268	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AZD2066	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BARICITINIB	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BASIMGLURANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BREZIVAPTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BUSPIRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CASOPITANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CENTANAFADINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CERONAPRIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1200420	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1715	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107951	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL2108243	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL25	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL451	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL521	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CLEMASTINE FUMARATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CP-601927	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CREATINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CRINECERFONT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CX-157	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DAPAGLIFLOZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DASATINIB	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DASOTRALINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DECOGLURANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DEXMECAMYLAMINE HYDROCHLORIDE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DIPHENHYDRAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DU 125530	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ELZASONAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EMESTEDASTAT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EMPAGLIFLOZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ESUPRONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
EVT-101	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FILOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FISH OIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FOSFOCREATINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
GSK163090	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
HYDROXYNORKETAMINE, (2R,6R)	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ICALCAPRANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
IGMESINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-18038683	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-26489112	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-39393406	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-40411813	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-42165279	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
JNJ-54175446	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LEVODOPA	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LIAFENSINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LY-2940094	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LY2940094	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MAGNESIUM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MANIFAXINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MECAMYLAMINE	Small molecule	Phase II	Emerging	60	8 trials 3 Trial pubs 2 RCT View evidence Registry trials NCT01180400 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT01288079 — A Study to Assess the Safety and Effect of TC-5214 in Patients With Major Depressive Disorder. (TERMINATED) PHASE2 NCT01197508 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder. (COMPLETED) PHASE3 NCT01152554 — A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00319319 — Nicotinic Receptor Augmentation of SSRI Antidepressants (COMPLETED) PHASE2 NCT00692445 — TC-5214 as add-on the Treatment of Major Depressive Disorder (COMPLETED) PHASE2 NCT01157078 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT01153347 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD) (ACS chemical neuroscience, 2010) Clinical trial publication Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study (Journal of clinical psychopharmacology, 2008) Clinical trial publication Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamine (Depression and anxiety, 2002) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
MECAMYLAMINE HYDROCHLORIDE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MELATONIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MK-8777	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
N,N-DIMETHYLTRYPTAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NAPITANE MESYLATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NELIVAPTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NEMIFITIDE	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NICOTINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NS-2359	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NSI-189	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
NV-5138	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONDANSETRON	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONFASPRODIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ONO-2333MS	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ORG-34517	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PIOGLITAZONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
QUERCETIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
QUINIDINE SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
RADAFAXINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
RISLENEMDAZ	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ROPANICANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SARCOSINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SCOPOLAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SELENIUM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SEMAGLUTIDE	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM BENZOATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM LACTATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SOY ISOFLAVONES	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SULFORAPHANE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SURITOZOLE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SUVOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TEBIDEUTOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TRAMADOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TRAXOPRODIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ULOTARONT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VESTIPITANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
VOLINANSERIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
YOHIMBINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZELATRIAZIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZELQUISTINEL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ZIPRASIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
AMISULPRIDE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
METFORMIN	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PERAMPANEL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PEXACERFONT	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PROPOFOL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMPHETAMINE	Small molecule	Phase I	Emerging	35	8 trials 2 Trial pubs 2 RCT View evidence Registry trials NCT02058693 — Adjunctive Mixed Salts Amphetamine for Depressed Adults With Incomplete Response to Current Antidepressant Therapy (COMPLETED) PHASE4 NCT06967857 — Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression (RECRUITING) PHASE2 NCT00985725 — SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder (COMPLETED) PHASE2 NCT00296686 — Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression (TERMINATED) PHASE4 NCT01435759 — SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE2 NCT01436162 — Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE3 NCT01148979 — Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder. (COMPLETED) PHASE4 NCT00905424 — Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant (COMPLETED) PHASE2 Published literature Systematic review Navigating the challenges of substance use and psychopathology in depression, bipolar disorder, and schizophrenia (Comprehensive psychiatry, 2025) Systematic review Amphetamine Use in the Elderly: A Systematic Review of the Literature (Current neuropharmacology, 2020) Clinical trial publication Longitudinal study of impact of medication for opioid use disorder on Hamilton Depression Rating Scale (Journal of affective disorders, 2022) Clinical trial publication Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (Journal of affective disorders, 2016) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
BACLOFEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
BOTULINUM TOXIN TYPE A	Biologic	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
BRILAROXAZINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
CHEMBL1355736	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1741	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL1751	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2103774	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL2106049	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL545	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL63	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL714	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
DIAZOXIDE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
FOSIGOTIFATOR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
GSK1360707	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
HT-2157	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
HYDROCORTISONE ACETATE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
KETOPROFEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
MEMANTINE HYDROCHLORIDE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
MGS-0210	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
PF-04995274	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
PREGNENOLONE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
SALMONELLA TYPHI TY2 VI POLYSACCHARIDE ANTIGEN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TADALAFIL	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TOFACITINIB	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
TOLUDESVENLAFAXINE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
VALGANCICLOVIR	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
VILDAGLIPTIN	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
XENON	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
ZOLPIDEM	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
(+)-TRANYLCYPROMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ALAPROCLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMINEPTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMITRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMITRIPTYLINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
AMOXAPINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BETAINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BIFEMELANE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BREXANOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUPROPION	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUPROPION HYDROBROMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CALCIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CENTANAFADINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL142438	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CHOLINE ALFOSCERATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CILOSTAZOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CITICOLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLOMIPRAMINE	Small molecule	Preclinical	Emerging	15	5 trials 6 Cochrane 8 Meta-analysis 20 Trial pubs 14 RCT View evidence Registry trials NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT00944996 — Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression (COMPLETED) NA NCT01944657 — Supplemental Transcranial Magnetic Stimulation (TMS) vs. Standard Medication Monotherapy for Treating Major Depression: An Exploratory Field Study (WITHDRAWN) NA NCT00704860 — Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (COMPLETED) PHASE4 NCT05952713 — Comparative Responses to 15 Different Antidepressants in Major Depressive Disorder (COMPLETED) Published literature Cochrane review Efficacy and dose-response relationships of antidepressants in the acute treatment of major depressive disorders: a systematic review and network meta-analysis (Chinese medical journal, 2025) Cochrane review Tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis (Systematic reviews, 2021) Cochrane review Beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses (Systematic reviews, 2021) Cochrane review Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic review (Progress in neuro-psychopharmacology & biological psychiatry, 2019) Cochrane review Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis (Lancet (London, England), 2018) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Meta-analysis Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis (Lancet (London, England), 2016) Clinical trial publication Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2023) Clinical trial publication Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration (CNS spectrums, 2019) Clinical trial publication Are antidepressants equally effective in the long-term treatment of major depressive disorder? (Human psychopharmacology, 2015) Clinical trial publication The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine (Journal of affective disorders, 2012) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
CLOVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CYSTEAMINE BITARTRATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESIPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESIPRAMINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESVENLAFAXINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DESVENLAFAXINE FUMARATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DEXAMETHASONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIBENZEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIMETACRINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIVALPROEX SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOTHIEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOXEPIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DOXEPIN HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DULOXETINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESKETAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESKETAMINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETOPERIDONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FISH OIL TRIGLYCERIDES	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUDROCORTISONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUOXETINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GANAXOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEMIBOTULINUMTOXIN A	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEPIRONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GEPIRONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GHRELIN	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GOLIMUMAB	Biologic	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GR-127935	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GW 3965	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IMIPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IMIPRAMINOXIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPRINDOLE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPROCLOZIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
IPRONIAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ISOCARBOXAZID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LAMOTRIGINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LEVOMEFOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LEVOMILNACIPRAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LIOTHYRONINE SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LITHIUM CARBONATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LOFEPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LORAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAPROTILINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAPROTILINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MEDIFOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MELITRACEN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MIANSERIN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MILNACIPRAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MINAPRINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MOCLOBEMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NALOXONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NEFAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NEFAZODONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NIALAMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NOMIFENSINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NORTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NORTRIPTYLINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OPIPRAMOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OXAFLOZANE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OXITRIPTAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PAROXETINE MESYLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PHENELZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PIVAGABINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PIZOTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PROTRIPTYLINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
QUINUPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
RAMELTEON	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ROPINIROLE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SELEGILINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SERTRALINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SILDENAFIL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SODIUM CITRATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ST. JOHN'S WORT	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
SULPIRIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TESTOSTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TIANEPTINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TOLOXATONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TOLUDESVENLAFAXINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRANYLCYPROMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRANYLCYPROMINE SULFATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRIMIPRAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRYPTOPHAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TYROSINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ULOTARONT HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE BESYLATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILAZODONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILAZODONE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VILOXAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VORTIOXETINE HYDROBROMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZIMELDINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZINC SULFATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ZURANOLONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACEBUTOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ALFUZOSIN Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
ALFUZOSIN HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AMIODARONE HYDROCHLORIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
AMITRIPTYLINE HYDROCHLORIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	8 trials 2 Trial pubs 2 RCT View evidence Registry trials NCT02058693 — Adjunctive Mixed Salts Amphetamine for Depressed Adults With Incomplete Response to Current Antidepressant Therapy (COMPLETED) PHASE4 NCT06967857 — Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression (RECRUITING) PHASE2 NCT00985725 — SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder (COMPLETED) PHASE2 NCT00296686 — Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression (TERMINATED) PHASE4 NCT01435759 — SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE2 NCT01436162 — Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (COMPLETED) PHASE3 NCT01148979 — Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder. (COMPLETED) PHASE4 NCT00905424 — Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant (COMPLETED) PHASE2 Published literature Systematic review Navigating the challenges of substance use and psychopathology in depression, bipolar disorder, and schizophrenia (Comprehensive psychiatry, 2025) Systematic review Amphetamine Use in the Elderly: A Systematic Review of the Literature (Current neuropharmacology, 2020) Clinical trial publication Longitudinal study of impact of medication for opioid use disorder on Hamilton Depression Rating Scale (Journal of affective disorders, 2022) Clinical trial publication Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (Journal of affective disorders, 2016) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
APOMORPHINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASENAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CARVEDILOL PHOSPHATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
CELIPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORMERODRIN Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORPROMAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
CLOMIPRAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	5 trials 6 Cochrane 8 Meta-analysis 20 Trial pubs 14 RCT View evidence Registry trials NCT01305707 — Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression (TERMINATED) PHASE4 NCT00944996 — Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression (COMPLETED) NA NCT01944657 — Supplemental Transcranial Magnetic Stimulation (TMS) vs. Standard Medication Monotherapy for Treating Major Depression: An Exploratory Field Study (WITHDRAWN) NA NCT00704860 — Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (COMPLETED) PHASE4 NCT05952713 — Comparative Responses to 15 Different Antidepressants in Major Depressive Disorder (COMPLETED) Published literature Cochrane review Efficacy and dose-response relationships of antidepressants in the acute treatment of major depressive disorders: a systematic review and network meta-analysis (Chinese medical journal, 2025) Cochrane review Tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis (Systematic reviews, 2021) Cochrane review Beneficial and harmful effects of antidepressants versus placebo, 'active placebo', or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses (Systematic reviews, 2021) Cochrane review Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic review (Progress in neuro-psychopharmacology & biological psychiatry, 2019) Cochrane review Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis (Lancet (London, England), 2018) Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis (Translational psychiatry, 2025) Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis (Andrology, 2025) Meta-analysis Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis (Lancet (London, England), 2016) Clinical trial publication Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial (JAMA network open, 2023) Clinical trial publication Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration (CNS spectrums, 2019) Clinical trial publication Are antidepressants equally effective in the long-term treatment of major depressive disorder? (Human psychopharmacology, 2015) Clinical trial publication The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine (Journal of affective disorders, 2012) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
CLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CLOZAPINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
CYCLOBENZAPRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CYPROHEPTADINE HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
DAPIPRAZOLE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
DAPIPRAZOLE HYDROCHLORIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DEBRISOQUIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DISULFIRAM Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIVALPROEX SODIUM Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DOPAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DRONEDARONE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE Repurposing via ADRA1D	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
GUANABENZ Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
IMIPRAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDAPAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ISOPROTERENOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LEVETIRACETAM Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
LEVONORDEFRIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LISDEXAMFETAMINE DIMESYLATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LURASIDONE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MECAMYLAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	8 trials 3 Trial pubs 2 RCT View evidence Registry trials NCT01180400 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT01288079 — A Study to Assess the Safety and Effect of TC-5214 in Patients With Major Depressive Disorder. (TERMINATED) PHASE2 NCT01197508 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder. (COMPLETED) PHASE3 NCT01152554 — A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 NCT00319319 — Nicotinic Receptor Augmentation of SSRI Antidepressants (COMPLETED) PHASE2 NCT00692445 — TC-5214 as add-on the Treatment of Major Depressive Disorder (COMPLETED) PHASE2 NCT01157078 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD) (COMPLETED) PHASE3 NCT01153347 — A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (COMPLETED) PHASE3 Published literature Clinical trial publication (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD) (ACS chemical neuroscience, 2010) Clinical trial publication Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study (Journal of clinical psychopharmacology, 2008) Clinical trial publication Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamine (Depression and anxiety, 2002) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METARAMINOL Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
METARAMINOL BITARTRATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHADONE HYDROCHLORIDE Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAMPHETAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOTRIMEPRAZINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
METHOXAMINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
METHOXAMINE HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHOXSALEN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METOPROLOL SUCCINATE Repurposing via ADRA1D	Small molecule	Approved	Strong	95	—	DGIdb	—
MIANSERIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MIDODRINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
MIDODRINE HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
MILNACIPRAN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MODAFINIL Repurposing via ADRA1D	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NAFTOPIDIL Repurposing via ADRA1D	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NALIDIXIC ACID Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NAPHAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NEFAZODONE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
NICOTINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NIFEDIPINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORFLOXACIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PAPAVERINE Repurposing via ADRA1D	Small molecule	Approved	Strong	95	—	DGIdb	—
PERGOLIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENDIMETRAZINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLEPHRINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYLEPHRINE BITARTRATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLEPHRINE HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYLPROPANOLAMINE HYDROCHLORIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE POLISTIREX Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYTOIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PHENYTOIN SODIUM Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
PINDOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PRAZOSIN HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PROMAZINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPIOMAZINE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPRANOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPYLHEXEDRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
QUETIAPINE FUMARATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
SERTINDOLE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
SILODOSIN Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
SODIUM OXYBATE Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
SUCCINIC ACID Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAMSULOSIN HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
TAMSULOSIN HYDROCHLORIDE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TAZOBACTAM Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TERAZOSIN Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
TERAZOSIN HYDROCHLORIDE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
THIORIDAZINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIFLUOPERAZINE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIMIPRAMINE MALEATE Repurposing via ADRA1B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TROGLITAZONE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
VALPROATE SODIUM Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
VALPROIC ACID Repurposing via ALDH5A1	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ZIPRASIDONE Repurposing via ADRA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
DARAPLADIB Repurposing via ADRA1A	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing via ADRA1A	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
ALPRENOLOL Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing via ADRA1A	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Curcumin OSMF review	Nutraceutical	Preclinical	Emerging	30	2 trials 2 Meta-analysis 9 Trial pubs 8 RCT View evidence Registry trials NCT01750359 — Efficacy and Safety Curcumin in Depression (COMPLETED) PHASE4 NCT01022632 — Effect of Curcumin as Nutraceutical in Patients of Depression (COMPLETED) NA Published literature Meta-analysis Curcumin for depression: a meta-analysis (Critical reviews in food science and nutrition, 2020) Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials (Phytotherapy research : PTR, 2016) Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication Tetrahydrocurcumin for Major Depressive Disorder with Therapeutic Potential and Mechanistic Insights from Clinical and Preclinical Studies (Molecular neurobiology, 2025) Clinical trial publication Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study (Neurotoxicity research, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) Clinical trial publication Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study (Journal of clinical psychopharmacology, 2015) Clinical trial publication Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2015) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Ibogaine OSMF review	Psychedelic	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Ketamine (Esketamine) OSMF review	Small molecule	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
MDMA-assisted therapy OSMF review	Psychedelic	Preclinical	Emerging	30	—	OSMF Chronic Disease Review	OSMF Review Citation
Magnesium OSMF review	Supplement	Preclinical	Emerging	30	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT07633080 — Magnesium Bisglycinate in Major Depressive Disorder (RECRUITING) NA NCT00797966 — Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder (COMPLETED) PHASE2 NCT07458022 — MAGNESIUM & SSRI VS SSRI ALONE AMONG PATIENTS OF MAJOR DEPRESSIVE DISORDER (ACTIVE_NOT_RECRUITING) PHASE2 NCT07198477 — Sleep Disturbances and Their Association With Serum Magnesium Level in Patients With Major Depressive Disorder (NOT_YET_RECRUITING) NCT03877393 — The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (UNKNOWN) NA NCT07521358 — Magnesium Supplementation With Fluoxetine for Cognitive Function in Depression (COMPLETED) NA NCT01941043 — A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment (COMPLETED) PHASE2 NCT04880460 — Effect of Magnesium Supplementation in Selective Serotonin Reuptake Inhibitors Treated Major Depressive Disorder Patients (COMPLETED) PHASE2 Published literature Clinical trial publication Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial (Scientific reports, 2024) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Omega-3 fatty acids (EPA/DHA) OSMF review	Supplement	Preclinical	Emerging	30	8 trials View evidence Registry trials NCT00816322 — The Effect of Fish Oil in Major Depressive Disorder (COMPLETED) NA NCT05774665 — Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression (ACTIVE_NOT_RECRUITING) PHASE2 NCT00618865 — Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy (COMPLETED) NA NCT00517036 — Omega-3 Fatty Acids for Treating Adults With Major Depression (COMPLETED) PHASE3 NCT01620502 — N-3 Polyunsaturated Fatty Acids in the Prevention and Treatment for IFN-induced Depression (COMPLETED) NA NCT03072823 — Omega-3 Polyunsaturated Fatty Acids on Major Depressive Disorder in Patients With Cardiovascular Diseases (COMPLETED) NA NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT00361374 — Safety and Effectiveness of Omega 3-Fatty Acids, EPA Versus DHA, for the Treatment of Major Depression (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Psilocybin OSMF review	Psychedelic	Preclinical	Emerging	30	8 trials 8 Cochrane 12 Meta-analysis 33 Trial pubs 25 RCT View evidence Registry trials NCT05434156 — ELE-101 Safety & Tolerability Study in Healthy Participants and Patients With Depression (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT06308653 — Psilocybin for Major Depressive Disorder (MDD) (ACTIVE_NOT_RECRUITING) PHASE3 NCT06624137 — Computer Game, Qualitative, and MEG/EEG Assessment of Serotonergic Psychedelics (RECRUITING) NCT05381974 — The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD (WITHDRAWN) PHASE2 NCT05399498 — Psilocybin in Co-occuring Major Depressive Disorder and Borderline Personality Disorder (COMPLETED) PHASE2 NCT05259943 — Microdosing Psychedelics to Improve Mood (COMPLETED) PHASE2 NCT06141876 — Evaluation of Psilocybin-Assisted Psychotherapy in Treating Severe Depression in Patients With PTSD (UNKNOWN) PHASE2 NCT03181529 — Effects of Psilocybin in Major Depressive Disorder (COMPLETED) PHASE2 Published literature Cochrane review Therapeutic effects of psilocybin in major depressive disorder: a systematic review and meta-analysis exploring dose effects (European archives of psychiatry and clinical neuroscience, 2026) Cochrane review Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials (Psychiatry research, 2025) Cochrane review Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis (Acta psychiatrica Scandinavica, 2025) Cochrane review Psilocybin for major depressive disorder: An updated systematic review and meta-analysis of randomized clinical trials (Journal of psychopharmacology (Oxford, England), 2026) Cochrane review [Treatment-resistant depression. From classification to new therapies.] (Rivista di psichiatria, 2022) Meta-analysis Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis (Journal of affective disorders, 2026) Meta-analysis Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis (Neuroscience and biobehavioral reviews, 2026) Meta-analysis Breaking the chains of depression: A systematic review and meta-analysis of psilocybin therapy (Journal of affective disorders, 2026) Meta-analysis Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis (JAMA network open, 2025) Systematic review Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal (Journal of affective disorders, 2026) Clinical trial publication Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial (JAMA network open, 2026) Clinical trial publication Evaluation of a facilitator training program in a randomized controlled trial of psilocybin treatment for depression (BMC medical education, 2026) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
SAMe (S-adenosylmethionine) OSMF review	Supplement	Preclinical	Emerging	30	4 trials View evidence Registry trials NCT04832178 — Sumor as Adjuvant Therapy in Treatment-resistant Major Depression (UNKNOWN) PHASE4 NCT01912196 — Add-On Study of MSI-195 (S-Adenosyl-L-Methionine, SAMe) for Patients With Major Depressive Disorder (MDD) (COMPLETED) PHASE2 NCT00101452 — Safety and Effectiveness of S-adenosyl-l-methionine (SAMe) for the Treatment of Major Depression (COMPLETED) NA NCT04623034 — Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Saffron (Crocus sativus) OSMF review	Herbal	Preclinical	Emerging	30	1 Meta-analysis 4 Trial pubs 4 RCT View evidence Published literature Meta-analysis Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials (Journal of integrative medicine, 2013) Systematic review A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes (Journal of integrative medicine, 2015) Clinical trial publication Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial (Pharmacopsychiatry, 2017) Clinical trial publication Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial (Journal of affective disorders, 2015) Clinical trial publication Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study (Human psychopharmacology, 2013) Clinical trial publication Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial (Psychopharmacology, 2012) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
St. John's Wort (Hypericum perforatum) OSMF review	Herbal	Preclinical	Emerging	30	4 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT00005013 — Treatment of Major Depression With St. John's Wort (Hypericum) (COMPLETED) NA NCT04315597 — Study to Learn About Relapse Prevention of Hypericumextract (a Drug Based on the Plant St. John Wort) in Outpatients Suffering From Moderate Depressive Episodes (COMPLETED) PHASE3 NCT00451516 — St. John's Wort And Kava In The Treatment Of Major Depressive Disorder With Comorbid Anxiety (COMPLETED) PHASE2 NCT05477472 — Low Dose St John's Wort for Depression (COMPLETED) Published literature Clinical trial publication St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT (Pharmacopsychiatry, 2012) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation
Vitamin D OSMF review	Supplement	Preclinical	Emerging	30	7 trials 2 Cochrane 4 Meta-analysis 11 Trial pubs 10 RCT View evidence Registry trials NCT04898725 — Effects of Vitamin D Supplementation on Depression and Inflammatory Markers (COMPLETED) NA NCT01390662 — Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression (UNKNOWN) PHASE4 NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT01932931 — Vitamin D, SSRIs and the Musculoskeletal System (COMPLETED) NA NCT03754712 — Effect of Vitamin D Administration Along With SSRIs in Patients With Major Depressive Disorder (UNKNOWN) NA NCT07579078 — Effect of Vitamin D Supplementation on Brain Waves in Female Major Depressive Disorder Patients With Hypovitaminosis D (ENROLLING_BY_INVITATION) NA NCT00005119 — Altered Calcium and Vitamin D in PMDD or Severe PMS (COMPLETED) NA Published literature Cochrane review Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials (Nutrition (Burbank, Los Angeles County, Calif.), 2023) Cochrane review Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials (Journal of postgraduate medicine, 2019) Meta-analysis Genome-wide interaction study with major depression identifies novel variants associated with cognitive function (Molecular psychiatry, 2022) Meta-analysis The effect of vitamin D supplement on negative emotions: A systematic review and meta-analysis (Depression and anxiety, 2020) Systematic review Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials (Nutritional neuroscience, 2023) Systematic review Nutrient and genetic biomarkers of nutraceutical treatment response in mood and psychotic disorders: a systematic review (Nutritional neuroscience, 2021) Clinical trial publication Do probiotics modulate dietary intake? Pilot data from a randomized controlled sub-study of the ProBioHRV clinical trial in patients with depression and healthy controls (PloS one, 2026) Clinical trial publication Effect of a six-month vitamin D supplementation on depressive symptoms in patients with major depressive episode (DepFuD): a double-blinded randomised controlled trial (Journal of affective disorders, 2026) Clinical trial publication Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trial (Clinical nutrition (Edinburgh, Scotland), 2026) Clinical trial publication The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial (Psychological medicine, 2024) Clinical trial publication Effects of Vitamin D(3) and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL) (The Journal of clinical psychiatry, 2023) CT.gov search · Cochrane · PubMed	OSMF Chronic Disease Review	OSMF Review Citation

Natural Products

141 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked)

Reference lookups: GreenMedInfo · Examine.com

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Probiotics Natural product Meta Analysis Altering the gut-brain axis with probiotics may be an approach to impro… Meta Analysis, Review There is general support for antidepressant and anxiolytic effects of p… Animal Study, Human Study Assessment of psychotropic-like properties of a probiotic formulation (…	Probiotic	Phase III	Moderate	26	8 trials 20 Trial pubs View evidence Registry trials NCT06790823 — Effect of Probiotic Supplement on Improvement of Depressive Symptoms in Patients With Substance-Induced Depressive Disorder (COMPLETED) PHASE1, PHASE2 NCT05315401 — The Efficacy of Probiotic Compared With Placebo Commitment Therapy for Treatment of Major Depressive Disorder (WITHDRAWN) PHASE2 NCT03237078 — Lactobacillus Plantarum PS128 in Patients With Major Depressive Disorder and High Level of Inflammation (UNKNOWN) NA NCT04333277 — Lactobacillus Helveticus in the Treatment of Major Depression (UNKNOWN) NA NCT05280015 — Microbiotherapy in Characterized Depressive Disorder (UNKNOWN) PHASE2 NCT03877393 — The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (UNKNOWN) NA NCT02838043 — The Efficacy, Safety, and Tolerability of Probiotics on the Mood and Cognition of Depressed Patients (COMPLETED) PHASE3 NCT02957591 — Probiotic Supplementation in Severe Depression (COMPLETED) NA CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com, GreenMedInfo	Examine.com GreenMedInfo
Vitamin D3 Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results demonstrate that vitamin D has a beneficial impact on bot… Meta Analysis This meta-analysis suggests that increasing 25(OH)D levels may be a use…	Nutraceutical	Approved	Moderate	20	6 trials 3 Trial pubs 3 RCT View evidence Registry trials NCT04898725 — Effects of Vitamin D Supplementation on Depression and Inflammatory Markers (COMPLETED) NA NCT00005119 — Altered Calcium and Vitamin D in PMDD or Severe PMS (COMPLETED) NA NCT01932931 — Vitamin D, SSRIs and the Musculoskeletal System (COMPLETED) NA NCT03754712 — Effect of Vitamin D Administration Along With SSRIs in Patients With Major Depressive Disorder (UNKNOWN) NA NCT07579078 — Effect of Vitamin D Supplementation on Brain Waves in Female Major Depressive Disorder Patients With Hypovitaminosis D (ENROLLING_BY_INVITATION) NA NCT01390662 — Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression (UNKNOWN) PHASE4 CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Magnesium Natural product Meta Analysis Dietary magnesium intake was significantly associated with a reduced ri… Human Study A 6-month follow-up of disability, quality of life, and depressive and… Human Study A combination of probiotics and magnesium orotate attenuate depression.	Nutraceutical	Approved	Moderate	20	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT04880460 — Effect of Magnesium Supplementation in Selective Serotonin Reuptake Inhibitors Treated Major Depressive Disorder Patients (COMPLETED) PHASE2 NCT00797966 — Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder (COMPLETED) PHASE2 NCT07198477 — Sleep Disturbances and Their Association With Serum Magnesium Level in Patients With Major Depressive Disorder (NOT_YET_RECRUITING) NCT03877393 — The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (UNKNOWN) NA NCT07458022 — MAGNESIUM & SSRI VS SSRI ALONE AMONG PATIENTS OF MAJOR DEPRESSIVE DISORDER (ACTIVE_NOT_RECRUITING) PHASE2 NCT01941043 — A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment (COMPLETED) PHASE2 NCT07521358 — Magnesium Supplementation With Fluoxetine for Cognitive Function in Depression (COMPLETED) NA NCT00666757 — A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Vitamin B12 Natural product Clinical trial publication Folate metabolism biomarkers from two randomised placebo-controlled cli… Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major dep… Clinical trial publication B vitamins to enhance treatment response to antidepressants in middle-a…	Nutraceutical	Approved	Moderate	20	5 trials 6 Trial pubs 4 RCT View evidence Registry trials NCT00214682 — Beyond Ageing Project: A Study for the Prevention of Depression (COMPLETED) PHASE2 NCT04832178 — Sumor as Adjuvant Therapy in Treatment-resistant Major Depression (UNKNOWN) PHASE4 NCT01369030 — Deplin® P.L.U.S. Program (Progress Through Learning Understanding & Support) (COMPLETED) NCT07200739 — Speech-Based Artificial Intelligence for Detection of Dementia in Danish Patients (DetectAI) (NOT_YET_RECRUITING) NCT00939718 — Comparison of Vitamin B12 Supplementation to Selective Serotonin Reuptake Inhibitor (SSRI) Versus SSRI Antidepressant Treatment Alone (UNKNOWN) NA Published literature Clinical trial publication Folate metabolism biomarkers from two randomised placebo-controlled clinical studies with paroxetine and venlafaxine (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2021) Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major depressive disorder (European journal of nutrition, 2020) Clinical trial publication B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial (The British journal of psychiatry : the journal of mental science, 2014) Clinical trial publication Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes (Neuroimmunomodulation, 2008) Clinical trial publication The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine (The international journal of neuropsychopharmacology, 2005) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Omega-3 Fatty Acids Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results indicate a beneficial effect of the combination of EPA an…	Nutraceutical	Phase II	Moderate	20	8 trials View evidence Registry trials NCT03732378 — Role of Omega-3 Polyunsaturated Fatty Acid in the Management of Major Depressive Disorder. (COMPLETED) NA NCT00618865 — Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy (COMPLETED) NA NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT00001146 — Omega-3 Fatty Acids in the Treatment of Bipolar Disorder: A Double-Blind, Placebo-Controlled Trial (COMPLETED) PHASE2 NCT00962598 — The Role Of Omega-3 Fatty Acids In Adolescent Depression (COMPLETED) PHASE2 NCT00963196 — Study of Supplementation of Antidepressants With Fish Oil to Improve Time to Clinical Response (WITHDRAWN) NA NCT05389046 — Study on the Optimal Diagnosis and Treatment Strategy of Major Depressive Disorder Based on Anhedonia (UNKNOWN) NA NCT04158869 — An Investigation of the Relationship Between Omega-3 Fatty Acid Nutrition and Mental Health in Children and Adolescents (COMPLETED) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Zinc Natural product Cochrane review Oxidative stress and antioxidant parameters in patients with major depr… Meta-analysis Association between serum levels of essential elements (copper, zinc, a… Meta-analysis Zinc supplementation combined with antidepressant drugs for treatment o…	Nutraceutical	Preclinical	Moderate	20	2 trials 1 Cochrane 3 Meta-analysis 9 Trial pubs 6 RCT View evidence Registry trials NCT00693680 — Zinc Supplementation of Imipramine Therapy (COMPLETED) NA NCT04482296 — Effect of Zinc Supplementation on Depression in SSRI-treated Major Depressive Disorder Patients (COMPLETED) NA Published literature Cochrane review Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis (The Journal of clinical psychiatry, 2015) Meta-analysis Association between serum levels of essential elements (copper, zinc, and iron) and major depressive disorder: a systematic review and meta-analysis (Reviews on environmental health, 2026) Meta-analysis Zinc supplementation combined with antidepressant drugs for treatment of patients with depression: a systematic review and meta-analysis (Nutrition reviews, 2021) Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major depressive disorder (European journal of nutrition, 2020) Clinical trial publication Nutraceuticals for major depressive disorder- more is not merrier: An 8-week double-blind, randomised, controlled trial (Journal of affective disorders, 2019) Clinical trial publication Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial (Pharmacological reports : PR, 2015) Clinical trial publication Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression (Nutritional neuroscience, 2014) Clinical trial publication Serum zinc level in depressed patients during zinc supplementation of imipramine treatment (Journal of affective disorders, 2010) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
N-Acetylcysteine Natural product Systematic review Magnetic resonance spectroscopy biomarkers of anti-inflammatory interve… Systematic review Ketamine and other glutamate receptor modulators for depression in adul… Clinical trial publication N-acetylcysteine as add-on to antidepressant medication in therapy refr…	Amino acid	Phase I	Moderate	20	2 trials 3 Meta-analysis 2 Trial pubs 2 RCT View evidence Registry trials NCT02269540 — A New Treatment Approach for Major Depressive Disorder Based Upon Targeting Monoamine Oxidase A (MAO-A) (COMPLETED) EARLY_PHASE1 NCT02972398 — N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders (UNKNOWN) NA Published literature Systematic review Magnetic resonance spectroscopy biomarkers of anti-inflammatory interventions in mood disorders: A systematic review of clinical trials (Journal of affective disorders, 2025) Systematic review Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder (The Cochrane database of systematic reviews, 2021) Clinical trial publication N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial (BMC psychiatry, 2018) Clinical trial publication The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial (The Journal of clinical psychiatry, 2014) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Omega-3 Fatty Acids Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3…	Nutraceutical	Phase II	Emerging	19	8 trials View evidence Registry trials NCT03732378 — Role of Omega-3 Polyunsaturated Fatty Acid in the Management of Major Depressive Disorder. (COMPLETED) NA NCT00618865 — Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy (COMPLETED) NA NCT05899660 — Impact of Omega 3 in Alcohol Use Disorder (RECRUITING) NA NCT00001146 — Omega-3 Fatty Acids in the Treatment of Bipolar Disorder: A Double-Blind, Placebo-Controlled Trial (COMPLETED) PHASE2 NCT00962598 — The Role Of Omega-3 Fatty Acids In Adolescent Depression (COMPLETED) PHASE2 NCT00963196 — Study of Supplementation of Antidepressants With Fish Oil to Improve Time to Clinical Response (WITHDRAWN) NA NCT05389046 — Study on the Optimal Diagnosis and Treatment Strategy of Major Depressive Disorder Based on Anhedonia (UNKNOWN) NA NCT04158869 — An Investigation of the Relationship Between Omega-3 Fatty Acid Nutrition and Mental Health in Children and Adolescents (COMPLETED) CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	PubChem Examine.com
Vitamin D3 Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results demonstrate that vitamin D has a beneficial impact on bot… Meta Analysis, Review Vitamin C may produce mood-elevating effects in patients with subclinic…	Nutraceutical	Approved	Emerging	19	6 trials 3 Trial pubs 3 RCT View evidence Registry trials NCT04898725 — Effects of Vitamin D Supplementation on Depression and Inflammatory Markers (COMPLETED) NA NCT00005119 — Altered Calcium and Vitamin D in PMDD or Severe PMS (COMPLETED) NA NCT01932931 — Vitamin D, SSRIs and the Musculoskeletal System (COMPLETED) NA NCT03754712 — Effect of Vitamin D Administration Along With SSRIs in Patients With Major Depressive Disorder (UNKNOWN) NA NCT07579078 — Effect of Vitamin D Supplementation on Brain Waves in Female Major Depressive Disorder Patients With Hypovitaminosis D (ENROLLING_BY_INVITATION) NA NCT01390662 — Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression (UNKNOWN) PHASE4 CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	PubChem Examine.com
Magnesium Natural product Meta Analysis Dietary magnesium intake was significantly associated with a reduced ri… Human Study A 6-month follow-up of disability, quality of life, and depressive and… Human Study A combination of probiotics and magnesium orotate attenuate depression.	Nutraceutical	Approved	Emerging	19	8 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT04880460 — Effect of Magnesium Supplementation in Selective Serotonin Reuptake Inhibitors Treated Major Depressive Disorder Patients (COMPLETED) PHASE2 NCT00797966 — Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder (COMPLETED) PHASE2 NCT07198477 — Sleep Disturbances and Their Association With Serum Magnesium Level in Patients With Major Depressive Disorder (NOT_YET_RECRUITING) NCT03877393 — The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (UNKNOWN) NA NCT07458022 — MAGNESIUM & SSRI VS SSRI ALONE AMONG PATIENTS OF MAJOR DEPRESSIVE DISORDER (ACTIVE_NOT_RECRUITING) PHASE2 NCT01941043 — A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment (COMPLETED) PHASE2 NCT07521358 — Magnesium Supplementation With Fluoxetine for Cognitive Function in Depression (COMPLETED) NA NCT00666757 — A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	PubChem Examine.com
Rhodiola Natural product Randomized controlled trial Antidepressants effects of Rhodiola capsule combined with sertraline fo… Randomized controlled trial Rhodiola rosea versus sertraline for major depressive disorder: A rando…	Botanical	Phase III	Moderate	17	2 trials 2 RCT View evidence Registry trials NCT02981225 — Management Strategy for Mild to Moderate Major Depression: Combination of Rhodiola and Saffron Extracts. (COMPLETED) NCT01098318 — Rhodiola Rosea Therapy of Major Depressive Disorder (COMPLETED) PHASE3 Published literature Randomized controlled trial Antidepressants effects of Rhodiola capsule combined with sertraline for major depressive disorder: A randomized double-blind placebo-controlled clinical trial (Journal of affective disorders, 2020) Randomized controlled trial Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2015) CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Curcumin Natural product Meta-analysis Curcumin for depression: a meta-analysis Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive D… Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal a…	Food compound	Approved	Moderate	17	2 trials 2 Meta-analysis 9 Trial pubs 8 RCT View evidence Registry trials NCT01022632 — Effect of Curcumin as Nutraceutical in Patients of Depression (COMPLETED) NA NCT01750359 — Efficacy and Safety Curcumin in Depression (COMPLETED) PHASE4 Published literature Meta-analysis Curcumin for depression: a meta-analysis (Critical reviews in food science and nutrition, 2020) Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials (Phytotherapy research : PTR, 2016) Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication Tetrahydrocurcumin for Major Depressive Disorder with Therapeutic Potential and Mechanistic Insights from Clinical and Preclinical Studies (Molecular neurobiology, 2025) Clinical trial publication Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study (Neurotoxicity research, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) Clinical trial publication Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study (Journal of clinical psychopharmacology, 2015) Clinical trial publication Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2015) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Saffron Natural product Systematic review A systematic review of randomized controlled trials examining the effec… Clinical trial publication Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfun… Clinical trial publication Crocus Sativus L. (saffron) versus sertraline on symptoms of depression…	Botanical	Preclinical	Moderate	17	1 trials 1 Meta-analysis 10 Trial pubs 10 RCT View evidence Registry trials NCT02981225 — Management Strategy for Mild to Moderate Major Depression: Combination of Rhodiola and Saffron Extracts. (COMPLETED) Published literature Systematic review A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes (Journal of integrative medicine, 2015) Clinical trial publication Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfunctions and Depression in Females with Major Depressive Disorder: Findings from a Randomized Clinical Trial (Medicina (Kaunas, Lithuania), 2023) Clinical trial publication Crocus Sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders-a double-blind, randomized intervention study (Psychiatry research, 2019) Clinical trial publication A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression (Journal of clinical pharmacy and therapeutics, 2020) Clinical trial publication Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial (Archives of gynecology and obstetrics, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Coenzyme Q10 Natural product Meta-analysis Reverse cholesterol transport and lipid peroxidation biomarkers in majo… Human Study A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depre…	Nutraceutical	Preclinical	Moderate	17	1 Meta-analysis View evidence Published literature Meta-analysis Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis (Brain, behavior, and immunity, 2023) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
L-Carnitine Natural product Clinical trial publication Acetyl-l-carnitine deficiency in patients with major depressive disorder Clinical trial publication 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression:… Human Study Acetyl-l-carnitine improves depression in senile patients.	Amino acid	Preclinical	Moderate	17	2 Trial pubs View evidence Published literature Clinical trial publication Acetyl-l-carnitine deficiency in patients with major depressive disorder (Proceedings of the National Academy of Sciences of the United States of America, 2018) Clinical trial publication 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results (Bipolar disorders, 2002) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Melatonin Natural product Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists… Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? Cochrane review Psychological therapies for preventing seasonal affective disorder	Nutraceutical	Approved	Moderate	17	8 trials 3 Cochrane 3 Meta-analysis 28 Trial pubs 25 RCT View evidence Registry trials NCT04350567 — Sleep/Wake Cycle and Depression: An Imaging and Treatment Study (COMPLETED) NA NCT03219008 — Multi-Dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics (UNKNOWN) PHASE4 NCT01428661 — Melatonin Agonist Effects of Tasimelteon Versus Placebo in Patients With Major Depressive Disorder (COMPLETED) PHASE2, PHASE3 NCT02940769 — Neurobiological Effects of Light on MDD (TERMINATED) NA NCT04013464 — Effects of Escitalopram on the Sleep EEG Power in Patients With Major Depressive Disorder (COMPLETED) NA NCT05958940 — BioClock: Bright Light Therapy for Depressive Disorders (RECRUITING) NA NCT01357083 — The Study of Serum Melatonin Rhythm Levels in Patients With Major Depressive Disorder (COMPLETED) NCT02750631 — Out-patient Wake Therapy, Light Therapy and Sleep Phase Advance for Depression (COMPLETED) NA Published literature Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies (Neuropsychopharmacology reports, 2025) Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? (Current molecular pharmacology, 2022) Cochrane review Psychological therapies for preventing seasonal affective disorder (The Cochrane database of systematic reviews, 2019) Meta-analysis Efficacy and safety of each class of sleep medication for major depressive disorder with insomnia symptoms: A systematic review and meta-analysis of double-blind randomized controlled trials (Psychiatry and clinical neurosciences, 2025) Meta-analysis Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies (Psychological medicine, 2016) Meta-analysis Comparison of agomelatine and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials (The Australian and New Zealand journal of psychiatry, 2014) Systematic review Evening wear of blue-blocking glasses for sleep and mood disorders: a systematic review (Chronobiology international, 2021) Clinical trial publication Report from a randomized control trial: improved alignment between circadian biology and sleep-wake behavior as a mechanism of depression symptom improvement in evening-type adolescents with depressive symptoms (Journal of child psychology and psychiatry, and allied disciplines, 2023) Clinical trial publication Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double-blind, placebo-controlled trial (Journal of pineal research, 2022) Clinical trial publication Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries (The lancet. Psychiatry, 2022) Clinical trial publication Comparison of the efficacy and safety of melatonin and memantine in the alleviation of cognitive impairments induced by electroconvulsive therapy: A randomized clinical trial (Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020) Clinical trial publication The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial (Journal of psychiatric research, 2019) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Ashwagandha Natural product Human Study A standardized Withania somniferra root extract with piperine alleviate…	Ayurvedic	Preclinical	Moderate	17	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Tryptophan Natural product Meta-analysis Genetic polymorphism involved in major depressive disorder: a systemic… Meta-analysis Metabolomics on depression: A comparison of clinical and animal research Meta-analysis The kynurenine pathway in major depressive disorder under different dis…	Amino acid	Approved	Moderate	17	8 trials 13 Meta-analysis 57 Trial pubs 40 RCT View evidence Registry trials NCT03935685 — Pilot Study of Mirtazapine for the Dual Tx of Depression and CINV in High-Grade Glioma Pts on TMZ (ACTIVE_NOT_RECRUITING) PHASE2 NCT07634458 — Serotonin Variants & Gut Microbiota in Mental Health (NOT_YET_RECRUITING) NCT00033787 — Serotonin Function During Depression (COMPLETED) NCT02356107 — 5-hydroxytryptophan and Creatine for Treatment Resistant Depression Associated With Hypoxia in Females (COMPLETED) PHASE4 NCT02922725 — Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females (TERMINATED) PHASE4 NCT05895747 — 5-HTP and Creatine for Depression R33 Phase (RECRUITING) PHASE2 NCT00097175 — Effects of Tryptophan Depletion on Brain Processing of Emotions in Patients With Mood Disorders (COMPLETED) NCT04395183 — 5-HTP and Creatine for Depression (COMPLETED) PHASE2 Published literature Meta-analysis Genetic polymorphism involved in major depressive disorder: a systemic review and meta-analysis (BMC psychiatry, 2024) Meta-analysis Metabolomics on depression: A comparison of clinical and animal research (Journal of affective disorders, 2024) Meta-analysis The kynurenine pathway in major depressive disorder under different disease states: A systematic review and meta-analysis (Journal of affective disorders, 2023) Meta-analysis The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies (Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 2023) Meta-analysis Linking nervous and immune systems in psychiatric illness: A meta-analysis of the kynurenine pathway (Brain research, 2023) Systematic review The gut microbiota in post-stroke depression: A systematic review of microbial mechanisms and therapeutic targeting of neuroinflammation (Microbiological research, 2026) Clinical trial publication Kynurenine pathway metabolites predict antianhedonic effects of electroconvulsive therapy in patients with treatment-resistant depression (Journal of affective disorders, 2025) Clinical trial publication Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder (Journal of affective disorders, 2025) Clinical trial publication The effect of prebiotic supplementation on serum levels of tryptophan and kynurenine in obese women with major depressive disorder: a double-blinded placebo-controlled randomized clinical trial (BMC research notes, 2024) Clinical trial publication Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial (Brain, behavior, and immunity, 2022) Clinical trial publication Vitamin D moderates the interaction between 5-HTTLPR and childhood abuse in depressive disorders (Scientific reports, 2020) Randomized controlled trial Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study (Psychoneuroendocrinology, 2019) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Chromium Natural product Clinical trial publication Clinical response augments NK cell activity independent of treatment mo…	Nutraceutical	Preclinical	Moderate	17	1 Trial pubs 1 RCT View evidence Published literature Clinical trial publication Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial (Psychological medicine, 2004) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Creatine Natural product	Amino acid	Approved	Moderate	17	8 trials View evidence Registry trials NCT00729755 — Creatine Augmentation Treatment in Major Depressive Disorder Subjects (COMPLETED) NA NCT03138681 — Rapid Antidepressant Effects of ATP and Phosphocreatine (UNKNOWN) PHASE2 NCT02356107 — 5-hydroxytryptophan and Creatine for Treatment Resistant Depression Associated With Hypoxia in Females (COMPLETED) PHASE4 NCT01175616 — Creatine Augmentation in Veterans With SSRI-Resistant Major Depression (WITHDRAWN) PHASE4 NCT03202095 — Creatine for Treatment of Depression Associated With Type 2 Diabetes (WITHDRAWN) PHASE4 NCT01601210 — Dose-Ranging Trial of Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder (COMPLETED) EARLY_PHASE1 NCT04504253 — A Pilot Study of Creatine Monohydrate as an Augmenting Agent for ECT in Persons With Major Depressive Disorder (COMPLETED) PHASE3 NCT02134808 — Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
L-Theanine Natural product	Amino acid	Preclinical	Moderate	17	—	Examine.com	PubChem Examine.com
Creatine Natural product Magnetic resonance spectroscopy biomarkers of anti-inflammatory interve… Effects of SSRI treatment on GABA and glutamate levels in an associativ… Effects of Fish Oil Monotherapy on Depression and Prefrontal Neurochemi…	Amino acid	Approved	Emerging	16	8 trials View evidence Registry trials NCT00729755 — Creatine Augmentation Treatment in Major Depressive Disorder Subjects (COMPLETED) NA NCT03138681 — Rapid Antidepressant Effects of ATP and Phosphocreatine (UNKNOWN) PHASE2 NCT02356107 — 5-hydroxytryptophan and Creatine for Treatment Resistant Depression Associated With Hypoxia in Females (COMPLETED) PHASE4 NCT01175616 — Creatine Augmentation in Veterans With SSRI-Resistant Major Depression (WITHDRAWN) PHASE4 NCT03202095 — Creatine for Treatment of Depression Associated With Type 2 Diabetes (WITHDRAWN) PHASE4 NCT01601210 — Dose-Ranging Trial of Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder (COMPLETED) EARLY_PHASE1 NCT04504253 — A Pilot Study of Creatine Monohydrate as an Augmenting Agent for ECT in Persons With Major Depressive Disorder (COMPLETED) PHASE3 NCT02134808 — Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	PubChem Examine.com
Ginkgo Biloba Natural product Meta Analysis, Review Ginkgo biloba might reduce the risk of depression or depressive symptom… Meta Analysis The results confirm the efficacy of the three herbal active substances…	Botanical	Preclinical	Moderate	12	—	Examine.com, GreenMedInfo	Examine.com GreenMedInfo
Zinc Natural product Cochrane review Oxidative stress and antioxidant parameters in patients with major depr… Meta-analysis Association between serum levels of essential elements (copper, zinc, a… Meta-analysis Zinc supplementation combined with antidepressant drugs for treatment o…	Nutraceutical	Preclinical	Emerging	10	2 trials 1 Cochrane 3 Meta-analysis 9 Trial pubs 6 RCT View evidence Registry trials NCT00693680 — Zinc Supplementation of Imipramine Therapy (COMPLETED) NA NCT04482296 — Effect of Zinc Supplementation on Depression in SSRI-treated Major Depressive Disorder Patients (COMPLETED) NA Published literature Cochrane review Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis (The Journal of clinical psychiatry, 2015) Meta-analysis Association between serum levels of essential elements (copper, zinc, and iron) and major depressive disorder: a systematic review and meta-analysis (Reviews on environmental health, 2026) Meta-analysis Zinc supplementation combined with antidepressant drugs for treatment of patients with depression: a systematic review and meta-analysis (Nutrition reviews, 2021) Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major depressive disorder (European journal of nutrition, 2020) Clinical trial publication Nutraceuticals for major depressive disorder- more is not merrier: An 8-week double-blind, randomised, controlled trial (Journal of affective disorders, 2019) Clinical trial publication Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial (Pharmacological reports : PR, 2015) Clinical trial publication Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression (Nutritional neuroscience, 2014) Clinical trial publication Serum zinc level in depressed patients during zinc supplementation of imipramine treatment (Journal of affective disorders, 2010) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
N-Acetylcysteine Natural product Systematic review Magnetic resonance spectroscopy biomarkers of anti-inflammatory interve… Systematic review Ketamine and other glutamate receptor modulators for depression in adul… Clinical trial publication N-acetylcysteine as add-on to antidepressant medication in therapy refr…	Amino acid	Phase I	Emerging	10	2 trials 3 Meta-analysis 2 Trial pubs 2 RCT View evidence Registry trials NCT02269540 — A New Treatment Approach for Major Depressive Disorder Based Upon Targeting Monoamine Oxidase A (MAO-A) (COMPLETED) EARLY_PHASE1 NCT02972398 — N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders (UNKNOWN) NA Published literature Systematic review Magnetic resonance spectroscopy biomarkers of anti-inflammatory interventions in mood disorders: A systematic review of clinical trials (Journal of affective disorders, 2025) Systematic review Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder (The Cochrane database of systematic reviews, 2021) Clinical trial publication N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial (BMC psychiatry, 2018) Clinical trial publication The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial (The Journal of clinical psychiatry, 2014) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Vitamin B12 Natural product Clinical trial publication Folate metabolism biomarkers from two randomised placebo-controlled cli… Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major dep… Clinical trial publication B vitamins to enhance treatment response to antidepressants in middle-a…	Nutraceutical	Approved	Emerging	10	5 trials 6 Trial pubs 4 RCT View evidence Registry trials NCT00214682 — Beyond Ageing Project: A Study for the Prevention of Depression (COMPLETED) PHASE2 NCT04832178 — Sumor as Adjuvant Therapy in Treatment-resistant Major Depression (UNKNOWN) PHASE4 NCT01369030 — Deplin® P.L.U.S. Program (Progress Through Learning Understanding & Support) (COMPLETED) NCT07200739 — Speech-Based Artificial Intelligence for Detection of Dementia in Danish Patients (DetectAI) (NOT_YET_RECRUITING) NCT00939718 — Comparison of Vitamin B12 Supplementation to Selective Serotonin Reuptake Inhibitor (SSRI) Versus SSRI Antidepressant Treatment Alone (UNKNOWN) NA Published literature Clinical trial publication Folate metabolism biomarkers from two randomised placebo-controlled clinical studies with paroxetine and venlafaxine (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2021) Clinical trial publication EPA and DHA as markers of nutraceutical treatment response in major depressive disorder (European journal of nutrition, 2020) Clinical trial publication B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial (The British journal of psychiatry : the journal of mental science, 2014) Clinical trial publication Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes (Neuroimmunomodulation, 2008) Clinical trial publication The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine (The international journal of neuropsychopharmacology, 2005) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
S-Adenosylmethionine Natural product S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with de… Efficacy of a food supplement based on S-adenosyl methionine and probio… Early score fluctuation and placebo response in a study of major depres…	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
St. John's Wort Natural product	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Folic Acid (Vitamin B9) Natural product Meta Analysis Continuous use of folic acid during pregnancy may reduce the incidence… Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results demonstrate that vitamin D has a beneficial impact on bot…	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Baikal Skullcap Natural product	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
L-Tyrosine Natural product	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Lactobacillus Reuteri Natural product Animal Study, Human Study Assessment of psychotropic-like properties of a probiotic formulation (… Human Study A randomized, double-blinded, placebo-controlled clinical trial on Lact…	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Nefiracetam Natural product	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Red Clover Extract Natural product	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Rose Essential Oil Natural product Human Study 40 arthritic patients divided into 2 groups, one was treated with an es…	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Synbiotics Natural product From gut to glee: Is butyrate a promising antidepressant? A systematic… The Canadian Network for Mood and Anxiety Treatments Task Force Recomme… A systematic review on gut microbiota consortium in the management of d…	Nutraceutical	Preclinical	Moderate	10	—	Examine.com	Examine.com
Vitamin C Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results demonstrate that vitamin D has a beneficial impact on bot… Meta Analysis This meta-analysis suggests that increasing 25(OH)D levels may be a use…	Nutraceutical	Preclinical	Emerging	10	—	GreenMedInfo	PubChem GreenMedInfo
Folate Natural product Meta Analysis Continuous use of folic acid during pregnancy may reduce the incidence… Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3…	Nutraceutical	Preclinical	Emerging	10	—	GreenMedInfo	PubChem GreenMedInfo
Cyclohexane-1,2,3,4,5,6-Hexol Natural product Meta Analysis These results suggest that inositol may be beneficial for depressed pat…	Food compound	Preclinical	Moderate	10	—	Examine.com, GreenMedInfo	PubChem GreenMedInfo Examine.com
Lutein Natural product Meta Analysis High intake of dietary fiber was protectively associated with depressio… Meta Analysis There are high rates of behavioral symptoms in breast cancer survivors,… Human Study A combined high-sugar and high-saturated-fat dietary pattern is associa…	Nutraceutical	Preclinical	Emerging	10	—	GreenMedInfo	PubChem GreenMedInfo
Olive Oil Natural product Human Study A standardized Withania somniferra root extract with piperine alleviate…	Nutraceutical	Preclinical	Emerging	10	—	GreenMedInfo	GreenMedInfo
Saffron Natural product Systematic review A systematic review of randomized controlled trials examining the effec… Clinical trial publication Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfun… Clinical trial publication Crocus Sativus L. (saffron) versus sertraline on symptoms of depression…	Botanical	Preclinical	Emerging	7	1 trials 1 Meta-analysis 10 Trial pubs 10 RCT View evidence Registry trials NCT02981225 — Management Strategy for Mild to Moderate Major Depression: Combination of Rhodiola and Saffron Extracts. (COMPLETED) Published literature Systematic review A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes (Journal of integrative medicine, 2015) Clinical trial publication Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfunctions and Depression in Females with Major Depressive Disorder: Findings from a Randomized Clinical Trial (Medicina (Kaunas, Lithuania), 2023) Clinical trial publication Crocus Sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders-a double-blind, randomized intervention study (Psychiatry research, 2019) Clinical trial publication A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression (Journal of clinical pharmacy and therapeutics, 2020) Clinical trial publication Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial (Archives of gynecology and obstetrics, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Curcumin Natural product Meta-analysis Curcumin for depression: a meta-analysis Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive D… Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal a…	Food compound	Approved	Emerging	7	2 trials 2 Meta-analysis 9 Trial pubs 8 RCT View evidence Registry trials NCT01022632 — Effect of Curcumin as Nutraceutical in Patients of Depression (COMPLETED) NA NCT01750359 — Efficacy and Safety Curcumin in Depression (COMPLETED) PHASE4 Published literature Meta-analysis Curcumin for depression: a meta-analysis (Critical reviews in food science and nutrition, 2020) Meta-analysis The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials (Phytotherapy research : PTR, 2016) Systematic review Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication Tetrahydrocurcumin for Major Depressive Disorder with Therapeutic Potential and Mechanistic Insights from Clinical and Preclinical Studies (Molecular neurobiology, 2025) Clinical trial publication Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study (Neurotoxicity research, 2018) Clinical trial publication Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study (Journal of affective disorders, 2017) Clinical trial publication Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study (Journal of clinical psychopharmacology, 2015) Clinical trial publication Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2015) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Tryptophan Natural product Meta-analysis Genetic polymorphism involved in major depressive disorder: a systemic… Meta-analysis Metabolomics on depression: A comparison of clinical and animal research Meta-analysis The kynurenine pathway in major depressive disorder under different dis…	Amino acid	Approved	Emerging	7	8 trials 13 Meta-analysis 57 Trial pubs 40 RCT View evidence Registry trials NCT03935685 — Pilot Study of Mirtazapine for the Dual Tx of Depression and CINV in High-Grade Glioma Pts on TMZ (ACTIVE_NOT_RECRUITING) PHASE2 NCT07634458 — Serotonin Variants & Gut Microbiota in Mental Health (NOT_YET_RECRUITING) NCT00033787 — Serotonin Function During Depression (COMPLETED) NCT02356107 — 5-hydroxytryptophan and Creatine for Treatment Resistant Depression Associated With Hypoxia in Females (COMPLETED) PHASE4 NCT02922725 — Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females (TERMINATED) PHASE4 NCT05895747 — 5-HTP and Creatine for Depression R33 Phase (RECRUITING) PHASE2 NCT00097175 — Effects of Tryptophan Depletion on Brain Processing of Emotions in Patients With Mood Disorders (COMPLETED) NCT04395183 — 5-HTP and Creatine for Depression (COMPLETED) PHASE2 Published literature Meta-analysis Genetic polymorphism involved in major depressive disorder: a systemic review and meta-analysis (BMC psychiatry, 2024) Meta-analysis Metabolomics on depression: A comparison of clinical and animal research (Journal of affective disorders, 2024) Meta-analysis The kynurenine pathway in major depressive disorder under different disease states: A systematic review and meta-analysis (Journal of affective disorders, 2023) Meta-analysis The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies (Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 2023) Meta-analysis Linking nervous and immune systems in psychiatric illness: A meta-analysis of the kynurenine pathway (Brain research, 2023) Systematic review The gut microbiota in post-stroke depression: A systematic review of microbial mechanisms and therapeutic targeting of neuroinflammation (Microbiological research, 2026) Clinical trial publication Kynurenine pathway metabolites predict antianhedonic effects of electroconvulsive therapy in patients with treatment-resistant depression (Journal of affective disorders, 2025) Clinical trial publication Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder (Journal of affective disorders, 2025) Clinical trial publication The effect of prebiotic supplementation on serum levels of tryptophan and kynurenine in obese women with major depressive disorder: a double-blinded placebo-controlled randomized clinical trial (BMC research notes, 2024) Clinical trial publication Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial (Brain, behavior, and immunity, 2022) Clinical trial publication Vitamin D moderates the interaction between 5-HTTLPR and childhood abuse in depressive disorders (Scientific reports, 2020) Randomized controlled trial Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study (Psychoneuroendocrinology, 2019) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Coenzyme Q10 Natural product Meta-analysis Reverse cholesterol transport and lipid peroxidation biomarkers in majo…	Nutraceutical	Preclinical	Emerging	7	1 Meta-analysis View evidence Published literature Meta-analysis Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis (Brain, behavior, and immunity, 2023) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Chromium Natural product Clinical trial publication Clinical response augments NK cell activity independent of treatment mo…	Nutraceutical	Preclinical	Emerging	7	1 Trial pubs 1 RCT View evidence Published literature Clinical trial publication Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial (Psychological medicine, 2004) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Ashwagandha Natural product Human Study A standardized Withania somniferra root extract with piperine alleviate…	Ayurvedic	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
L-Carnitine Natural product Clinical trial publication Acetyl-l-carnitine deficiency in patients with major depressive disorder Clinical trial publication 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression:… Human Study Acetyl-l-carnitine improves depression in senile patients.	Amino acid	Preclinical	Emerging	7	2 Trial pubs View evidence Published literature Clinical trial publication Acetyl-l-carnitine deficiency in patients with major depressive disorder (Proceedings of the National Academy of Sciences of the United States of America, 2018) Clinical trial publication 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results (Bipolar disorders, 2002) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Melatonin Natural product Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists… Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? Cochrane review Psychological therapies for preventing seasonal affective disorder	Nutraceutical	Approved	Emerging	7	8 trials 3 Cochrane 3 Meta-analysis 28 Trial pubs 25 RCT View evidence Registry trials NCT04350567 — Sleep/Wake Cycle and Depression: An Imaging and Treatment Study (COMPLETED) NA NCT03219008 — Multi-Dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics (UNKNOWN) PHASE4 NCT01428661 — Melatonin Agonist Effects of Tasimelteon Versus Placebo in Patients With Major Depressive Disorder (COMPLETED) PHASE2, PHASE3 NCT02940769 — Neurobiological Effects of Light on MDD (TERMINATED) NA NCT04013464 — Effects of Escitalopram on the Sleep EEG Power in Patients With Major Depressive Disorder (COMPLETED) NA NCT05958940 — BioClock: Bright Light Therapy for Depressive Disorders (RECRUITING) NA NCT01357083 — The Study of Serum Melatonin Rhythm Levels in Patients With Major Depressive Disorder (COMPLETED) NCT02750631 — Out-patient Wake Therapy, Light Therapy and Sleep Phase Advance for Depression (COMPLETED) NA Published literature Cochrane review Augmentation Therapy With Serotonin 5-HT(1A) Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies (Neuropsychopharmacology reports, 2025) Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant? (Current molecular pharmacology, 2022) Cochrane review Psychological therapies for preventing seasonal affective disorder (The Cochrane database of systematic reviews, 2019) Meta-analysis Efficacy and safety of each class of sleep medication for major depressive disorder with insomnia symptoms: A systematic review and meta-analysis of double-blind randomized controlled trials (Psychiatry and clinical neurosciences, 2025) Meta-analysis Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies (Psychological medicine, 2016) Meta-analysis Comparison of agomelatine and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials (The Australian and New Zealand journal of psychiatry, 2014) Systematic review Evening wear of blue-blocking glasses for sleep and mood disorders: a systematic review (Chronobiology international, 2021) Clinical trial publication Report from a randomized control trial: improved alignment between circadian biology and sleep-wake behavior as a mechanism of depression symptom improvement in evening-type adolescents with depressive symptoms (Journal of child psychology and psychiatry, and allied disciplines, 2023) Clinical trial publication Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double-blind, placebo-controlled trial (Journal of pineal research, 2022) Clinical trial publication Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries (The lancet. Psychiatry, 2022) Clinical trial publication Comparison of the efficacy and safety of melatonin and memantine in the alleviation of cognitive impairments induced by electroconvulsive therapy: A randomized clinical trial (Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020) Clinical trial publication The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial (Journal of psychiatric research, 2019) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
L-Theanine Natural product The effects of L-theanine supplementation on the outcomes of patients w… l-theanine adjunct to sertraline for major depressive disorder: A rando…	Amino acid	Preclinical	Emerging	7	—	Examine.com	PubChem Examine.com
Sulforaphane Natural product Nutritional Modulation of Impaired Blood-Brain Barrier Integrity and Fu… Antioxidants in neuropsychiatric disorder prevention: neuroprotection,… Nrf2 regulates the arginase 1(+) microglia phenotype through the initia…	Food compound	Preclinical	Emerging	7	—	ClinicalTrials.gov	PubChem
Ginseng Natural product Medicinal Plants for Major Depressive Disorder Exploring the Therapeutic Potential of Panax Ginseng: A Comprehensive R… The effect of ginseng on sexual function in postmenopausal women with m…	Botanical	Preclinical	Emerging	7	—	ClinicalTrials.gov	—
Chamomile Natural product Understanding the research landscape of over-the-counter herbal product… Putative Antidepressant Effect of Chamomile (Matricaria chamomilla L.)…	Botanical	Preclinical	Emerging	7	—	GreenMedInfo	GreenMedInfo
Niacin Natural product Meta Analysis, Review Current evidence supports adjunctive use of SAMe, methylfolate, omega-3… Meta Analysis These results demonstrate that vitamin D has a beneficial impact on bot… Meta Analysis This meta-analysis suggests that increasing 25(OH)D levels may be a use…	Nutraceutical	Preclinical	Emerging	7	—	GreenMedInfo	PubChem GreenMedInfo
Egcg Natural product Meta Analysis, Review These findings suggest that green tea consumption reduces the risk of d… Meta Analysis, Review These findings suggest that inflammation could be relevant to a large n…	Food compound	Preclinical	Emerging	7	—	GreenMedInfo	PubChem GreenMedInfo
L-Arginine Natural product Effect of l-arginine compared to placebo on sexual function in women wi…	Amino acid	Preclinical	Emerging	7	—	GreenMedInfo	PubChem GreenMedInfo
Kava Natural product Meta Analysis Kava is an effective treatment alternative to pharmaceuticals in non-ps… Human Study A standardized Withania somniferra root extract with piperine alleviate…	Botanical	Preclinical	Emerging	2	—	GreenMedInfo	GreenMedInfo
Tamsulosin Natural product Urinary Incontinence due to Overactive Detrusor Muscle: A Rare Side Eff… Successful treatment of reboxetine-induced urinary hesitancy with tamsu…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Terazosin Natural product Effect of terazosin on sweating in patients with major depressive disor…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Yohimbine Natural product Noradrenergic blockade and memory in patients with major depression and… A systematic review of augmentation strategies for patients with major… Addition of the alpha2-antagonist yohimbine to fluoxetine: effects on r…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Indoramin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Phentolamine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Prazosin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Clonidine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Apraclonidine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Doxazosin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Mianserin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Akuammigine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Rauwolscine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Corynantheine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Oxymetazoline Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Clozapine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Atipamezole Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Vancomycin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Desglymidodrine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Phenylpropanolamine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Dexniguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Niguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Ecopipam Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
4-(2-aminoethyl)pyrocatechol Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.

Disease overview

Remission & chronicity

Alterations

Therapeutics

Natural Products

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