Summary
Clomipramine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. ClinicalTrials.gov lists 5 registered trials linking Clomipramine to Major Depressive Disorder: 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01305707). The largest enrolment is 73336 participants (NCT05952713). Registration activity spans 2005 to 2022. The literature layer holds 15 publications for this pair: 5 Cochrane reviews, 3 meta-analyses, 2 randomised controlled trial publications and 5 clinical trial publications. Publication years run from 2009 to 2025. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Major Depressive Disorder ranks 580 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: 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.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 62.5 (trials 12.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 5 total: 0 recruiting, 0 active / not yet recruiting, 3 completed, 2 other |
| Linked publications | 15 (5 Cochrane reviews, 5 clinical trial publications, 3 meta-analyses, 2 randomised controlled trial publications) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ADRA1A |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00704860 | Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism 2005 | completed | Phase 4 | 27 |
| NCT01305707 | Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression 2009 | terminated | Phase 4 | 104 |
| NCT00944996 | Assessment of Pituitary Adenylate Cyclase Activating Polypeptide-Brain Derived Neurotrophic Factor (PACAP-BDNF) Signaling System Involvement in Etiology and Treatment of Major Depression 2009 | completed | Not applicable | 100 |
| NCT05952713 | Comparative Responses to 15 Different Antidepressants in Major Depressive Disorder 2022 | completed | Not applicable | 73,336 |
| NCT01944657 | Supplemental Transcranial Magnetic Stimulation (TMS) vs. Standard Medication Monotherapy for Treating Major Depression: An Exploratory Field Study 2013 | withdrawn | Not applicable | — |
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-analysisZhou S, Li P, Lyu X et al. · Chinese medical journal · 2025 · PMID 38902199
- Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysisWen S, Yan Y, Shao J et al. · Translational psychiatry · 2025 · PMID 41290573
- Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysisWang Q, Xu Z, Chen X et al. · Andrology · 2025 · PMID 39344496
- Clinical trial publication Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical TrialVos CF, Ter Hark SE, Schellekens AFA et al. · JAMA network open · 2023 · PMID 37155164
- 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 AnalysisJørgensen CK, Juul S, Siddiqui F et al. · Systematic reviews · 2021 · PMID 34389045
- 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 analysesJuul S, Siddiqui F, Barbateskovic M et al. · Systematic reviews · 2021 · PMID 34034811
- Clinical trial publication Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administrationBuoli M, Rovera C, Pozzoli SM et al. · CNS spectrums · 2019 · PMID 29081313
- Cochrane review Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic reviewCao B, Zhu J, Zuckerman H et al. · Progress in neuro-psychopharmacology & biological psychiatry · 2019 · PMID 30611836
- 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-analysisCipriani A, Furukawa TA, Salanti G et al. · Lancet (London, England) · 2018 · PMID 29477251
- Meta-analysis Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysisCipriani A, Zhou X, Del Giovane C et al. · Lancet (London, England) · 2016 · PMID 27289172
- Clinical trial publication Are antidepressants equally effective in the long-term treatment of major depressive disorder?Buoli M, Cumerlato Melter C, Caldiroli A et al. · Human psychopharmacology · 2015 · PMID 25393889
- Clinical trial publication The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramineBech P, Stage KB, Larsen JK et al. · Journal of affective disorders · 2012 · PMID 22381949
- Clinical trial publication Aripiprazole augmentation strategy in clomipramine-resistant depressive patients: an open preliminary studyFabrazzo M, Perris F, Monteleone P et al. · European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2012 · PMID 21784621
- Randomized controlled trial Harm avoidance as a mediator of treatment response to antidepressant treatment of patients with major depressionQuilty LC, Godfrey KM, Kennedy SH et al. · Psychotherapy and psychosomatics · 2010 · PMID 20090398
- Randomized controlled trial Mid-term effects of serial sleep deprivation therapy implemented in cognitive-behavioral treatment on the neuroendocrine response to clomipramine in patients with major depressionKundermann B, Strate P, Hemmeter-Spernal J et al. · Journal of psychiatric research · 2009 · PMID 18930473
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Clomipramine approved for Major Depressive Disorder?
Clomipramine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Clomipramine in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 5 registered trials linking Clomipramine to Major Depressive Disorder: 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01305707). The largest enrolment is 73336 participants (NCT05952713). Registration activity spans 2005 to 2022.
What does the evidence show for Clomipramine in Major Depressive Disorder?
Clomipramine has both completed registered trials and synthesis-level publications linked to Major Depressive Disorder. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.