Clomipramine
| Evidence Level: L1 | Predicted Indications: 8 |
Table of Contents
Clomipramine: From Obsessive-Compulsive Disorder to Anxiety Disorder
One-Sentence Summary
Clomipramine is a tricyclic serotonin reuptake inhibitor, originally used to treat obsessive-compulsive disorder (OCD). The TxGNN model predicts it may be effective for anxiety disorder, with 8 clinical trials and 20 publications currently linked to this direction. However, the trials mostly concern OCD, not anxiety disorders directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Obsessive-compulsive disorder |
| Predicted New Indication | Anxiety disorder |
| TxGNN Prediction Score | 0.9993 |
| Evidence Level | L1 (formal criteria met, but see the caveat below) |
| Canada Market Status | Marketed (marketed DINs: 5 of 5) |
| Number of DINs | 5 (marketed: 5) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, clomipramine is a potent serotonin reuptake inhibitor, and its metabolite desmethylclomipramine adds noradrenergic activity. This serotonergic and noradrenergic modulation underlies efficacy across anxiety-spectrum conditions.
OCD has long been grouped with anxiety disorders, and the literature describes it as sharing features of both anxiety and affective disorders. Clomipramine’s efficacy in OCD is well established. For panic disorder and agoraphobia, support comes from network meta-analyses, guidelines, and older controlled studies, in which clomipramine served as a reference drug.
Caveat on the evidence level: The Phase 3 trials listed below are mostly OCD augmentation or pediatric OCD studies, and clomipramine is not their test drug. The L1 label reflects the formal rules, but evidence for anxiety disorders themselves is weaker than the label suggests.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00466609 | Phase 4 | Completed | 54 | Augmentation strategies in OCD patients not responding to first-line treatment: fluoxetine alone vs. fluoxetine + quetiapine vs. fluoxetine + clomipramine |
| NCT00564564 | Phase 4 | Completed | 21 | Open-label comparison of quetiapine vs. clomipramine augmentation of SSRIs in OCD |
| NCT00004310 | Phase 2 | Unknown | 76 | Intravenous vs. oral clomipramine in OCD |
| NCT00074815 | Phase 3 | Completed | 124 | Cognitive behavioral therapy added to SRI treatment in pediatric OCD partial responders |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine vs. placebo added to SSRI/clomipramine in severe OCD (pilot) |
| NCT01404871 | Not applicable | Completed | 26 | Predicting medication response in OCD (clomipramine vs. escitalopram) |
| NCT05737511 | Phase 4 | Not yet recruiting | 80 | Hydroxyzine vs. treatment as usual in panic disorder (clomipramine is not the test drug) |
| NCT02374567 | Phase 3 | Terminated | 407 | Pharmacovigilance of psychotropic drugs in elderly inpatients (general safety context only) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38014714 | 2023 | Network meta-analysis | Cochrane Database Syst Rev | Pharmacological treatments for panic disorder in adults |
| 40788541 | 2026 | Systematic review/meta-analysis | Eur Arch Psychiatry Clin Neurosci | Comparative efficacy and acceptability of anxiolytic drugs for anxiety disorders |
| 40946318 | 2026 | Systematic review | Psychother Psychosom | Treatment options in treatment-resistant anxiety disorders |
| 35900217 | 2023 | Guideline | World J Biol Psychiatry | WFSBP guidelines for anxiety, OCD and PTSD (Part II: OCD and PTSD) |
| 18849910 | 2008 | Review | CNS Spectrums | Medical treatment of OCD and anxiety; clomipramine effective but with more adverse events than SSRIs |
| 27663940 | 2016 | Meta-analysis | J Am Acad Child Adolesc Psychiatry | Early treatment responses to SSRIs and clomipramine in pediatric OCD |
| 41978943 | 2026 | Systematic review/meta-analysis | Acta Neuropsychiatrica | Parenteral clomipramine for depression or OCD |
| 2021107 | 1991 | Review | Am Fam Physician | Clomipramine for OCD; notes a 0.4% seizure incidence |
| 11801290 | 2001 | Preclinical/model review | Neurosci Biobehav Rev | Modeling panic attacks; chronic clomipramine effects in an animal model |
| 24214100 | 2013 | Review | Cochrane Database Syst Rev | Pharmacotherapy for trichotillomania |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02497514 | TARO-CLOMIPRAMINE | Not listed | Not listed |
| 02497506 | TARO-CLOMIPRAMINE | Not listed | Not listed |
| 00324019 | ANAFRANIL | Not listed | Not listed |
| 00402591 | ANAFRANIL | Not listed | Not listed |
| 00330566 | ANAFRANIL | Not listed | Not listed |
Safety Considerations
- Contraindications (from the knowledge graph, not label text): epilepsy, manic bipolar affective disorder, liver disease, gallbladder disease, substance abuse/dependence, malignant hyperthermia, phaeochromocytoma and related adrenal or sympathetic tumours, glaucoma, hyperthyroidism (including Graves disease and thyrotoxicosis), neuroblastoma, and several cancers (duodenum, small intestine, heart, adrenal gland).
- Drug Interactions: 100 interactions were identified. Major-level examples include epinephrine, bupropion, lorcaserin, potassium citrate, and cisapride. Moderate-level examples include famotidine, cimetidine, clarithromycin, morphine, acetylsalicylic acid, and several anticholinergics (atropine, hyoscyamine, glycopyrronium).
- Other signals from the literature: seizure risk, anticholinergic and cardiac effects, overdose toxicity typical of tricyclics, and a rare case report of pancytopenia.
Please also refer to the package insert, as label warnings were not available for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Clomipramine is already marketed in Canada, and its serotonergic mechanism is well established in OCD. Support for panic disorder and agoraphobia comes from meta-analyses, guidelines, and small older studies. Registered trials directly testing clomipramine in anxiety disorders are lacking, and the safety burden is substantial, so guardrails are needed.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism of action data
- Controlled trials of clomipramine in a defined anxiety disorder (such as panic disorder), rather than OCD
- A safety plan covering cardiac monitoring (ECG), seizure risk, anticholinergic effects, overdose risk, and the high drug interaction burden
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.