Clomipramine
| Evidence Level: L2 | Predicted Indications: 8 |
Table of Contents
Clomipramine: From Obsessive-Compulsive Disorder to Anxiety Disorder
One-Sentence Summary
Clomipramine is a tricyclic antidepressant with a strong serotonin reuptake effect, originally used to treat obsessive-compulsive disorder (OCD). The TxGNN model predicts it may be effective for anxiety disorder, with 8 registered clinical trials and 20 publications compiled for this prediction. Most of the trials are OCD-focused, so the strongest direct support lies in panic disorder and agoraphobia, which are covered in the literature.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Obsessive-compulsive disorder |
| Predicted New Indication | Anxiety disorder |
| TxGNN Prediction Score | 0.9993 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| 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 pharmacology, clomipramine is a potent serotonin reuptake inhibitor. Its active metabolite, desmethylclomipramine, adds noradrenergic activity.
OCD was historically grouped with anxiety disorders, and serotonergic modulation overlaps with the pathophysiology of panic and other anxiety disorders. Network meta-analyses and the WFSBP guidelines support clomipramine use in panic disorder.
A caveat: the registered trials supplied are mostly OCD-focused (augmentation studies, pediatric SRI partial responders, IV vs oral dosing). Direct randomized evidence in a non-OCD anxiety disorder therefore comes mainly from the published literature rather than the trial registry.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00074815 | Phase 3 | Completed | 124 | CBT added to serotonin reuptake inhibitor treatment in children with OCD who partially responded |
| NCT00004310 | Phase 2 | Unknown | 76 | Intravenous vs oral clomipramine loading in OCD |
| NCT00564564 | Phase 4 | Completed | 21 | Quetiapine vs clomipramine augmentation of SSRIs in SSRI-resistant OCD |
| NCT00466609 | Phase 4 | Completed | 54 | Fluoxetine alone vs fluoxetine plus quetiapine or clomipramine in OCD non-responders |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine augmentation of SSRI/clomipramine in severe OCD |
| NCT01404871 | N/A | Completed | 26 | Predictors of response to clomipramine or escitalopram in OCD |
| NCT05737511 | Phase 4 | Not yet recruiting | 80 | Hydroxyzine vs treatment as usual in panic disorder (clomipramine not the studied drug) |
| NCT02374567 | Phase 3 | Terminated | 407 | Pharmacovigilance in elderly psychiatric inpatients; safety context only |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38014714 | 2023 | Network meta-analysis | Cochrane Database Syst Rev | Pharmacological treatments in panic disorder in adults |
| 35900217 | 2023 | Guideline | World J Biol Psychiatry | WFSBP guidelines for anxiety, OCD and PTSD pharmacotherapy |
| 40788541 | 2026 | Network meta-analysis | Eur Arch Psychiatry Clin Neurosci | Comparative efficacy and acceptability of anxiolytic drugs |
| 40946318 | 2026 | Systematic review | Psychother Psychosom | Treatment options in treatment-resistant anxiety disorders |
| 6373161 | 1984 | RCT | Curr Med Res Opin | Clomipramine vs diazepam in agoraphobia and social phobia in general practice |
| 9585709 | 1998 | Controlled trial | Am J Psychiatry | Aerobic exercise vs clomipramine vs placebo in panic disorder |
| 10665629 | 1999 | Placebo-controlled trial | J Clin Psychiatry | Paroxetine, clomipramine and cognitive therapy in panic disorder |
| 10361962 | 1999 | Randomized trial | Eur Arch Psychiatry Clin Neurosci | Moclobemide vs clomipramine in panic disorder |
| 11277602 | 2001 | Clinical study | J Psychopharmacol | Dose-finding and discontinuation study: 70.3% of 81 panic patients reached full remission |
| 2178909 | 1990 | Review | Drugs | Overview of clomipramine in OCD and panic disorder |
India Market Information
Clomipramine has 20 valid single-ingredient registrations, all oral tablets. The approved indication text is not available in the data compiled for this report. Five examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 34314 | Clonil 10mg Tablet | Tablet (strip of 10) | Not listed |
| 34872 | Clofranil 50mg Tablet | Tablet (strip of 10) | Not listed |
| 6403 | Arimip 75mg Tablet SR | Sustained-release tablet (strip of 10) | Not listed |
| 41714 | Clomip 50mg Tablet | Tablet (strip of 10) | Not listed |
| 78479 | Ecmin 50mg Tablet | Tablet (strip of 10) | Not listed |
Safety Considerations
- Disease-level contraindication signals (knowledge graph, not label text): epilepsy, manic bipolar affective disorder, liver disease, gallbladder disease, substance abuse/dependence, malignant hyperthermia, pheochromocytoma/paraganglioma, glaucoma, hyperthyroidism (Graves disease, thyrotoxicosis), neuroblastoma, and several cancers (duodenum, small intestine, heart, adrenal gland).
- Drug interactions: 318 known interactions in total. 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, clidinium).
- Literature-reported adverse events: pancytopenia (case report), tic induction (tourettism, case report), sexual dysfunction, and anticholinergic effects.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Clomipramine has a long record in panic disorder and agoraphobia, supported by network meta-analyses, guideline documents and several controlled studies, and is widely marketed in India. However, the registered trials are mainly in OCD, and the safety profile is substantial.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Indian regulator
- Mechanism of action data from DrugBank
- Confirmation of the approved indications for the registered products
- Modern randomized trial evidence for the specific anxiety disorder subtype being targeted
- A safety plan covering cardiac, seizure, anticholinergic and serotonergic risks, the high number of interactions, and CYP2D6/CYP2C19 variability
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.