Clomipramine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Clomipramine: From Obsessive-Compulsive Disorder to Anxiety Disorder
One-Sentence Summary
Clomipramine is a tricyclic antidepressant, originally used to treat obsessive-compulsive disorder (OCD). The TxGNN model predicts it may be effective for anxiety disorder, with 8 clinical trials (mostly in OCD) and 20 publications currently supporting this direction. Direct anxiety-disorder trial evidence is limited, so much of the support is inferred from OCD and panic disorder studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Obsessive-compulsive disorder |
| Predicted New Indication | Anxiety disorder |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L1 (see note under Clinical Trial Evidence) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| 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 metabolite, desmethylclomipramine, adds noradrenergic activity. Together these modulate the limbic and prefrontal circuits involved in anxiety-spectrum conditions.
OCD was historically classified as an anxiety disorder, and the two conditions share symptoms and respond to similar treatments. The literature supports clomipramine's efficacy in panic disorder, including network meta-analyses and treatment guidelines. Several older controlled studies also point to benefit in panic disorder with agoraphobia.
Most of the registered trials are OCD-focused (the original indication), so evidence for pure anxiety disorders is partly inferred from OCD and panic literature.
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 partly responded |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine vs placebo added to SSRI/clomipramine in severe OCD (clomipramine is background therapy) |
| NCT00466609 | Phase 4 | Completed | 54 | Augmentation of fluoxetine with quetiapine or clomipramine in OCD non-responders |
| NCT00564564 | Phase 4 | Completed | 21 | Quetiapine vs clomipramine augmentation of SSRIs in OCD |
| NCT00004310 | Phase 2 | Unknown | 76 | Intravenous vs oral clomipramine pulse loading in OCD |
| NCT01404871 | Not applicable | Completed | 26 | Predictors of response to clomipramine or escitalopram in OCD |
| NCT05737511 | Phase 4 | Not yet recruiting | 80 | Hydroxyzine vs usual treatment in panic disorder (clomipramine is not the tested drug) |
| NCT02374567 | Phase 3 | Terminated | 407 | Pharmacovigilance of psychotropic drugs in elderly psychiatric inpatients |
Note: The L1 level comes from the dataset's scoring. It rests on Phase 3 trials in closely related OCD populations, where clomipramine is mostly background or comparator therapy. None of the trials directly tests clomipramine in a pure anxiety disorder, so the practical strength of evidence for this specific indication is lower than L1 suggests.
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 | Network meta-analysis | Eur Arch Psychiatry Clin Neurosci | Comparative efficacy and acceptability of anxiolytic drugs in anxiety disorders |
| 40946318 | 2026 | Systematic review | Psychother Psychosom | Treatment options for 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 | Clomipramine is effective in OCD but has more adverse events than SSRIs |
| 2178909 | 1990 | Review | Drugs | Overview of clomipramine in OCD and panic disorder |
| 27663940 | 2016 | Meta-analysis | J Am Acad Child Adolesc Psychiatry | Early responses to SSRIs and clomipramine in pediatric OCD |
| 41978943 | 2026 | Meta-analysis | Acta Neuropsychiatr | Parenteral vs oral clomipramine in depression or OCD |
| 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 |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09611P | DEPRANIL TABLET 25 mg | Tablet | Not listed |
| SIN09058P | APO-CLOMIPRAMINE TABLET 10 mg | Film-coated tablet | Not listed |
| SIN09018P | APO-CLOMIPRAMINE TABLET 25 mg | Film-coated tablet | Not listed |
Safety Considerations
- Contraindication signals (from knowledge-graph associations, not label text): epilepsy, manic bipolar disorder, liver disease, gallbladder disease, substance abuse or dependence, malignant hyperthermia, pheochromocytoma and paraganglioma, glaucoma, hyperthyroidism (including Graves disease and thyrotoxicosis), neuroblastoma, and several cancers (duodenum, small intestine, heart, adrenal gland).
- Drug Interactions: 100 interactions were recorded. Major-level examples include epinephrine, bupropion, lorcaserin, potassium citrate and cisapride. Moderate-level examples include famotidine, cimetidine, clarithromycin, morphine, aspirin and several anticholinergic agents (atropine, hyoscyamine, glycopyrronium).
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Clomipramine has long-standing evidence in OCD and panic disorder, supported by network meta-analyses and guidelines, and it is already marketed in Singapore. However, no trial directly tests it in a broad anxiety disorder population, and tolerability issues (anticholinergic effects, cardiac effects, seizure risk) and many drug interactions require careful management.
To proceed, the following is needed:
- Singapore package insert warnings and approved indication text
- Detailed mechanism of action data
- Direct randomised evidence in anxiety disorders (for example panic disorder or agoraphobia)
- A safety monitoring plan covering cardiac risk, seizure history and interacting medicines
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.