Clomipramine
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Clomipramine
- Clomipramine: From Depression and Obsessive-Compulsive Disorder to Anxiety Disorder (Panic Disorder and Agoraphobia)
Clomipramine: From Depression and Obsessive-Compulsive Disorder to Anxiety Disorder (Panic Disorder and Agoraphobia)
One-Sentence Summary
Clomipramine is a tricyclic antidepressant known from the supplied literature for treating depression and obsessive-compulsive disorder (OCD). The TxGNN model predicts it may be effective for anxiety disorder, with a score of 99.93%. This prediction is linked to 19 registered clinical trials and 20 publications. Most trials are in OCD, while the strongest support for anxiety comes from older controlled studies in panic disorder and agoraphobia.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied SAHPRA registration data (the approved indication text is blank). The literature describes use in depression and OCD. |
| Predicted New Indication | Anxiety disorder |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L2 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Proceed with Guardrails |
L2 is assigned with a caveat. The only completed Phase 2/3 RCT in the pack (NCT03299166) tests troriluzole, not clomipramine. The clomipramine-specific support is published controlled studies in panic disorder and agoraphobia, with no registered Phase 3 trials.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the supplied record. The following comes from general pharmacology, not from the input. Clomipramine is a potent serotonin reuptake inhibitor. Its active metabolite, desmethylclomipramine, also inhibits norepinephrine reuptake. Serotonergic modulation is the accepted mechanism behind its effect in OCD and in panic and phobic anxiety.
The prediction is reasonable, but “anxiety disorder” is broader than the evidence. Of the 19 trials, most are in OCD, which DSM-5 no longer classes as an anxiety disorder. The evidence therefore supports the panic disorder / agoraphobia and OCD subsets, not anxiety disorders as a whole. Panic disorder with agoraphobia is the closest match to the prediction. A 2023 Cochrane network meta-analysis and several controlled comparisons against imipramine, diazepam, paroxetine and cognitive therapy cover it. Older reviews also describe clomipramine as one of the reference drugs for panic disorder.
Clinical Trial Evidence
No SANCTR or PACTR identifiers were supplied. Only ClinicalTrials.gov records are listed.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00004310 | Phase 2 | Unknown | 76 | IV vs oral pulse-loaded clomipramine, then 12 weeks of maintenance, in OCD. This is the most direct clomipramine trial, but the condition is OCD. |
| NCT00466609 | Phase 4 | Completed | 54 | Double-blind augmentation in OCD patients not responding to first-line drugs: fluoxetine alone vs fluoxetine plus quetiapine vs fluoxetine plus clomipramine. |
| NCT00564564 | Phase 4 | Completed | 21 | Open randomised comparison of quetiapine vs clomipramine added to an SSRI in SSRI-refractory OCD. Small sample. |
| NCT01404871 | N/A | Completed | 26 | OCD patients randomised to clomipramine or escitalopram to identify predictors of medication response. Biomarker-oriented, not an efficacy trial. |
| NCT01148316 | N/A | Completed | 144 | Adaptive treatment strategies for children and adolescents with OCD, mentioning clomipramine and SSRIs as approved options. |
| NCT00074815 | Phase 3 | Completed | 124 | CBT added to serotonin reuptake inhibitor treatment in children with OCD who partially responded. Clomipramine is background therapy at most. |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine vs placebo added to SSRI or clomipramine in severe OCD. Clomipramine is background therapy. |
| NCT03299166 | Phase 2/3 | Completed | 426 | Adjunctive troriluzole vs placebo in OCD with inadequate response to an SSRI or clomipramine. Clomipramine is background therapy, so this gives no direct efficacy evidence for it. |
| NCT02374567 | Phase 3 | Terminated | 407 | Pharmacovigilance of psychopharmacological treatment in older psychiatric inpatients. Not indication-specific. |
| NCT06942494 | N/A | Recruiting | 88 | Family-based CBT self-help for adolescents with OCD who are already on stable medication. Non-pharmacological. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38014714 | 2023 | Network meta-analysis | Cochrane Database Syst Rev | Compares pharmacological treatments for panic disorder in adults. The supplied excerpt does not include the results. |
| 41978943 | 2026 | Systematic review and meta-analysis | Acta Neuropsychiatrica | Asks whether parenteral clomipramine is superior to oral clomipramine or other treatments in depression or OCD. Its scope is depression and OCD, not anxiety. |
| 27663940 | 2016 | Systematic review and meta-analysis | J Am Acad Child Adolesc Psychiatry | Early treatment response to SSRIs and clomipramine in paediatric OCD, including SSRI vs clomipramine efficacy. |
| 8263222 | 1993 | Meta-analysis | J Behav Ther Exp Psychiatry | 25 OCD studies: clomipramine, fluoxetine and exposure therapy were all significantly effective. |
| 10665629 | 1999 | RCT | J Clin Psychiatry | 12-week placebo-controlled comparison of paroxetine, clomipramine and cognitive therapy in panic disorder. The supplied excerpt does not include the results. |
| 1474179 | 1992 | Controlled trial | J Clin Psychopharmacol | Clomipramine, clonazepam and clonidine compared with diphenhydramine as a control in OCD. |
| 3887445 | 1985 | Double-blind trial | Psychiatry Res | 12-week clomipramine vs imipramine trial in OCD (23 patients started). Both showed modest reductions in symptoms. |
| 10221358 | 1999 | Single-blind trial | J Psychopharmacol | 41 panic disorder patients on clomipramine 50–200 mg/day for 14 weeks. 97% were panic-attack-free at the end. |
| 2178909 | 1990 | Review | Drugs | Overview of clomipramine’s pharmacology and its use in OCD and panic disorder. |
| 22204483 | 2012 | Review | Curr Top Med Chem | Treatment strategies for OCD and panic disorder/agoraphobia. |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 35/1.2/0253 | Clomidep | Tablet (oral) | Not available in the supplied data |
Safety Considerations
No warnings, contraindications or drug-interaction records were supplied. The interaction query returned no results. Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
The supplied literature mentions these signals, which are not a substitute for the PI:
- Seizures: a 1991 review cites a 0.4% incidence of seizures.
- Anticholinergic effects: these are described as common with clomipramine.
- Case reports: clomipramine-induced pancytopenia (PMID 3572384) and clomipramine-induced tics in a patient with OCD (PMID 9316681).
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Published controlled studies support clomipramine in panic disorder and agoraphobia, and in OCD. The broad label “anxiety disorder” is not supported, because the registered trials are mainly OCD and none is a clomipramine-specific Phase 3 trial in anxiety. The safety data for South Africa is also missing, which blocks progression to safety screening.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications for Clomidep (Reg. No. 35/1.2/0253), and its currently approved indication.
- Mechanism of action data from DrugBank.
- A narrower target indication (panic disorder with or without agoraphobia) instead of “anxiety disorder”.
- A review of the full text of the panic disorder RCTs and the 2023 Cochrane network meta-analysis for clomipramine-specific efficacy and tolerability.
- A safety monitoring plan covering cardiac conduction, seizure risk, anticholinergic burden, and suicidality in younger patients.
Other predicted indications in the pack are stronger or weaker than this one:
- Agoraphobia, major depressive disorder and endogenous depression reach L2 with the same Proceed with Guardrails recommendation. Depression is closer to confirming an existing use than to repurposing.
- ADHD is a research question only.
- Benign paroxysmal torticollis of infancy and the personality disorders are on Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.