Clomipramine
| Evidence Level: L1 | Predicted Indications: 8 |
Table of Contents
Clomipramine: Anxiety disorder
One-Sentence Summary
Clomipramine is a tricyclic antidepressant with potent serotonin reuptake inhibition. The TxGNN model predicts it may be useful for anxiety disorder, and the data compiled for this report include 8 clinical trials and 20 publications. Most of this evidence comes from closely related anxiety-spectrum conditions such as panic disorder and compulsive-spectrum disorders, rather than from generalised anxiety trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Anxiety disorder |
| TxGNN Prediction Score | 0.9993 |
| Evidence Level | L1 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Clomipramine is known to be a potent serotonin reuptake inhibitor. Its active metabolite, desmethylclomipramine, adds noradrenergic reuptake inhibition.
Serotonergic and noradrenergic modulation of fear and anxiety circuits (amygdala and prefrontal cortex) is shared across anxiety disorders and closely related conditions. This offers a plausible reason for clomipramine to help in anxiety disorders.
The supporting literature is consistent with this. A Cochrane network meta-analysis in panic disorder (2023) and the WFSBP guidelines support antidepressants, including clomipramine, in anxiety-spectrum disorders. Several randomised and controlled studies also tested clomipramine directly in panic disorder, as listed below.
Clinical Trial Evidence
Most registered trials enrol compulsive-spectrum or other psychiatric populations, so they are indirect evidence for anxiety disorder. None is a dedicated generalised anxiety trial of clomipramine.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00466609 | Phase 4 | Completed | 54 | Double-blind study of fluoxetine alone, fluoxetine plus quetiapine, or fluoxetine plus clomipramine in non-responders to first-line treatment (compulsive-spectrum population) |
| NCT00074815 | Phase 3 | Completed | 124 | Cognitive behavioural therapy added to serotonin reuptake inhibitor treatment in children who were partial responders |
| NCT00004310 | Phase 2 | Unknown | 76 | Randomised comparison of intravenous versus oral pulse-loaded clomipramine, followed by 12 weeks of maintenance |
| NCT00564564 | Phase 4 | Completed | 21 | Open trial comparing quetiapine versus clomipramine augmentation of an SSRI after SSRI failure |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine versus placebo added to SSRI/clomipramine baseline treatment; clomipramine is not the studied intervention |
| NCT01404871 | N/A | Completed | 26 | Randomised to clomipramine or escitalopram to identify predictors of medication response |
| NCT02374567 | Phase 3 | Terminated | 407 | Pharmacovigilance of psychotropic drugs in elderly psychiatric inpatients; not specific to anxiety |
| NCT05737511 | Phase 4 | Not yet recruiting | 80 | Open-label pilot of hydroxyzine versus treatment as usual in panic disorder; clomipramine is not the studied intervention |
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 |
| 40788541 | 2026 | Network meta-analysis | Eur Arch Psychiatry Clin Neurosci | Comparative efficacy and acceptability of anxiolytic drugs across anxiety disorders |
| 40946318 | 2026 | Systematic review | Psychother Psychosom | Reviews drug, psychotherapy and neurostimulation options in treatment-resistant anxiety disorders |
| 35900217 | 2023 | Guideline | World J Biol Psychiatry | WFSBP guideline (version 3) on pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders |
| 22290995 | 1993 | RCT | J Psychopharmacol | Controlled trial of imipramine, clomipramine and an active placebo in panic disorder/agoraphobia (n=54), assessing psychomotor and cognitive effects |
| 10665629 | 1999 | Placebo-controlled trial | J Clin Psychiatry | 12-week placebo-controlled comparison of paroxetine, clomipramine and cognitive therapy in panic disorder |
| 9585709 | 1998 | Controlled trial | Am J Psychiatry | Compares aerobic exercise, clomipramine and placebo in panic disorder |
| 10361962 | 1999 | RCT | Eur Arch Psychiatry Clin Neurosci | Double-blind comparison of moclobemide versus clomipramine 150 mg/day in panic disorder (n=135) |
| 27663940 | 2016 | Meta-analysis | J Am Acad Child Adolesc Psychiatry | Early treatment responses to SSRIs and clomipramine in a paediatric compulsive-spectrum population |
| 41978943 | 2026 | Systematic review and meta-analysis | Acta Neuropsychiatr | Assesses whether parenteral clomipramine is superior to oral clomipramine or other treatments |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1561E | APO-Clomipramine | Tablet containing clomipramine hydrochloride 25 mg | Not recorded in the local data |
Safety Considerations
- Drug interactions: The data compiled for this report list 100 interacting drugs. The following are classified as Major:
- epinephrine
- bupropion
- lorcaserin
- potassium citrate
- cisapride
Moderate interactions include:
- famotidine
- cimetidine
- clarithromycin
- morphine
- acetylsalicylic acid
- chlorpropamide and acetohexamide
- several anticholinergic agents (hyoscyamine, atropine, glycopyrronium, clidinium)
- loperamide
- activated charcoal
- picosulfuric acid
- polyethylene glycol with electrolytes
For warnings and contraindications, please refer to the TGA-approved Product Information (PI) for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The TxGNN score is high (0.9993). Trials and systematic reviews of clomipramine in anxiety-spectrum conditions, including panic disorder, are broadly supportive, so the evidence is rated L1. However, the registered trials are mostly in related populations, and the panic disorder studies are largely older and small. The local licence text does not record an anxiety indication, so any use would be outside the recorded approval.
To proceed, the following is needed:
- Review of the TGA-approved PI for warnings and contraindications, including seizure risk, cardiac effects and anticholinergic effects.
- A medication-interaction check, particularly for the Major interactions listed above.
- Detailed mechanism of action data.
- A clinical protocol that defines the target anxiety disorder subtype, dosing, ECG and adverse-effect monitoring, and exclusion criteria.
- Confirmation against current guidelines that clomipramine is appropriate where first-line agents have failed or are unsuitable.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.