Pimozide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Pimozide: From Tourette Syndrome to Trichotillomania
One-Sentence Summary
Pimozide is a dopamine D2 receptor antagonist antipsychotic, originally used to treat Tourette syndrome. The TxGNN model predicts it may be effective for trichotillomania (compulsive hair pulling), but there are no registered clinical trials and only a small body of older, mostly uncontrolled literature (9 publications, including one small augmentation study from 1992) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tourette syndrome |
| Predicted New Indication | Trichotillomania |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the data compiled for this report. Based on known information, pimozide is a diphenylbutylpiperidine antipsychotic that blocks dopamine D2 receptors. Its efficacy in Tourette syndrome, a condition marked by repetitive, involuntary behaviours, is established.
Trichotillomania, Tourette syndrome and obsessive-compulsive disorder share overlapping features and treatment responses. Dopaminergic dysregulation is implicated in compulsive and repetitive behaviours. A 1992 report (PMID 1532960) described low-dose pimozide added to serotonin reuptake inhibitors (SRIs) in trichotillomania. A later case series with risperidone (a related drug class) in SRI-resistant trichotillomania also reported benefit. This fits the rationale for antipsychotic augmentation in SRI-resistant compulsive disorders.
The evidence is limited to small, older, uncontrolled studies and reviews, so the prediction should be treated as a research question rather than an established treatment option.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36802832 | 2023 | Evidence mapping / review of RCTs | J Cutan Med Surg | Maps randomized evidence on drug treatment of primary psychodermatologic disorders, a group that includes trichotillomania |
| 1532960 | 1992 | Small clinical study | J Clin Psychiatry | Low-dose pimozide added to SRIs in trichotillomania, based on overlap with Tourette syndrome and OCD |
| 10357517 | 1999 | Case series (3 patients) | J Child Adolesc Psychopharmacol | Risperidone added to SRIs gave a robust decrease in symptoms in SRI-refractory trichotillomania; notes earlier benefit with open-label pimozide |
| 15554735 | 2004 | Review | Am J Clin Dermatol | Comprehensive review of pimozide in dermatologic practice, including monosymptomatic hypochondriacal psychosis |
| 30446201 | 2018 | Review | Clin Dermatol | Antipsychotics in dermatology, with central and peripheral effects relevant to skin conditions |
| 27320510 | 2016 | Review | Tijdschr Psychiatr | Treatment options for paediatric trichotillomania |
| 10497682 | 1999 | Review | Ann Acad Med Singap | Overview of trichotillomania as an under-diagnosed psychiatric syndrome |
| 11475941 | 2001 | Review (indirect) | CNS Drugs | Psychogenic excoriation: clinical features and treatment approaches |
| 10900563 | 2000 | Clinical profile (indirect) | Int J Psychiatry Med | Delusional parasitosis, a related psychodermatologic condition |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02245432 | PIMOZIDE | Not specified | Not specified |
| 02245433 | PIMOZIDE | Not specified | Not specified |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): long QT syndrome, familial long QT syndrome, torsades de pointes, sudden cardiac arrest, heart conduction disease, epilepsy, kidney disease, liver disease, gallbladder disease, potassium deficiency, benign prostatic hyperplasia, glaucoma, neuroleptic malignant syndrome, breast carcinoma (female), Alzheimer disease, and neutropenia, agranulocytosis, leukopenia and several congenital neutropenia syndromes.
- Drug Interactions: The interaction screen returned 100 entries. Those with a Major rating include hydrocortisone, amphotericin B (including the lipid complex), bupropion, aprepitant, morphine, lorcaserin, cimetidine, potassium citrate, clarithromycin, picosulfuric acid, and polyethylene glycol with electrolytes. Moderate interactions include famotidine, epinephrine, hyoscyamine, loperamide, atropine, bisacodyl, glycopyrronium, and dicyclomine.
- Combination-specific concern: The literature highlights QT prolongation risk and CYP2D6/CYP3A4 interactions, especially with SSRIs such as fluoxetine and paroxetine. This matters because the proposed use is as an add-on to SRIs. A paroxetine-pimozide interaction case report (PMID 7961347) illustrates this.
Please refer to the Health Canada package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but supporting evidence is limited to small, older, uncontrolled reports and reviews, with no registered clinical trials. Pimozide’s cardiac (QT) risk and interaction profile with SRIs, the very drugs it would be added to, are significant concerns.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada (a blocking gap for safety screening)
- Mechanism of action data
- A controlled study of pimozide augmentation in trichotillomania, with ECG/QT monitoring and CYP2D6/CYP3A4 interaction management
- A comparison against alternatives with better safety profiles, such as other antipsychotics used in SRI-resistant cases
Other TxGNN predictions (for context): Manic bipolar affective disorder (score 0.9999) has the next-strongest literature base, mostly older small studies from 1976–1988, including double-blind comparisons with chlorpromazine, but modern agents have superseded pimozide there. The remaining predictions (insomnia, major affective disorder, ADHD, and rarer conditions) have indirect or no supporting evidence and 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.