Trifluoperazine
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Trifluoperazine: From Antipsychotic Use to Manic Bipolar Affective Disorder
One-Sentence Summary
Trifluoperazine is a typical (first-generation) phenothiazine antipsychotic, primarily used for psychotic disorders. The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 0 clinical trials and 20 publications — mostly mechanistic and case-level evidence — currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Psychotic disorders (antipsychotic use); no India license record found in the evidence pack |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L4 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
The evidence pack’s official DrugBank MOA field is a data gap (DG002), but the repurposing rationale itself identifies trifluoperazine’s pharmacological class: it is a typical phenothiazine antipsychotic whose primary mechanism is D2 dopamine receptor antagonism.
Mania is hypothesized to involve central dopaminergic hyperactivity (the “dopamine hypothesis of mania”). Antimanic efficacy is a long-established, class-level property of typical antipsychotics — this is not a trifluoperazine-specific finding but a pharmacological class effect, which gives the prediction a plausible mechanistic basis (high mechanistic relevance).
That said, the supporting literature in this evidence pack is largely mechanistic or case-report level (e.g., dopaminergic mechanism studies, single case reports of affective disorder) rather than trifluoperazine-specific efficacy trials in mania/bipolar disorder. One historical double-blind study (PMID 14084030) does involve trifluoperazine in mood-related maintenance therapy, but as part of a combination regimen (with tranylcypromine) rather than monotherapy for mania. No completed clinical trials targeting this indication were identified.
Clinical Trial Evidence
Currently no related clinical trials registered
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14084030 | 1963 | Double-blind study | Curr Ther Res Clin Exp | Withdrawal of trifluoperazine in patients maintained on tranylcypromine-trifluoperazine combination therapy — direct trifluoperazine evidence in mood-disorder maintenance |
| 970489 | 1976 | Review/Mechanistic | Am J Psychiatry | Dopamine agonists provoke manic episodes while a dopamine antagonist (pimozide) is antimanic — supports the class-level dopamine-antagonist rationale for mania |
| 14309092 | 1965 | Clinical study | Int J Neuropsychiatry | Evaluates haloperidol (another typical antipsychotic) in management of manic and schizophrenic patients — class-level antimanic precedent |
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews efficacy of typical and atypical antipsychotics for anxiety symptoms comorbid with bipolar disorder |
| 24943390 | 2014 | Cross-sectional cohort | J Clin Psychopharmacol | Prescription patterns of psychotropic medications, including phenothiazines, in bipolar affective disorder patients (Uganda) |
| 13761179 | 1961 | Clinical study | Am J Psychiatry | Combined tranylcypromine-trifluoperazine therapy in agitated depressions — early trifluoperazine-specific affective-disorder study |
| 3935307 | 1985 | Case report | Can J Psychiatry | Bipolar disorder presenting in an adolescent; diagnostic and treatment considerations for affective disorder |
| 2102674 | 1990 | Case report | Br J Psychiatry | Neuroleptic malignant syndrome following trifluoperazine overdose combined with carbamazepine — safety signal |
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotic drugs, including phenothiazines, in pregnant women with psychotic and bipolar mood disorders |
| 40926568 | 2026 | Review | J Appl Toxicol | Phenothiazine derivatives’ use in mania associated with bipolar disorder, and their apoptosis-related pharmacology |
India Market Information
Trifluoperazine is currently not marketed in India according to this evidence pack — no active product license/registration entries were found (0 registrations).
Safety Considerations
- Drug Interactions: DDInter reports 267 total documented interactions for trifluoperazine. Notable Major-severity interactions include Bupropion and Morphine (increased CNS/seizure or respiratory depression risk). Multiple Moderate-severity interactions are also documented with antidiabetic agents (Acarbose, Metformin, Pioglitazone, Alogliptin, Albiglutide, Canagliflozin, Chlorpropamide — relevant given phenothiazines’ known effect on glucose metabolism), anticholinergic agents (Atropine, Hyoscyamine, Glycopyrronium — additive anticholinergic burden), Epinephrine (classic phenothiazine–epinephrine reversal risk), Amphotericin B, and several GI agents (Famotidine, Loperamide, Bisacodyl).
Formal package-insert warnings and contraindications are not available in this evidence pack (data gap DG001, blocking); please refer to the official prescribing information once available.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence level is L4 — supporting literature is mechanistic and case-level rather than trifluoperazine-specific clinical efficacy data for mania, and no clinical trials exist for this indication. A blocking safety data gap (missing official warnings/contraindications, DG001) prevents a proper S1 safety assessment, and the drug is not currently marketed in India.
To proceed, the following is needed:
- Official Indian regulatory package insert (warnings, contraindications) to resolve DG001 (blocking)
- Confirmed DrugBank MOA record to resolve DG002
- Trifluoperazine-specific clinical evidence for mania/bipolar disorder (current literature is class-level, not drug-specific)
- If registration is pursued, confirmation of available dosage forms/routes in the India market
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.