Trifluoperazine
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Trifluoperazine: From Psychotic Disorders to Manic Bipolar Affective Disorder
One-Sentence Summary
Trifluoperazine is a phenothiazine-class antipsychotic historically used for psychotic disorders (schizophrenia). The TxGNN model predicts it may be effective for Manic Bipolar Affective Disorder, with 0 registered clinical trials and 20 supporting publications currently available, though several data gaps remain unresolved.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Psychotic disorders (schizophrenia) — general pharmacological classification; not confirmed by UK licensing data in this Evidence Pack |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L4 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for trifluoperazine is not available in the Evidence Pack (original_moa: [Data Gap]). Based on general pharmacological knowledge, trifluoperazine belongs to the phenothiazine class of typical (first-generation) antipsychotics, and its principal known action is potent antagonism of D2 dopamine receptors — a mechanism shared across the antipsychotic drug class.
The dopaminergic hypothesis of mania (PMID 970489) proposes that dopaminergic overactivity underlies manic episodes, and that D2-receptor blockade produces antimanic effects. This provides a plausible mechanistic bridge between an antipsychotic’s established use in psychotic disorders and its potential utility in bipolar mania — a rationale that is reinforced by the fact that other D2-antagonist antipsychotics (e.g. haloperidol, clotiapine, risperidone) are already used clinically for acute mania, as reflected in the literature evidence below.
However, because the drug-specific MOA data and UK regulatory/safety documentation are both currently gaps (DG001, DG002), the mechanistic argument here rests on class-level pharmacology rather than confirmed trifluoperazine-specific data, which weakens translatability until these gaps are closed.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 970489 | 1976 | Review/Theoretical | Am J Psychiatry | Proposes a dopaminergic mechanism underlying manic episodes; pimozide (D2 antagonist) showed antimanic effect, supporting D2-blockade rationale relevant to trifluoperazine |
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews efficacy of typical and atypical antipsychotics for anxiety symptoms/disorders comorbid with bipolar disorder |
| 14084030 | 1963 | Double-blind study | Curr Ther Res Clin Exp | Double-blind study on withdrawal of trifluoperazine in patients maintained on tranylcypromine + trifluoperazine combination therapy |
| 13761179 | 1961 | Clinical report | Am J Psychiatry | Combined tranylcypromine–trifluoperazine therapy evaluated in patients with agitated depression |
| 24943390 | 2014 | Cohort/Descriptive | J Clin Psychopharmacol | Cross-sectional survey of psychotropic prescribing patterns across schizophrenia, bipolar affective disorder, and unspecified psychosis in Ugandan psychiatric inpatients |
| 40926568 | 2026 | Review | J Appl Toxicol | Reviews phenothiazine derivatives used in mania (bipolar disorder) and psychosis, including apoptotic effects relevant to broader drug repurposing interest |
| 11279762 | 2001 | Cochrane Systematic Review | Cochrane Database Syst Rev | Reviews clotiapine (a related dibenzothiazepine neuroleptic) for acute psychotic illness, supporting class-wide use in acute agitation/psychosis |
| 19461391 | 2009 | Review | J Psychiatr Pract | Reviews use and safety of antipsychotic drugs during pregnancy, including use in bipolar mood episodes |
| 30601177 | 2021 | Review | Am J Ther | Proposes a safety scoring system for psychotropic drug use during lactation, covering bipolar mood episode treatment |
| 39202628 | 2024 | Systematic Review | Medicina (Kaunas) | Systematic review of drug-induced “rabbit syndrome,” a movement disorder associated with typical antipsychotics including trifluoperazine (safety context) |
UK Market Information
No UK marketing authorisation records are currently available in the Evidence Pack. Regulatory status is recorded as Not marketed, with 0 total licenses on file.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: this Evidence Pack flags a Blocking data gap (DG001) — UK/MHRA label warnings and contraindications for trifluoperazine have not yet been retrieved, and drug interaction data returned no results (query_status: not_found). This gap must be resolved before any safety-based go/no-go decision can be made.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Evidence is limited to observational reports, case reports, and reviews (L4) with no completed clinical trials in the manic bipolar affective disorder indication; combined with a Blocking safety data gap (DG001) and the drug’s current “Not marketed” status in the UK, formal safety screening cannot yet proceed.
To proceed, the following is needed:
- Retrieve UK/MHRA (or historical SmPC) warnings, contraindications, and DDI data for trifluoperazine (resolves DG001)
- Confirm drug-specific mechanism of action via DrugBank (resolves DG002)
- Identify any registered or planned clinical trials specifically evaluating trifluoperazine in bipolar mania
- Assess route/formulation availability given the drug is not currently marketed in the UK
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.