Trifluoperazine
| 證據等級: L5 | 預測適應症: 1 個 |
目錄
Trifluoperazine: From Psychotic Disorders to Manic Bipolar Affective Disorder
One-Sentence Summary
Trifluoperazine is a phenothiazine-class antipsychotic classically used for schizophrenia and psychotic disorders. The TxGNN model predicts it may be effective for manic bipolar affective disorder, with no registered clinical trials but 20 supporting publications (largely mechanistic and case-based) currently available.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the current dataset (classically a phenothiazine antipsychotic for schizophrenia/psychotic disorders) |
| Predicted New Indication | Manic Bipolar Affective Disorder |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L4 |
| US Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the evidence pack. Based on general pharmacological knowledge, trifluoperazine is a phenothiazine antipsychotic acting primarily as a dopamine D2 receptor antagonist, with proven efficacy in schizophrenia and other psychotic conditions.
Manic episodes in bipolar disorder are pharmacologically linked to excess dopaminergic activity, and dopamine-blocking agents are an established class for acute mania management. One supporting publication (PMID 970489) directly proposes a dopaminergic mechanism for mania, showing that dopamine-blocking agents (e.g., pimozide) produce an antimanic effect while dopamine-stimulating agents provoke manic episodes — mechanistically consistent with trifluoperazine’s D2 antagonism.
Several older publications also document real-world use of trifluoperazine in combination regimens for bipolar/manic and agitated-depressive patients (e.g., PMID 14084030, 13761179), and a cross-sectional prescribing survey (PMID 24943390) confirms that typical antipsychotics, including phenothiazines, are commonly prescribed for bipolar affective disorder in clinical practice. However, none of this evidence derives from trials specifically designed to test trifluoperazine’s efficacy in bipolar mania — it remains a mechanism- and case-based rationale rather than a confirmed indication.
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 from patients maintained on tranylcypromine + trifluoperazine combination therapy |
| 13761179 | 1961 | Case series | Am J Psychiatry | Combined tranylcypromine-trifluoperazine therapy effective in agitated depression |
| 970489 | 1976 | Mechanism/case study | Am J Psychiatry | Proposes a dopaminergic mechanism in mania; dopamine-blocking drugs show antimanic effect |
| 24943390 | 2014 | Observational (cross-sectional survey) | J Clin Psychopharmacol | Prescribing patterns show typical antipsychotics/phenothiazines commonly used for bipolar affective disorder |
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews antipsychotic efficacy for anxiety symptoms comorbid with bipolar disorder |
| 40926568 | 2026 | Review | J Appl Toxicol | Reviews phenothiazine derivatives’ use in mania/bipolar disorder and psychosis, plus apoptotic effects |
| 6636782 | 1983 | Case series | Wien Klin Wochenschr | MAOI + lithium combination in rapid-cycling bipolar patients resistant to standard neuroleptic/tranquilizer therapy |
| 2102674 | 1990 | Case report | Br J Psychiatry | Neuroleptic malignant syndrome-like presentation after trifluoperazine + carbamazepine overdose |
| 19164500 | 2010 | Case report | J Psychopharmacol | Antipsychotic-induced spontaneous orgasm in a bipolar patient; references historical trifluoperazine association |
| 3935307 | 1985 | Case report | Can J Psychiatry | Case presentation of bipolar disorder in an adolescent |
US Market Information
Trifluoperazine currently has no marketing authorization on record in this dataset — market status is “Not Marketed” with 0 licenses. No product/indication table is available.
Safety Considerations
Please refer to the package insert for safety information. TFDA label warnings, contraindications, and drug-drug interaction data are not currently available in this evidence pack (flagged as a Blocking data gap — DG001).
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence supporting this indication is currently limited to mechanistic rationale and historical case reports/series (Evidence Level L4), with no clinical trials directly testing trifluoperazine in bipolar mania. Additionally, a Blocking safety data gap (missing TFDA warnings/contraindications) prevents completion of the initial safety assessment (S1).
To proceed, the following is needed:
- TFDA (or equivalent regulatory) label data: warnings, contraindications, and drug interaction profile (resolves DG001)
- Confirmed mechanism of action documentation from DrugBank (resolves DG002)
- Prospective or retrospective controlled studies evaluating trifluoperazine specifically in bipolar mania
- Confirmation of original approved indication(s) and marketing status, currently absent from regulatory records
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.