Trifluoperazine
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Trifluoperazine: From Schizophrenia and Anxiety to Manic Bipolar Affective Disorder
One-Sentence Summary
Trifluoperazine is a phenothiazine antipsychotic, originally used to treat schizophrenia and anxiety. The TxGNN model predicts it may be effective for manic bipolar affective disorder, but currently there are 0 registered clinical trials and only a small set of loosely related publications (mostly reviews, case reports, and older studies), so the evidence is mainly computational.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia, anxiety (from knowledge graph indication data; the US license records contain no indication text) |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all licenses cancelled) |
| Number of NDAs | 5 (all ANDAs, all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this drug. Based on its drug class, trifluoperazine is a phenothiazine antipsychotic whose main action is dopamine D2 receptor antagonism. Its efficacy in schizophrenia is established, and mechanistically it may be applicable to manic bipolar affective disorder.
D2 antagonism is a mechanism shared by antipsychotics used to control acute mania and psychotic features in bipolar disorder, so the link is biologically plausible. The high TxGNN score (0.995) is a computational prediction and most likely reflects this class-level similarity. The data compiled for this report contain no drug-specific clinical data for trifluoperazine in mania, so the prediction should be treated as a hypothesis rather than a confirmed finding.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
None of the publications below tests trifluoperazine in mania directly. They provide background on antipsychotics, adverse effects, and older psychiatric use.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews the efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms, including in bipolar disorder |
| 11279762 | 2001 | Review | Cochrane Database Syst Rev | Clotiapine for acute psychotic illness with agitation; background on neuroleptic tranquillisation |
| 39202628 | 2024 | Review | Medicina (Kaunas) | Systematic review of drug-induced “rabbit” syndrome, a movement disorder linked to antipsychotics |
| 40926568 | 2026 | Review | J Appl Toxicol | Phenothiazine derivatives and apoptosis; notes use in schizophrenia and mania in bipolar disorder |
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotics during pregnancy |
| 30601177 | 2021 | Review | Am J Ther | Safety scoring system for psychotropic drugs during lactation |
| 24943390 | 2014 | Cohort | J Clin Psychopharmacol | Cross-sectional survey of psychotropic prescribing for psychosis in Ugandan hospitals |
| 20851282 | 2010 | Case report | Gen Hosp Psychiatry | Risperidone-induced stuttering; mentions trifluoperazine among antipsychotics with similar case reports |
| 19164500 | 2010 | Case report | J Psychopharmacol | Ziprasidone-induced spontaneous orgasm; mentions trifluoperazine among drugs with similar reports |
| 14084030 | 1963 | Double-blind study | Curr Ther Res | Withdrawal of trifluoperazine in patients maintained on tranylcypromine plus trifluoperazine |
US Market Information
All five US licenses are single-ingredient oral tablets and are cancelled. No approved indication text is recorded for them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA085786 | Trifluoperazine Hydrochloride (Sandoz Inc.) | Tablet, film coated | Not recorded |
| ANDA085785 | Trifluoperazine Hydrochloride (Sandoz Inc.) | Tablet, film coated | Not recorded |
| ANDA040209 | Trifluoperazine Hydrochloride (RemedyRepack Inc.) | Tablet, film coated | Not recorded |
| ANDA085789 | Trifluoperazine Hydrochloride (Sandoz Inc.) | Tablet, film coated | Not recorded |
| ANDA085788 | Trifluoperazine Hydrochloride (Sandoz Inc.) | Tablet, film coated | Not recorded |
Safety Considerations
- Disease-level contraindication signals (knowledge graph, not label text):
- Neurological and movement disorders: epilepsy, neuroleptic malignant syndrome, tardive dyskinesia, lingual-facial-buccal dyskinesia, multiple system atrophy, Alzheimer disease
- Blood disorders: agranulocytosis, neutropenia, thrombocytopenia, anemia (including macrocytic anemia)
- Liver and gallbladder disease: liver disease, cirrhosis, fatty liver disease, hepatitis, gallbladder disease
- Cardiovascular and blood pressure: orthostatic hypotension, hypotensive disorder, postural orthostatic tachycardia syndrome
- Eye disorders: glaucoma, vision disorder, blindness, retinal disease, retinitis
- Other: benign prostatic hyperplasia, female breast carcinoma
- Drug Interactions: 100 interactions were identified in total. The main ones listed are:
- Major: bupropion, morphine
- Moderate: anticholinergics (atropine, hyoscyamine, glycopyrronium), antidiabetic drugs (acarbose, metformin, pioglitazone, alogliptin, albiglutide, canagliflozin, chlorpropamide), famotidine, epinephrine, hydrocortisone, amphotericin B, loperamide, lorcaserin, bisacodyl
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is plausible because D2 antagonism is shared with antipsychotics used in mania, but it rests on a model score alone (L4). There are no registered trials and no drug-specific mania data, and all US licenses are cancelled. The knowledge-graph contraindication list is also broad.
To proceed, the following is needed:
- Official package insert warnings and contraindications (FDA)
- Confirmed mechanism of action data (e.g., DrugBank receptor binding profile)
- Drug-specific clinical evidence for trifluoperazine in mania (comparative trials or systematic reviews against established antipsychotics)
- Review of market availability, since there is no active US license
- A safety plan covering hematologic, hepatic, neurological (extrapyramidal and neuroleptic malignant syndrome), and cardiovascular risks
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.