Trifluoperazine
| Evidence Level: L5 | Predicted Indications: 10 |
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 there are currently no registered clinical trials and only indirect, class-level literature (none of it a controlled trial of trifluoperazine in mania), so this remains a research question rather than an evidence-backed indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia, anxiety (from the knowledge graph; the Singapore licence record contains no indication text) |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L5 (the scoring in the data compiled for this report lists L4, but no controlled study of trifluoperazine in mania was found, so L5 is the stricter reading under the rules) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this drug. Based on general class knowledge, trifluoperazine is a phenothiazine antipsychotic with potent dopamine D2 receptor antagonism. Its efficacy in schizophrenia is established, and mechanistically it may be applicable to mania.
D2 blockade is the mechanism shared by antipsychotics used for acute mania, so the link is biologically plausible. Schizophrenia and manic episodes of bipolar disorder are both psychotic-spectrum conditions, and several antipsychotics are used in both.
The high TxGNN score is probably driven by trifluoperazine's similarity to other antipsychotics already used in mania, rather than by direct evidence for trifluoperazine itself. The supporting literature is mostly class-level or indirect (antipsychotic safety, adverse effects, prescribing patterns, anxiety efficacy), so it should not be read as proof of efficacy.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
None of the publications below is a controlled trial of trifluoperazine in mania. They are listed in order of relevance, with reviews first.
| 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 (a different neuroleptic) for acute psychotic illness with agitation |
| 40926568 | 2026 | Review | J Appl Toxicol | Phenothiazine derivatives and apoptosis; notes their use in schizophrenia and mania |
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotic drugs during pregnancy |
| 39202628 | 2024 | Review | Medicina (Kaunas) | Systematic review of drug-induced oral vertical dyskinesia ("rabbit" syndrome) |
| 24943390 | 2014 | Cohort | J Clin Psychopharmacol | Prescription patterns of psychotropic drugs for psychosis in Ugandan hospitals |
| 20851282 | 2010 | Case report | Gen Hosp Psychiatry | Risperidone-induced stuttering; mentions trifluoperazine among drugs with similar case reports |
| 19164500 | 2010 | Case report | J Psychopharmacol | Ziprasidone-induced spontaneous orgasm; mentions trifluoperazine among drugs with similar reports |
| 13761179 | 1961 | Not classified | Am J Psychiatry | Combined tranylcypromine-trifluoperazine therapy in agitated depression (older report, no abstract) |
| 14084030 | 1963 | Not classified | Curr Ther Res | Double-blind study of trifluoperazine withdrawal in patients on tranylcypromine plus trifluoperazine (older report, no abstract) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00289P | AA Pharma Trifluoperazine Tablet 5 mg (Apotex Inc) | Tablet, film coated | Not stated in the licence record |
Safety Considerations
- Disease-level contraindications (from the knowledge graph, not label text): the following conditions are linked to trifluoperazine as contraindications:
- Neurological: epilepsy, neuroleptic malignant syndrome, tardive dyskinesia, lingual-facial-buccal dyskinesia, Alzheimer disease, multiple system atrophy
- Cardiovascular and autonomic: orthostatic hypotension, hypotensive disorder, postural orthostatic tachycardia syndrome
- Haematological: neutropenia, agranulocytosis, thrombocytopenia, anaemia (including macrocytic anaemia)
- Hepatic and biliary: liver disease, cirrhosis, fatty liver disease, hepatitis, gallbladder disease
- Eye: glaucoma, vision disorder, blindness, retinal disease, retinitis
- Other: benign prostatic hyperplasia, female breast carcinoma
- Drug Interactions: 100 interactions were identified. Examples:
- Major: bupropion, morphine
- Moderate: antidiabetic agents (acarbose, metformin, pioglitazone, alogliptin, albiglutide, canagliflozin, chlorpropamide), anticholinergics (atropine, hyoscyamine, glycopyrronium), epinephrine, hydrocortisone, amphotericin B, famotidine, loperamide, lorcaserin, bisacodyl
Please refer to the package insert for label warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is biologically plausible because D2 antagonists are used in acute mania, but no trial or direct study supports trifluoperazine in this setting. Established alternatives exist, and the knowledge-graph contraindication profile is extensive (including neutropenia, agranulocytosis, and neuroleptic malignant syndrome). The other nine predicted indications (for example myopia variants, retinal dystrophy and rare congenital disorders) have no supporting evidence and are not recommended for further work.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (HSA)
- Mechanism of action data (DrugBank)
- A targeted literature search for trifluoperazine in mania, including older comparative trials
- A comparison against existing antipsychotics approved for mania, including efficacy and safety
- A safety plan for the contraindicated populations listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.