Trifluoperazine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Trifluoperazine: From Schizophrenia 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 no registered clinical trials and only indirect literature (20 publications, mostly reviews, case reports and older descriptive reports) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia, anxiety |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 0.9951 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on general pharmacological knowledge, trifluoperazine is a high-potency phenothiazine antipsychotic whose main action is dopamine D2 receptor antagonism.
Blocking D2 receptors is the shared mechanism behind the efficacy of antipsychotics in acute mania. Schizophrenia and the manic phase of bipolar disorder are both psychotic or mood-disorder conditions treated with this drug class, so the link is biologically plausible. This helps explain the very high TxGNN score.
However, the score comes from a network-based prediction and is not clinical evidence. No trifluoperazine-specific data for mania were found in the compiled material.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
None of the publications below is a randomised trial of trifluoperazine in mania. Most are reviews or case reports on related antipsychotics or on general psychotropic use. The table lists the most relevant items.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews the efficacy of typical and atypical antipsychotics for anxiety symptoms, including those in bipolar disorder |
| 11279762 | 2001 | Review | Cochrane Database Syst Rev | Clotiapine (another neuroleptic) for acute psychotic illness with agitation |
| 40926568 | 2026 | Review | J Appl Toxicol | Phenothiazine derivatives, used in schizophrenia and mania in bipolar disorder, and their effects on apoptosis |
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotic drugs during pregnancy |
| 39202628 | 2024 | Review | Medicina (Kaunas) | Systematic review of oral vertical dyskinesia (“rabbit” syndrome), a drug-induced movement disorder |
| 24943390 | 2014 | Cohort | J Clin Psychopharmacol | Prescription patterns of psychotropic drugs for psychosis in Ugandan hospitals |
| 42813637 | 2026 | Other (genetic analysis) | Curr Drug Targets | Mendelian randomisation study identifying potential therapeutic target genes for bipolar disorder |
| 13761179 | 1961 | Not classified | Am J Psychiatry | Tranylcypromine plus trifluoperazine in agitated depression |
| 14084030 | 1963 | Not classified (double-blind) | Curr Ther Res | Effects of withdrawing trifluoperazine in patients on a tranylcypromine-trifluoperazine combination |
| 14309092 | 1965 | Not classified | Int J Neuropsychiatry | Haloperidol in schizophrenic and manic patients |
India Market Information
Twenty valid registrations are listed in total, all single-ingredient entries. Indication text is not available for these registrations. Many products are fixed-dose combination tablets (e.g. 5 mg/2 mg strengths). The five main entries are shown below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 174136 | Parkin-Plus Tablet | Strip of 10 tablets | Not stated |
| 75901 | Elicalm 5mg Tablet | Strip of 10 tablets | Not stated |
| 153409 | Nucalm Plus 5 mg/2 mg Tablet | Strip of 10 tablets | Not stated |
| 209076 | Sugil 10mg Injection | Vial of 5 ml injection | Not stated |
| 216877 | TC Plus Tablet | Strip of 10 tablets | Not stated |
Safety Considerations
- Contraindications flagged in the knowledge graph (these are drug–disease links from the TxGNN knowledge graph, not label text): multiple system atrophy, postural orthostatic tachycardia syndrome, orthostatic hypotension, hypotensive disorder, epilepsy, liver disease (including cirrhosis, fatty liver and hepatitis), gallbladder disease, blood disorders (thrombocytopenia, neutropenia, agranulocytosis, anaemia, macrocytic anaemia), benign prostatic hyperplasia, female breast carcinoma, glaucoma, vision disorders (including blindness, retinal disease and retinitis), neuroleptic malignant syndrome, Alzheimer disease, and tardive dyskinesia (including lingual-facial-buccal dyskinesia).
- Drug interactions: 267 interactions were identified. Major-level interactions include bupropion and morphine. Moderate-level interactions include:
- Antidiabetic agents: acarbose, alogliptin, albiglutide, canagliflozin, chlorpropamide, metformin, pioglitazone
- Anticholinergic or gastrointestinal agents: atropine, glycopyrronium, hyoscyamine, loperamide, bisacodyl, famotidine
- Others: epinephrine, hydrocortisone, amphotericin B (including the lipid complex), lorcaserin
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is mechanistically plausible, because D2 antagonism underlies antipsychotic efficacy in mania, and the TxGNN score is very high. However, there are no registered clinical trials, no trifluoperazine-specific mania data, and the literature is indirect. Evidence is at L4, and package insert safety data are missing.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Indian-marketed products (currently a blocking gap for safety screening)
- Detailed mechanism of action data (e.g. from DrugBank)
- Trifluoperazine-specific efficacy data in acute mania, such as a systematic search for controlled trials or comparative studies
- Review of the knowledge-graph contraindications and the major interactions (bupropion, morphine) relevant to a bipolar population
- Confirmation of route and formulation fit (oral tablet and injection are available; required routes for the new indication have not yet been assessed)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.