Thioridazine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Thioridazine: From Schizophrenia to Manic Bipolar Affective Disorder
One-Sentence Summary
Thioridazine is a phenothiazine antipsychotic. The license records in the Evidence Pack contain no indication text, so schizophrenia is taken from general drug knowledge and the retrieved literature. The TxGNN model predicts it may be effective for manic bipolar affective disorder, but there are 0 clinical trials and only a handful of thioridazine-specific publications, mostly old or indirect. The prediction is best regarded as a model hypothesis with very weak clinical support.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia (general knowledge; license records list no indication text) |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (generic ANDA approvals) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. Based on known information, thioridazine is a phenothiazine antipsychotic. Its class mechanism is dopamine D2 and serotonin 5-HT2A receptor antagonism, and the same class mechanism is used in acute mania.
Mania and psychotic disorders share dopaminergic overactivity, so a D2-blocking antipsychotic could plausibly help. A 1980 study reported that pimozide improved manic patients to a degree and over a time course similar to that seen with chlorpromazine and thioridazine. This is supportive but indirect, because thioridazine was a reference drug rather than the test drug.
Caution is needed. The retrieved literature is mostly about other antipsychotics (olanzapine, quetiapine) or is generic, such as pregnancy safety and review articles. No thioridazine-specific mania trial was identified. Thioridazine carries a boxed warning for QTc prolongation, and safer alternatives are available. The TxGNN score is a prediction, not clinical evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17017818 | 2006 | Review | J Clin Psychiatry | Reviews typical and atypical antipsychotics for anxiety symptoms in disorders including bipolar disorder; not thioridazine-specific |
| 11336615 | 2001 | Review | Expert Opin Pharmacother | Olanzapine in non-psychotic disorders; mentions thioridazine only as a historical phenothiazine |
| 19461391 | 2009 | Review | J Psychiatr Pract | Antipsychotic use and safety in pregnancy; general class review |
| 40926568 | 2026 | Review | J Appl Toxicol | Phenothiazine derivatives and apoptosis; notes use in mania of bipolar disorder, focus is cancer-cell biology |
| 6155678 | 1980 | Not classified | Psychopharmacology | Pimozide gave clinical improvement in mania similar in size and time course to chlorpromazine and thioridazine |
| 8448267 | 1993 | Not classified | Biol Psychiatry | Single patient with schizoaffective disorder on thioridazine maintenance; manic episode timing tracked over the year and menstrual cycle |
| 14252012 | 1964 | Not classified | Ann Med Psychol | Thioridazine-barbiturate combined with electroshock for psychomotor excitation and manic reactions (no abstract) |
| 11910256 | 2002 | Clinical pharmacology study | J Clin Psychopharmacol | Quetiapine coadministered with thioridazine in patients including bipolar disorder; pharmacokinetics and safety only |
| 106047 | 1979 | Not classified | J Clin Psychiatry | Four cases of severe neurotoxicity (delirium, seizures, encephalopathy) when lithium was combined with thioridazine |
| 3945208 | 1986 | Not classified | Med J Aust | Encephalopathy with lithium plus thioridazine (no abstract) |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA088004 | Thioridazine Hydrochloride (Mylan Institutional) | Film-coated tablet | Not listed in records |
| ANDA088004 | Thioridazine Hydrochloride (Safecor Health) | Film-coated tablet | Not listed in records |
| ANDA089953 | Thioridazine Hydrochloride (Sun Pharmaceutical) | Film-coated tablet | Not listed in records |
| ANDA088135 | Thioridazine Hydrochloride (Chartwell RX) | Film-coated tablet | Not listed in records |
All listed products are oral. The pack reports 20 licenses in total; only these distinct authorizations are shown.
Safety Considerations
- Key Warnings: The package insert content was not retrieved. The Evidence Pack’s own assessment flags a boxed warning for QTc prolongation, which is a major barrier to any new use.
- Drug Interactions: No interactions were returned from the database query. The literature reports severe neurotoxicity when thioridazine is combined with lithium (PMIDs 106047, 3945208). This matters for mania, where lithium is a standard treatment. It also reports CYP2D6-mediated interference with imipramine metabolism (PMID 8946674). Strict QTc and CYP2D6 safeguards would be required.
Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score is not backed by any thioridazine-specific clinical evidence in mania. The support is class-level or historical, and the QTc boxed warning and the lithium interaction are significant obstacles. Other predicted indications in the pack, such as major affective disorder and ADHD, have slightly more direct thioridazine data, but these are also small, old studies.
To proceed, the following is needed:
- Package insert warnings and contraindications (blocking data gap)
- Detailed mechanism of action data (MOA)
- Controlled, thioridazine-specific efficacy data in mania, compared against current standard agents
- A QTc, lithium co-use and CYP2D6 interaction risk-management plan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.