Chlorpromazine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Chlorpromazine
- Chlorpromazine: From Schizophrenia and Other Psychotic Disorders to Retinal Dystrophy with or without Extraocular Anomalies
Chlorpromazine: From Schizophrenia and Other Psychotic Disorders to Retinal Dystrophy with or without Extraocular Anomalies
One-Sentence Summary
Chlorpromazine is an antipsychotic originally used for schizophrenia, manic bipolar disorder and other psychotic disorders. The TxGNN model predicts it may be effective for retinal dystrophy with or without extraocular anomalies, but the data compiled for this report show 0 clinical trials and only 1 publication, a 1967 report of phototoxic reactions, which is a safety signal rather than evidence of benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia and other psychotic disorders (manic bipolar affective disorder, schizoaffective disorder, schizophreniform disorder, acute intermittent porphyria, oppositional defiant disorder). Singapore licence entries contain no indication text, so this comes from the knowledge graph. |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Chlorpromazine is a long-established antipsychotic, and its effect in psychotic disorders is generally attributed to dopamine D2 receptor antagonism. No mechanism is identified that would make it useful for inherited retinal dystrophy.
The only retrieved publication (JAMA, 1967) describes phototoxic reactions induced by high doses of chlorpromazine and thioridazine. This points to photosensitivity and potential retinal toxicity, which argues against benefit. The very high TxGNN score most likely reflects a graph-based association with ocular adverse effects rather than a therapeutic effect, and should be treated as a computational signal only.
Other predictions in the list (for example X-linked myopia, syndromic myopia, hydranencephaly and several rare genetic disorders) also have no clinical or literature support. The only one with a plausible clinical context is early-onset schizophrenia. This is an age-defined subgroup of an already approved indication, not a true repurposing target. Observational and genetic-association studies exist for it, but there are no controlled efficacy data in younger patients.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 5336672 | 1967 | Case series / adverse-effect report | JAMA | Phototoxic reactions induced by high doses of chlorpromazine and thioridazine. This is a safety signal, not evidence of benefit. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00095P | LARGO TABLETS 25 mg | Film-coated tablet | Not specified |
| SIN00096P | LARGO TABLET 100 mg | Film-coated tablet | Not specified |
| SIN06832P | CHLORPROMAZINE HYDROCHLORIDE TABLET 50 mg | Film-coated tablet | Not specified |
| SIN07195P | CHLORPROMAZINE 25 TABLET 25 mg | Film-coated tablet | Not specified |
| SIN07528P | CHLORPROMAZINE 100 TABLET 100 mg | Film-coated tablet | Not specified |
All five licences are valid single-ingredient oral products. Beacons Pharmaceuticals holds the two LARGO licences and Remedica holds the other three.
Safety Considerations
- Contraindications / conditions of concern (from knowledge graph, not label text):
- Cardiac and circulatory: long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, myocardial infarction, coronary thrombosis, orthostatic hypotension, postural orthostatic tachycardia syndrome, multiple system atrophy.
- Blood disorders: neutropenia, agranulocytosis, leukopenia, thrombocytopenia, anaemia (including macrocytic), hemoglobinopathy.
- Neurological: epilepsy, basal ganglia disease, focal hand dystonia, blepharospasm.
- Metabolic and other: liver disease, gallbladder disease, hyperglycaemia, obesity (including monogenic), benign prostatic hyperplasia, substance abuse/dependence, female breast carcinoma.
- Drug Interactions: The interaction query returned 100 records. The main ones in the data reviewed:
- Major: bupropion, morphine.
- Moderate: antidiabetic agents (acarbose, metformin, pioglitazone, alogliptin, albiglutide, canagliflozin, chlorpropamide), anticholinergics (atropine, hyoscyamine, glycopyrronium), epinephrine, hydrocortisone, famotidine, amphotericin B, loperamide, lorcaserin, bisacodyl.
- Photosensitivity and ocular toxicity: The only retrieved literature reports phototoxic reactions at high doses.
Please also refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a model score alone. There are no registered trials, and the single publication reports a phototoxicity safety signal that argues against benefit. No mechanism links chlorpromazine to retinal dystrophy. The safety profile, including QT prolongation and blood-disorder concerns, adds further caution.
To proceed, the following is needed:
- Mechanism of action data, to allow a mechanistic-link analysis
- The Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Preclinical evidence of benefit in retinal degeneration models, with the retinal toxicity signal explicitly assessed
- If the team wants a more tractable lead, a separate evaluation of early-onset schizophrenia, framed as an age-specific use of an approved indication, with paediatric safety data
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.