Chlorpromazine

Evidence Level: L5

Predicted Indications: 9

Chlorpromazine

Pharmacist Assessment Report

Chlorpromazine: From Schizophrenia and Other Psychotic Disorders to Retinal dystrophy with or without extraocular anomalies

One-Sentence Summary

Chlorpromazine is a long-established antipsychotic, originally used for schizophrenia and related psychotic and manic disorders. The TxGNN model predicts it may be effective for retinal dystrophy with or without extraocular anomalies, but there are 0 clinical trials and only 1 publication (a 1967 case report describing drug-induced phototoxic reactions, which is a safety signal rather than a benefit).

Quick Overview

Item	Content
Original Indication	Schizophrenia and related psychotic disorders (manic bipolar affective disorder, schizoaffective disorder, schizophreniform disorder, and others)
Predicted New Indication	Retinal dystrophy with or without extraocular anomalies
TxGNN Prediction Score	0.9995
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. Chlorpromazine is a phenothiazine antipsychotic, generally understood to act mainly through dopamine D2 receptor antagonism. Its efficacy in psychotic disorders is well established.

The prediction is not well supported. The only supporting record is a 1967 report of phototoxic reactions induced by high doses of chlorpromazine and thioridazine. That report documents drug-induced ocular toxicity, a safety concern, and not a therapeutic effect. No plausible mechanism has been identified by which chlorpromazine would treat inherited retinal degeneration. The high TxGNN score therefore appears to be a model artefact, and the available literature points to potential harm in retinal disease.

Other top-ranked predictions show the same pattern. None of the eight highest-ranked predictions (retinal dystrophy, congenital disorder of glycosylation with defective fucosylation, three myopia entries, hydranencephaly, a polymicrogyria syndrome, Charcot-Marie-Tooth type 1G, atypical glycine encephalopathy) has any clinical trial or literature support, apart from the retinal dystrophy case report above. For the myopia entries, dopamine antagonism would be expected to be unhelpful or counterproductive. The rank-10 prediction, early-onset schizophrenia, is largely an on-label extension and not true repurposing.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
5336672	1967	Case report / toxicology observation	JAMA	Phototoxic reactions induced by high doses of chlorpromazine and thioridazine. This is a safety signal, not evidence of therapeutic benefit. No abstract available.

India Market Information

Approved indication text is not available for these registrations. Main authorizations (5 of 20 shown):

Authorization Number	Product Name	Dosage Form	Approved Indication
Registration No. 35727	Chlorpromazine Hydrochloride Tablet	Strip of 10 tablets	Not specified
Registration No. 186848	Relitil 25mg Tablet	Strip of 10 tablets	Not specified
Registration No. 188795	Relitil 50mg Tablet	Strip of 10 tablets	Not specified
Registration No. 201920	Sun Prazin 100mg Tablet	Strip of 10 tablets	Not specified
Registration No. 221236	Talentil 100mg Tablet	Strip of 10 tablets	Not specified

All 20 registrations are valid oral tablet products, with none cancelled. Several are fixed-dose combination brands with other ingredients (e.g., Chlorectil Plus, Ostil Plus, Normacalm Forte).

Cytotoxicity

Not applicable. Chlorpromazine is not an antineoplastic drug.

Safety Considerations

Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for label-based safety information.

Contraindication signals (from a knowledge graph, not label text): The following disease associations were flagged:
- Cardiac: long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, myocardial infarction and coronary thrombosis.
- Blood: neutropenia, agranulocytosis, leukopenia, thrombocytopenia, anemia (including macrocytic anemia), hemoglobinopathy.
- Neurological: epilepsy, basal ganglia disease, focal hand dystonia, blepharospasm, multiple system atrophy.
- Blood pressure and autonomic: orthostatic hypotension, postural orthostatic tachycardia syndrome.
- Liver and gallbladder: liver disease, gallbladder disease.
- Metabolic: hyperglycemia, obesity disorder, monogenic obesity.
- Other: benign prostatic hyperplasia, substance abuse/dependence, female breast carcinoma.
Drug Interactions: 315 interactions were recorded, and the 20 listed in the data include two Major ones:
- Bupropion
- Morphine
Moderate interactions include:
- Antidiabetic agents (metformin, pioglitazone, alogliptin, canagliflozin, acarbose, albiglutide, chlorpropamide)
- Anticholinergics (atropine, hyoscyamine, glycopyrronium)
- Others (epinephrine, hydrocortisone, famotidine, amphotericin B, loperamide, lorcaserin, bisacodyl)
Ocular signal: The only literature on the predicted indication reports phototoxic and ocular adverse effects at high doses.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction rests on a computational score alone, and the single supporting publication describes drug-induced toxicity and not benefit. There are no clinical trials, no plausible mechanism, and a potential harm signal in the retina.

To proceed, the following is needed:

Package insert warnings and contraindications for the India-marketed products (a blocking gap for safety screening)
Detailed mechanism of action data, and a mechanistic rationale connecting chlorpromazine to retinal dystrophy pathology
Preclinical evidence (e.g., retinal degeneration models) showing benefit and not toxicity
A review of ocular and phototoxicity risk, since retinal toxicity is a known concern
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.