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 an antipsychotic originally used for schizophrenia, bipolar mania and other psychotic disorders. The TxGNN model predicts it may be effective for retinal dystrophy with or without extraocular anomalies, but the only supporting item is 1 publication, a 1967 report of phototoxic adverse reactions, and there are no clinical trials. This prediction should be regarded as a model output without therapeutic evidence.

Quick Overview

Item	Content
Original Indication	Schizophrenia, psychotic disorder, manic bipolar affective disorder (the Canadian licence records contain no indication text)
Predicted New Indication	Retinal dystrophy with or without extraocular anomalies
TxGNN Prediction Score	0.9995
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 3 of 3)
Number of DINs	3 (marketed: 3)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on known information, chlorpromazine is a long-established antipsychotic (a dopamine D2 receptor antagonist), and its efficacy in schizophrenia and other psychotic disorders is well established.

For the predicted indication, a plausible therapeutic link is hard to find. The only publication is a 1967 report of phototoxic reactions to high-dose chlorpromazine and thioridazine. Chlorpromazine is also known to cause ocular effects, including lens and corneal deposits and pigmentary retinopathy at high doses. These are adverse-effect signals, not evidence of benefit. The high TxGNN score most likely reflects network proximity to retinal-related genes or pathways rather than a real therapeutic effect. The safety signal argues against use in retinal disease.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
5336672	1967	Case report/Observational	JAMA	Phototoxic reactions induced by high doses of chlorpromazine and thioridazine (an adverse-effect report, not therapeutic evidence)

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
00232807	TEVA-CHLORPROMAZINE	Not listed	Not listed
00232823	TEVA-CHLORPROMAZINE	Not listed	Not listed
00232831	TEVA-CHLORPROMAZINE	Not listed	Not listed

Safety Considerations

Disease-level cautions (from the knowledge graph, not label text): Chlorpromazine is linked to contraindications in many conditions. The main groups are:
- Cardiovascular: long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, myocardial infarction, orthostatic hypotension, postural orthostatic tachycardia syndrome
- Blood: neutropenia, agranulocytosis, leukopenia, thrombocytopenia, anaemia
- Neurological: epilepsy, basal ganglia disease, multiple system atrophy, focal hand dystonia, blepharospasm
- Other: liver disease, gallbladder disease, hyperglycaemia, benign prostatic hyperplasia, obesity, substance abuse/dependence, female breast carcinoma
Drug Interactions: The interaction screen returned 100 records. The ones listed below are the first 20 shown, and two are rated Major:
- Major: bupropion and morphine
- Moderate (examples): metformin, pioglitazone, epinephrine, hydrocortisone, famotidine, atropine, loperamide, amphotericin B, and several other antidiabetic and anticholinergic drugs
Ocular safety: The available literature points to phototoxicity, and chlorpromazine is known to cause ocular deposits and pigmentary retinopathy at high doses. This is directly relevant to the proposed retinal indication.

Please refer to the package insert for official warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The predicted indication rests on a model score alone. The only publication reports ocular and photosensitivity harm, and there are no registered trials. No therapeutic mechanism for retinal dystrophy is supported, and the safety signal runs in the opposite direction.

To proceed, the following is needed:

Evidence of a plausible mechanism linking chlorpromazine to retinal dystrophy, and the drug’s mechanism of action data
Preclinical (L4) data showing benefit in retinal disease models
Official Canadian package insert warnings and contraindications, together with the approved indication text and dosage forms
An ocular safety assessment, covering retinopathy and phototoxicity

Other predictions in the list: The other eight highest-scoring predictions (for example X-linked and syndromic myopia, hydranencephaly, and congenital glycosylation and metabolic disorders) have no trials or literature and no supported mechanism, so they remain at Hold. The tenth prediction, early-onset schizophrenia, is an extension of an existing indication to a younger population. It is supported only by observational and pharmacogenetic studies (L3), and newer atypical antipsychotics are generally preferred in this group. It is better treated as a research question than as a repurposing candidate.

Disclaimer

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