Chlorpromazine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Chlorpromazine
- Chlorpromazine: From Schizophrenia and Other Psychotic Disorders to Retinal Dystrophy
Chlorpromazine: From Schizophrenia and Other Psychotic Disorders to Retinal Dystrophy
One-Sentence Summary
Chlorpromazine is an antipsychotic originally used for schizophrenia, bipolar mania and related psychotic disorders. The TxGNN model ranks retinal dystrophy with or without extraocular anomalies as its top predicted new use, but there are 0 clinical trials and only 1 publication (a 1967 report of drug-induced phototoxic reactions), which points to harm rather than benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia, bipolar mania, psychotic disorders (the New Zealand licence records contain no indication text; these indications come from the knowledge graph) |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licence) |
| Number of Authorizations | 3 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From pharmacology data, chlorpromazine acts on many receptors: dopamine D1–D5, serotonin (5-HT1A, 2A, 2C, 6, 7), alpha-2 adrenoceptors and histamine H1. Its antipsychotic effect is generally attributed to dopamine D2 antagonism.
For the top prediction, retinal dystrophy, no plausible therapeutic link is supported. The only supporting item is a 1967 report of phototoxic reactions from high-dose chlorpromazine and thioridazine. Phenothiazines accumulate in melanin-containing tissues such as the retina and uvea, which suggests a safety liability rather than a treatment rationale. The very high model score is not backed by any clinical evidence.
Other predictions fare no better:
- Early-onset schizophrenia (score 99.47%) is the most coherent. It extends the existing schizophrenia indication to a younger age group. The six supporting papers are indirect (genetic association, neuroimaging, comorbidity and dosing studies), with no RCT of chlorpromazine in this population. Its status is a research question.
- Myopia entries (X-linked, syndromic, female-limited): dopamine antagonism may not help and could be unfavourable.
- Congenital glycosylation disorder, hydranencephaly, polymicrogyria, Charcot-Marie-Tooth 1G, atypical glycine encephalopathy: no evidence and no supported mechanism. Chlorpromazine lowers the seizure threshold, a concern in neurometabolic disease.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 5336672 | 1967 | Case report / toxicity observation | JAMA | Phototoxic reactions induced by high doses of chlorpromazine and thioridazine; this documents harm, not therapeutic benefit |
For the best-supported alternative, early-onset schizophrenia, the supplied papers are indirect: 28976410 (comorbid OCD, 2017), 24854724 (neurological soft signs, 2015), 10703271 (age at onset and neuroleptic dose, 1999), 22802957 (MRI grey matter, 2012), 18408624 (BDNF and chlorpromazine-induced extrapyramidal syndrome, 2008) and 17915974 (AKT1 polymorphisms and antipsychotic response, 2007).
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 202592 | Largactil | Tab 100 mg | Not recorded (cancelled) |
| 202576 | Largactil | Tab 25 mg | Not recorded (cancelled) |
| 202525 | Largactil | Inj 25 mg per ml, 2 ml | Not recorded (cancelled) |
Safety Considerations
The package insert warnings and contraindications were not available in the data compiled for this report, so please refer to the package insert for label safety information.
- Knowledge-graph contraindication signals (not label text) include:
- Cardiovascular: long QT syndrome, torsades de pointes, orthostatic hypotension, sudden cardiac arrest, heart conduction disease, myocardial infarction.
- Haematological: neutropenia, agranulocytosis, leukopenia, thrombocytopenia, anaemia.
- Neurological: epilepsy, basal ganglia disease, dystonia, blepharospasm, multiple system atrophy.
- Other: liver disease, gallbladder disease, hyperglycaemia, obesity, benign prostatic hyperplasia, breast carcinoma, substance abuse/dependence.
- Ocular and phototoxicity concern: the only evidence for the top predicted indication describes phototoxic reactions, and phenothiazines accumulate in melanin-containing ocular tissue.
- Receptor pharmacology: the interaction data compiled lists 16 receptor and channel targets (serotonin, dopamine, alpha-2 adrenergic, histamine H1, TRPC5, Maxi Cl⁻). It contains no drug-drug interaction entries with graded severity.
- Early-onset schizophrenia: paediatric and adolescent safety (extrapyramidal symptoms, sedation, metabolic effects) would need evaluation against modern alternatives.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction, retinal dystrophy, has no clinical trials, and its single publication reports toxicity rather than benefit. All three New Zealand licences are cancelled, and label safety data is missing. Only early-onset schizophrenia is a coherent research question, as an age-subgroup extension of an existing use.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (a blocking data gap for safety screening)
- Mechanism of action data (for example from DrugBank)
- For early-onset schizophrenia: controlled paediatric/adolescent efficacy and safety data compared with current alternatives
- For retinal dystrophy: ocular toxicity assessment before any further consideration
- Confirmation of whether any chlorpromazine product is currently available in New Zealand
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.