Perphenazine
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
- Perphenazine
- Pharmacist Assessment Report
- Perphenazine: From Schizophrenia to Retinal Dystrophy with or without Extraocular Anomalies
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Perphenazine: From Schizophrenia to Retinal Dystrophy with or without Extraocular Anomalies
One-Sentence Summary
Perphenazine is a phenothiazine antipsychotic originally used for schizophrenia and mixed anxiety and depressive disorder. 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 behind this prediction. That publication is a 1964 case report of drug-induced retinal toxicity from a related drug, so it points to a safety concern rather than a benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia; mixed anxiety and depressive disorder |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 0.9996 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 4 of 4) |
| Number of DINs | 4 (marketed: 4) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on known information, perphenazine is a phenothiazine-class antipsychotic that acts mainly as a dopamine D2 receptor antagonist. Its efficacy in schizophrenia and in mixed anxiety and depression is established. Nothing in the data compiled for this report suggests a mechanism by which it would help an inherited retinal degeneration.
The only supporting item is a 1964 case report describing pigmentary retinopathy in a patient taking very high doses of thioridazine, a different phenothiazine. That is a drug-induced retinal toxicity signal, not a therapeutic one. Phenothiazines as a class carry a known risk of retinal toxicity, so this link raises a safety concern rather than a repurposing rationale.
The high TxGNN score (0.9996) is therefore not backed by any clinical or mechanistic evidence for perphenazine. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. It should be treated as a hypothesis only.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14129300 | 1964 | Case report | The American Journal of Psychiatry | Pigmentary retinopathy associated with thioridazine (not perphenazine) at a maximum daily dose of 1,400 mg. It describes toxicity, not benefit. |
Canada Market Information
| DIN | Product Name | Status |
|---|---|---|
| 00335134 | PERPHENAZINE | Valid (single-ingredient) |
| 00335096 | PERPHENAZINE | Valid (single-ingredient) |
| 00335126 | PERPHENAZINE | Valid (single-ingredient) |
| 00335118 | PERPHENAZINE | Valid (single-ingredient) |
Safety Considerations
- Retinal toxicity (class concern): The only literature item for this prediction documents pigmentary retinopathy with a related phenothiazine. Any ocular use would need careful retinal safety assessment.
- Disease-level contraindication signals (from the knowledge graph, not label text): These include cardiac conditions (long QT syndrome, familial long QT syndrome, torsades de pointes, sudden cardiac arrest, myocardial infarction), orthostatic hypotension, epilepsy, basal ganglia disease, liver disease, blood disorders (neutropenia, agranulocytosis, thrombocytopenia, anemia), hyperglycemia, open-angle glaucoma, benign prostatic hyperplasia and substance abuse/dependence. Other listed conditions are manic bipolar disorder, multiple system atrophy, postural orthostatic tachycardia syndrome, gallbladder disease, obesity, female breast carcinoma, hemoglobinopathy and focal dystonias (including blepharospasm).
- Drug Interactions: 100 interactions were identified. The major-level ones include bupropion, morphine and potassium citrate. Moderate-level ones include antidiabetic agents (metformin, pioglitazone, acarbose, alogliptin, canagliflozin, chlorpropamide, albiglutide), anticholinergics (atropine, hyoscyamine, glycopyrronium), clarithromycin, epinephrine, famotidine, loperamide, lorcaserin and laxatives (bisacodyl, picosulfuric acid).
Conclusion and Next Steps
Decision: Hold
Rationale: The retinal dystrophy prediction rests on a single 1964 case report of toxicity from a different drug. There are no trials and no plausible mechanism. The evidence points toward a safety risk rather than a benefit, so the prediction should not advance on current data.
To proceed, the following is needed:
- Mechanism of action data, to assess any biological link to retinal disease
- Package insert warnings and contraindications from Health Canada
- Any preclinical or clinical evidence specific to perphenazine in retinal dystrophy
- A dedicated retinal safety assessment, given the phenothiazine class signal
- For the anxiety indication: modern controlled data on perphenazine alone, plus a safety plan for elderly patients
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.