Selegiline

Evidence Level: L5

Predicted Indications: 4

Selegiline

Pharmacist Assessment Report

Selegiline: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

One-Sentence Summary

Selegiline is an irreversible MAO-B inhibitor, originally used to treat Parkinson’s disease and also associated with depressive disorders. The TxGNN model predicts it may be effective for schizophrenia (specifically as an add-on for negative symptoms), with 1 clinical trial and 20 publications currently supporting this direction. The evidence is still at the research-question stage and not yet strong enough to support a clinical decision.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
TxGNN Prediction Score	0.9915
Evidence Level	L5 (schizophrenia); L5 for the rank 1 prediction
India Market Status	Listed in a compiled Indian medicine price dataset (8 of 8) – CDSCO approval status is not included in this data
Number of Listed Products	8 (valid: 8)
Recommended Decision	Hold (rank 1 prediction); schizophrenia is a research question

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, selegiline is an irreversible, selective MAO-B inhibitor. At higher oral doses (≥20 mg/day) it also loses selectivity and inhibits MAO-A. Its efficacy in Parkinson’s disease is established, and it has dopaminergic and possibly antioxidant effects.

The rationale for schizophrenia centres on negative and cognitive symptoms, which are linked to low dopamine activity in the prefrontal cortex. Blocking dopamine breakdown could plausibly help as an add-on to antipsychotics, which treat positive symptoms well but have limited effect on negative ones. The antioxidant and neuroprotective angle is biologically plausible but less established.

The other predictions are much weaker. For the rank 1 prediction (a rare genetic cortical malformation syndrome) and rank 3 (a congenital disorder of glycosylation), no mechanistic link to MAO-B inhibition was found, and they are likely TxGNN model (deep learning) artifacts. For rank 4 (retinal dystrophy), only a general neuroprotection rationale exists, supported by one indirect review.

Clinical Trial Evidence

Schizophrenia (rank 2):

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00456976	Early Phase 1	Completed	70	Randomized trial of selegiline vs placebo added to antipsychotics for negative symptoms in inpatients with chronic schizophrenia (2007). No results are available in the compiled data, so efficacy cannot be judged.

No clinical trials are registered for the other three predicted indications (rank 1, 3 and 4).

Literature Evidence

Schizophrenia (selected from 20 publications, prioritising randomized trials and reviews directly about selegiline):

PMID	Year	Type	Journal	Key Findings
15677608	2005	RCT (double-blind, multicenter)	Am J Psychiatry	Selegiline augmentation of antipsychotics for negative symptoms in outpatients with moderate or greater severity
17972359	2008	RCT (double-blind)	Hum Psychopharmacol	8-week selegiline add-on to risperidone for negative symptoms in chronic schizophrenia; notes earlier results were contradictory
10587287	1999	RCT (double-blind, small)	J Clin Psychopharmacol	Deprenyl (selegiline) augmentation for negative symptoms; 16 clinically stable patients
8102552	1993	RCT (placebo-controlled)	Biol Psychiatry	Selegiline 10 mg/day vs placebo for 6 weeks in 33 patients with tardive dyskinesia
8627275	1996	Open-label pilot	J Nerv Ment Dis	Low-dose selegiline (5 mg twice daily) added to antipsychotics in 21 patients with chronic schizophrenia or schizoaffective disorder, testing a dopamine-deficiency hypothesis
37087864	2023	Systematic review and meta-analysis	Eur Neuropsychopharmacol	Efficacy and safety of oral and transdermal selegiline across psychiatric disorders
17405823	2007	Review	Ann Pharmacother	Role of selegiline in treating negative symptoms of schizophrenia
16930948	2006	Systematic review	Schizophr Res	Pharmacological treatments for primary negative symptoms
26848926	2016	Systematic review (Cochrane)	Cochrane Database Syst Rev	Antioxidant treatments for schizophrenia
29552749	2018	Systematic review (Cochrane)	Cochrane Database Syst Rev	Miscellaneous treatments for antipsychotic-induced tardive dyskinesia

For retinal dystrophy (rank 4), only one indirect review is available: 16392036 (2005, Cell Mol Neurobiol), on protein aggregation in retinal cells and cell-protection approaches. It does not show that selegiline treats retinal dystrophy. No literature is available for rank 1 or rank 3.

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
205731	Selgelin 5mg Tablet (D D Pharmaceuticals)	Strip of 10 tablets	Not specified
203238	Selerin 5mg Tablet (Cipla Ltd)	Strip of 10 tablets	Not specified
77756	Eldepryl 10mg Tablet (Themis Medicare Ltd)	Strip of 10 tablets	Not specified
201769	Selgin 10mg Tablet (Intas Pharmaceuticals Ltd)	Strip of 10 tablets	Not specified
114426	Jumax 5mg Tablet (Torrent Pharmaceuticals Ltd)	Strip of 10 tablets	Not specified

There are 8 valid single-ingredient registrations in total, all oral tablets, with none cancelled.

Safety Considerations

Contraindications suggested by the knowledge graph (these are graph associations, not label text): multiple system atrophy, orthostatic hypotension, postural orthostatic tachycardia syndrome, kidney disease, liver disease, gallbladder disease, bipolar disorder, major affective disorder, psychotic disorders (including schizophreniform and schizoaffective disorder), mental disorder, melanoma, sudden cardiac arrest, heart conduction disease, phaeochromocytoma and related adrenal or sympathetic tumours, certain small intestine, duodenum and heart cancers, and tardive dyskinesia. Several psychiatric entries in this list overlap with the proposed schizophrenia use and should be examined carefully.
Drug Interactions: 123 interactions were identified in total. Major interactions in the data reviewed include isometheptene, bupropion, diethylpropion, phentermine and dexfenfluramine. Moderate interactions include epinephrine, metoclopramide, and several antidiabetic agents (sulfonylureas, repaglinide, nateglinide and multiple insulins), which carry a risk of low blood sugar.

Please refer to the package insert for the full warnings, as label warnings and contraindications are not available in the data compiled for this report.

Conclusion and Next Steps

Decision: Hold (for the rank 1 prediction and the other low-evidence predictions). Schizophrenia add-on therapy is best treated as a research question, not a candidate ready to move forward.

Rationale:

The top-ranked prediction has no trials, no literature and no mechanistic link, so a high TxGNN score alone is not sufficient.
Schizophrenia has a plausible dopaminergic mechanism and several small randomized studies of selegiline add-on for negative symptoms. However, the only registered trial is Early Phase 1 with no results available, earlier findings were described as contradictory, and the knowledge graph flags psychotic disorders as a contraindication area.

To proceed, the following is needed:

Package insert warnings and contraindications from the India registrations (currently a blocking data gap)
Detailed mechanism of action data
Extraction and appraisal of the outcomes of the randomized schizophrenia studies, together with the 2023 meta-analysis
A dedicated safety assessment for patients with psychotic disorders, including interaction management with antipsychotics and antidepressants
Confirmation of the approved indications on the India registrations
Disclaimer

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