Selegiline
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
- Selegiline
- Pharmacist Assessment Report
- Selegiline: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Selegiline: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
One-Sentence Summary
The TxGNN model predicts it may be useful for schizophrenia (specifically as an add-on for negative symptoms), with 1 clinical trial and 20 publications currently supporting this direction. Note that the highest-scoring prediction (rank 1) has no supporting evidence, so schizophrenia, the best-supported prediction, is the one assessed here.
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 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (research question) |
The rank 1 prediction, perisylvian polymicrogyria with cerebellar hypoplasia and arthrogryposis (score 0.9915), has no trials or literature and no plausible mechanism, so it is not pursued. Ranks 3 to 10 are likewise unsupported (L4 to L5).
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the data compiled for this report. Based on known pharmacology, selegiline is an irreversible, selective MAO-B inhibitor. At higher oral doses (20 mg/day or more) it also inhibits MAO-A. Both actions raise dopamine availability.
Parkinson’s disease is a dopamine-deficiency condition. Negative symptoms of schizophrenia (such as apathy, reduced motivation and blunted affect) are thought to be linked to low dopamine activity in the prefrontal cortex. Selegiline has therefore been tested as an add-on to antipsychotics. Its antioxidant and neuroprotective properties are also discussed in the literature.
There is a theoretical risk that boosting dopamine could worsen positive symptoms such as hallucinations and delusions. The potential for interactions is also high (see Safety Considerations).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00456976 | Early Phase 1 | Completed | 70 | Randomised, placebo-controlled test of selegiline added to antipsychotics for negative symptoms in inpatients with chronic schizophrenia (2007). No results are included in the data compiled, so efficacy cannot be judged. |
No ANZCTR trials were identified in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37087864 | 2023 | Systematic review/Meta-analysis | Eur Neuropsychopharmacol | Appraises oral and transdermal selegiline across psychiatric disorders |
| 26848926 | 2016 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Antioxidant treatments for schizophrenia, with oxidative stress proposed as a mediator of progression |
| 17972359 | 2008 | RCT | Hum Psychopharmacol | 8-week double-blind placebo-controlled study of selegiline added to risperidone for negative symptoms in chronic schizophrenia |
| 15677608 | 2005 | RCT | Am J Psychiatry | Double-blind, placebo-controlled multicentre trial of selegiline augmentation for negative symptoms in outpatients |
| 10587287 | 1999 | RCT | J Clin Psychopharmacol | Double-blind controlled study of deprenyl (selegiline) augmentation in 16 patients with predominantly negative symptoms |
| 8102552 | 1993 | RCT | Biol Psychiatry | Placebo-controlled trial of selegiline 10 mg/day 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 |
| 17405823 | 2007 | Review | Ann Pharmacother | Reviews the role of selegiline in negative symptoms of schizophrenia |
| 16930948 | 2006 | Systematic review | Schizophr Res | Pharmacological treatment of primary negative symptoms |
| 29552749 | 2018 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Miscellaneous treatments for antipsychotic-induced tardive dyskinesia |
The data compiled include no outcome results for these papers, so effect sizes are not reported here.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14430L | Eldepryl | Tablet containing selegiline hydrochloride 5 mg (oral) | Not recorded in the data compiled |
Safety Considerations
Contraindication signals (knowledge graph, not product label text): The drug-disease contraindication links in the knowledge graph include:
- Psychiatric: psychotic disorder, schizophreniform disorder, schizoaffective disorder, bipolar disorder, major affective disorder, and mental disorder in general
- Cardiovascular and autonomic: orthostatic hypotension, postural orthostatic tachycardia syndrome, multiple system atrophy, sudden cardiac arrest, heart conduction disease
- Organ disease: kidney, liver and gallbladder disease
- Tumours: phaeochromocytoma, sympathetic paraganglioma, melanoma, and several cancers
- Movement disorders: tardive dyskinesia and lingual-facial-buccal dyskinesia
The psychotic and schizoaffective disorder signals are directly relevant to the proposed use in schizophrenia and need careful review against the PI.
Drug interactions: 100 interactions were identified. Major-level interactions include:
- Isometheptene
- Bupropion
- Diethylpropion
- Phentermine
- Dexfenfluramine
Moderate-level interactions include:
- Epinephrine
- Metoclopramide
- Insulins and several sulfonylurea or glinide diabetes medicines (chlorpropamide, glimepiride, repaglinide, nateglinide, acetohexamide)
Serotonergic and sympathomimetic agents are often co-prescribed in psychiatry, so interaction risk is significant.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale:
- Schizophrenia is the only prediction with a plausible mechanism and real clinical studies. These are small add-on trials for negative symptoms, and the single registered trial is Early Phase 1, so the evidence supports L3 at most. The other nine predictions have no clinical evidence.
- Because the knowledge graph flags psychotic disorders as a contraindication and the interaction burden is high, the benefit-risk balance is unclear.
To proceed, the following is needed:
- Extraction of outcome data from the existing RCTs (PMIDs 17972359, 15677608, 10587287) and the 2023 meta-analysis, to judge whether negative symptoms improve
- Review of the Australian Product Information for warnings, contraindications and approved indications (including the missing indication text for ARTG 14430L)
- Confirmation of the mechanism of action from DrugBank
- A safety plan for monitoring positive symptoms and managing interactions with co-prescribed psychiatric drugs
- A search of ANZCTR for local trials
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.