Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations.

Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.

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Déclaration de conflit d'intérêts

Conflict of interest SS has served as a consultant to Acadia, AbbVie/Allergan, Alkermes, Altus, Cerevel, Clearview, Clexio, Done, Enveric Biosciences, Faber Kramer, Gedeon Richter, Genetica, Intra-Cellular Therapies, Janssen, Karuna Therapeutics, Libbs, Lipidio, Longboard, Lundbeck, Merck, Neurocrine Biosciences, Neurawell, Otsuka, Recordati, Relmada Therapeutics, Sage Therapeutics, Saniona, Sunovion, Supernus, Teva, Tonix, and Tris Pharma; he holds options in Genomind, Lipidio, Neurawell and Delix; he has served on speakers bureaus for Abbvie/Allergan, Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva; he has received research and/or grant support from Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn Pharmaceuticals, Daiichi Sankyo- Brazil Eisai, Eli Lilly, Harmony Biosciences, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent. VVdE receives or has received consulting fees from: PsychoTropical Research, NeuraWell Therapeutics, and Aristo Pharma GmbH; he has stock options in NeuraWell Therapeutics. HGR receives or has received: grants from ZonMW (#016.126.059 and #10140021910006), the Hersenstichting (HA2015.01.07), and the Dutch Ministry of Health; and speaking fees from Lundbeck NV and Janssen BV; he is a member of the Scientific Advisory Board of hersenonderzoek.nl; he is a member of the Executive Board of the International Society for Affective Disorders. TKB is a member of the Dutch guideline committee on the use of ECT, and the Dutch guideline committee on pharmacogenetics. KG has equity interests in, and is on the advisory board of NeuraWell Therapeutics. AdB has received research support from Janssen, Lundbeck, and Otsuka and lecture fees for educational meeting from Chiesi, Lundbeck, Roche, Sunovion, Vitria, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda, Chiesi, Recordati, Angelini, Vitria. MF served as a rater for Massachusetts General Hospital Clinical Trials Network and Institute, Boston, MA, USA, and its subsidiaries for the following entities: i) Biohaven Pharmaceuticals, Inc. (“Sponsor”) to provide services for Sponsor trial entitled “A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder,” protocol BHV4157–302; and “A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder,” protocol BHV4157–303 (“Study”), ii) ACADIA Pharmaceuticals Inc. (“Sponsor”) to provide services for Sponsor protocol ACP-103–064 entitled “A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)” (“Study”). MF also received honoraria from the American Society of Clinical Psychopharmacology (ASCP). All other authors declare that they have no conflicts of interest.