Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis

Abstract

BackgroundDrug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time.MethodsPubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes.ResultsAmong the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: −3.56 (−6.67, −0.45); 3 months: −3.32 (−3.75, −2.89); 6 months: −7.46 (−12.60, −2.32); 12 months: −5.07 (−6.74, −3.41); 48 months: −8.78 (−13.75, −3.80); 60 months: −11.06 (−16.19, −5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found.ConclusionSelegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson’s Disease: An Updated Review

“…Selegiline was also effective in improving depressive symptoms in PD in a recent meta-analysis [ 52 ]. A systematic review showed that safinamide, a selective reversible MAO-B inhibitor and modulator of voltage-sensitive calcium and sodium channels that also affect glutamatergic neurotransmission, may also be beneficial for depression in PD [ 53 ].…”

Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson’s Disease

“…In this context, selegiline appears to have benefits in improving PD symptoms but has a high risk of adverse events, especially neuropsychiatric issues. Further studies are needed to better understand this correlation and assess the long-term efficacy and safety of selegiline [176].…”

Selegiline modulates inflammatory indicators in RAW 264.7 macrophages and LPS-aggravated CFA-induced rheumatoid arthritis in rats

“…Its primary mechanism of action involves the inhibition of monoamine oxidase (MAO) impeding the process of reuptake of monoamine neurotransmitters inside the central nervous system, leading to an increase in the quantities of physiologically active monoamines present at the synaptic cleft. 18,19 Selegiline is additionally utilized off-label for the manage-ment of attention-deficit hyperactivity disorder. 20 One of the byproducts of the MAO-catalyzed amine oxidation reaction is hydrogen peroxide, which can be further processed into reactive oxygen species to cause cytotoxicity.…”