Imagine you’re trying out different recipes for chocolate chip cookies, and you want to know how the baking time affects the taste. Well, a group of scientists conducted a study to analyze how the effectiveness and safety of a drug called selegiline change over time for people with Parkinson’s disease. They gathered information from various sources to see if this drug could improve symptoms like tremors and depression. The results showed that as treatment duration increased, selegiline was more effective in reducing overall symptoms. However, it also carried a higher risk of causing adverse events, particularly in the area of mental health. While the findings were generally consistent, there were some variations in outcomes reported by different studies. The research didn’t find any significant differences in adverse events when comparing selegiline with other active treatments. Overall, this systematic review sheds light on the potential benefits and risks of using selegiline for Parkinson’s disease, but it’s always important to consult with a healthcare professional before making any treatment decisions.

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.

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