Comparative efficacy and acceptability of drug treatments for Parkinson’s disease with depression: A systematic review with network meta-analysis

Depressive symptom is the prevailing non-motor symptom of Parkinson's disease (PD). Drug treatments for depressed PD (dPD) can mitigate the symptoms of patients. However, the results are discordant and need further analysis. This systematic review with network meta-analysis aims to evaluate the drug treatments for dPD. We included double-blind, randomized controlled trials to compare antidepressants with placebo or other antidepressants in dPD. We performed traditional pairwise analysis and network meta-analysis concerning the efficacy, acceptability, depression score, and adverse effect. The surface under the cumulative ranking curve was to assess the ranking probabilities of the enrolled agents. We enrolled 62 studies, including 12,353 subjects, to analyze these estimates. For the traditional pairwise meta-analysis, dopamine agonist (DOP; OR = 2.20 [95% CI, 1.46 to 3.33]) and selective serotonin reuptake inhibitor (SSRI; OR = 2.30 [95% CI, 1.15 to 4.60]) were observed to improve the efficacy compared with placebo. For network meta-analysis, DOP was observed to improve the efficacy compared with placebo (OR = -0.84 [95% CI, -1.20 to -0.48]). Both direct and indirect evidence showed that several treatments, e.g., DOP, monoamine-oxidase inhibitor, serotonin-norepinephrine reuptake inhibitors, SSRI, and tricyclic antidepressants, significantly improved depressive symptoms. DOP and SSRI had good efficacy and improved symptoms considerably in dPD, but the adverse effect of these agents was needed to follow closely.