Comparative Efficacy and Safety of Treatments for Parkinson's Disease With Depression: A Systematic Review and...

Depression is a common non-motor symptom of Parkinson's disease (PD) and substantially impairs patients' quality of life. This study aimed to compare the efficacy and safety of different interventions for depression in PD.

We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs) in patients with PD and depression. Databases were searched from inception to September 30, 2025. Treatment effects were estimated using standardized mean differences (SMDs) for efficacy and odds ratios (ORs) for safety. Surface Under the Cumulative Ranking Curve (SUCRA) values were used to rank interventions. The protocol was registered in PROSPERO (CRD420251245403).

This study included 51 RCTs involving 5100 patients and 42 intervention measures. Compared with placebo, citalopram (SMD = -0.99, 95% CI: -1.87 to -0.12) and primary motor cortex (M1) repetitive transcranial magnetic stimulation (rTMS) (SMD = -1.29, 95% CI: -1.93 to -0.64) significantly improved depressive symptoms with moderate-quality evidence. SUCRA rankings favored citalopram (0.831), M1 rTMS (0.825), pergolide (0.811), and supplementary motor area (SMA) + M1 rTMS (0.802), although rankings should be interpreted alongside direct statistical comparisons. Several treatments could not be included in the safety network because of insufficient connectivity. Citalopram, sertraline, rasagiline, methylphenidate, memantine, and trazodone were associated with higher withdrawal rates due to adverse events.

Our findings indicate that selective serotonin reuptake inhibitors (SSRIs), dopamine agonists, and rTMS suggest relative efficacy and an acceptable safety profile in treating PD with depression. However, given the limited evidence for several interventions, these findings should be interpreted cautiously and confirmed in larger, multicenter studies.