Exploring the role of melatonin in managing sleep and motor symptoms in Parkinson's disease: a pooled analysis of double-blinded randomized controlled trials.

Background: Parkinson's disease (PD), a progressive neurodegenerative disorder, often involves sleep disturbances, affecting 88-98% of patients. Melatonin, a sleep-regulating neurohormone, shows the potential to improve sleep quality and non-motor symptoms in PD.

Objective: To evaluate melatonin's efficacy and safety in PD patients with sleep disorders.

Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane till January 2025. The risk of bias in the included studies was evaluated using the Cochrane risk-of-bias tool. Dichotomous outcomes were expressed as risk ratios (RRs) with 95% confidence intervals (CIs), while continuous outcomes were reported as mean differences (MDs) with 95% CIs.

Results: We retrieved 2537 records. Five double-blinded RCTs were finally included. The meta-analysis revealed a significant improvement in sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), in the melatonin group compared to placebo (MD= -1.88, 95% CI: [-3.07, -0.68], P = 0.002). However, no significant differences were observed for the Epworth Sleepiness Scale (MD= -1.04 CI: [-2.81, 0.73], P = 0.25), total sleep time (MD = 14.85 min CI: [-5.45, 35.16], P = 0.15), sleep efficiency, sleep latency, REM sleep latency, frequency of arousals, or REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ; MD = 0.74, P = 0.50). For Parkinson's disease-related outcomes, melatonin significantly improved Non-Motor Symptom Scale (NMSS) scores but showed no significant effects on UPDRS Part III scores or Parkinson's Disease Quality of Life.

Conclusions: Melatonin improves subjective sleep quality and non-motor symptoms in PD patients with a favorable safety profile, but effects on objective measures and motor symptoms remain inconclusive. This meta-analysis was registered on PROSPERO. Background: CRD42024619496.