The Effectiveness of Melatonin for Sleep Disturbances in Parkinson' Disease: Systematic Review and Meta‐Analysis

Sleep disturbances in Parkinson's disease (PD) reduce quality of life. Melatonin, a sleep-wake hormone, shows treatment potential. However, its efficacy in PD remains unclear due to inconclusive findings across studies, warranting a systematic review to synthesise the available evidence. We searched PubMed, Cochrane, Web of Science, and Scopus for RCTs up to May 2025. Study quality was evaluated using the Cochrane Rob-2 tool. Statistical analysis was conducted using Review Manager version 5.4.1 with outcomes expressed as mean differences (MD) with 95% confidence intervals (CI). Out of eight studies with 409 PD patients, seven studies entered a meta-analysis that showed melatonin improved sleep quality and insomnia, as indicated by Pittsburgh Sleep Quality Index (PSQI) (MD = -1.75 [-2.94 to -0.55]; p = 0.004) and Epworth Sleepiness Scale (ESS) (MD = -1.07 [-1.87 to -0.27]; p = 0.009). Melatonin showed no significant impact on objective sleep parameters. However, sleep onset latency (MD = -9.74 [-17.47 to -2.02]; p = 0.001) and total sleep time (SMD = 0.84 [0.47 to 1.21]; p < 0.00001) improved, favouring melatonin, after adjusting for heterogeneity. Melatonin did not significantly change REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ) (MD = 0.71 [-0.44 to 1.86]; p = 0.23). No significant differences was found between melatonin and clonazepam in ESS (MD = -2.65 [-5.36 to 0.06]; p = 0.06). In conclusion, melatonin is a well-tolerated treatment that improves sleep quality, sleep onset latency, and total sleep time in PD. However, improvements in subjective sleep quality assessments did not meet minimal clinically important difference, which limits the clinical significance of these findings. Additional research is required to determine whether these benefits translate to other objective sleep parameters.