Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease: A randomised controlled trial

BACKGROUND: Melatonin may reduce REM‐sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. OBJECTIVE: To assess the efficacy of prolonged‐release (PR) melatonin for RBD in PD. METHODS: Randomized, double‐blind, placebo‐controlled, parallel‐group trial with an 8‐week intervention and 4‐week observation pre‐ and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged‐release melatonin (Circadin) or matched placebo, ingested orally once‐daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed‐model analysis of variance (n = 15 per group). RESULTS: No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = −3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). CONCLUSION: Prolonged‐release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.