Objective: Test the efficacy of prolonged-released melatonin for REM sleep behaviour disorder (RBD) in Parkinson’s disease (PD).

Background: Half of all PD patients experience RBD with dream enactment, which can be frequently injurious. Currently, melatonin and clonazepam are the most recommended treatments for RBD. However, current recommendations are based on poor evidence from case-reports and small case series. Thus, there is a need for high quality evidence from randomized clinical trials to inform the guidelines.

Methods: A phase-II, randomised, double blind, placebo-controlled, parallel group trial with an 8-week intervention period and 4 weeks of observation before and after the intervention. 30 PD patients with RBD were randomized into one of two arms (1:1) to receive 4mg prolonged released melatonin (Circadin) or matched placebo (lactose monohydrate) ingested orally once daily within 1 hour of bedtime. The efficacy of melatonin was assessed as the difference in the mean total number of RBD events as captured by the “weekly CIRUS-RBD questionnaire”, which measures the frequency and severity of RBD symptoms using daily entries. The primary outcome was the aggregate of all incidents measured within weeks 5 to 8 of treatment compared to the 4 weeks prior to treatment.

Results: One participant dropped out after moving overseas and one participant with idiopathic RBD was mistakenly randomized as being diagnosed with PD at study inclusion. All data obtained were included in the mixed model analysis of variance (SAS 9.4). Adverse events were mild and included headaches, mild fatigue and morning sleepiness, (n=4 in treatment and n=5 on placebo). The dosage of one participant in the treatment arm had to be reduced to 2mg daily for 4 weeks during treatment due to light-headedness and fatigue in the morning, as per protocol. The primary outcome analysis revealed no significant reduction in RBD events per week between groups within weeks 5 to 8 of the protocol (3.6 events in the melatonin group vs. 3.4 in the placebo group; difference 0.2 events/week; 95% CI=-3.2 to 3.6 events; p=0.91).

Conclusions: Prolonged released melatonin does not alleviate RBD symptoms in patients with Parkinson’s disease using the protocol dosage scheme described.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-prolonged-release-melatonin-for-rem-sleep-behaviour-disorder-in-parkinsons-disease-a-double-blind-randomised-placebo-controlled-trial/