Prolonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial

doi:10.1016/j.parkreldis.2020.03.029

Parkinsonism & Related Disorders

Volume 75, June 2020, Pages 50-54

https://doi.org/10.1016/j.parkreldis.2020.03.029 Get rights and content

Highlights

•
Sleep disturbances are common and disabling symptoms in Parkinson's disease (PD).
•
Prolonged-release melatonin (PRM) is effective treatment for sleep disorders in PD.
•
PSQI decreased by 18.4% after 4 weeks of PRM treatment.

Abstract

Background

The present study was a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of prolonged-release melatonin (PRM) in Parkinson's disease (PD) patients with poor sleep quality.

Methods

PD patients with a global Pittsburgh Sleep Quality Index (PSQI) score > 5 were included. Patients were assessed using the PSQI, a rapid eye movement sleep behavior disorder screening questionnaire, the Epworth Sleepiness Scale, Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Quality of Life-39 (PDQ-39), and Unified Parkinson's Disease Rating Scale (UPDRS)-III at the beginning of the study and after 4 weeks of treatment with 2 mg of PRM. Partial correlation analysis was performed to investigate the relationship between PSQI score and the other scales.

Results

Thirty-four PD patients with poor sleep quality were enrolled and divided into 2 groups based on medication; PRM (n = 16) and placebo (n = 18). Regarding efficacy, PSQI was significantly improved in the PRM group compared to the control group. Improvement in the NMSS and PDQ-39 summary index were observed in the PRM but not in the placebo group; UPDRS-III score was not significantly changed in either group. PSQI improvement correlated with improvement in NMSS score and PDQ-39 summary index. Regarding safety, all enrolled subjects did not complain of side effects due to PRM.

Conclusion

PRM is an effective and safe treatment option for subjective sleep quality in PD patients and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life in PD patients.

Introduction

Sleep disturbance has been reported in up to 88%–98% of Parkinson's disease (PD) patients, and various sleep disorders, such as fragmented sleep, sleep initiation problems, daytime sleepiness, sleep maintenance problems, and rapid eye movement sleep behavior disorder (RBD) can present even before motor symptoms. Further, sleep disturbances independently affect the quality of life (QoL) of PD patients, but the efficacy of various medications including dopaminergic agents and hypnotics, is still controversial [1]. Moreover, in terms of safety, most hypnotics commonly used in clinics can cause side effects such as drowsiness, memory impairment, and unsteadiness [2].

Decreased secretion of melatonin and disrupted circadian rhythms were associated with abnormal sleep-wake cycles as well as motor and non-motor symptom (NMS) fluctuations in PD [3]. Therefore, melatonin could be effective for management of poor sleep quality in PD. Furthermore, melatonin is regarded as a safe medication based on previous studies [4]. In PD, two previous studies using immediate-release melatonin reported improvements in subjective sleep quality [5,6]. Prolonged-release melatonin (PRM, 2 mg) is widely used and could be beneficial in PD patients considering it contains a pharmaceutical vehicle which delays delivery of melatonin, somewhat mimicking a more physiologic release relative to the pharmacologic delivery afforded by immediate-release melatonin [4]. Therefore, we conducted a randomized, double-blind, placebo-controlled, multi-center trial to investigate the efficacy of PRM in PD patients with poor sleep quality.

Section snippets

Participants

This study was approved by the Institutional Review Board of each of the five participating hospitals, and written informed consent was obtained from all patients in the study. This trial was registered at ClinicalTrials.gov under the identifier NCT 03258294. PD patients with poor sleep quality were recruited from five university hospitals in Korea from January 2016 to July 2018. PD was diagnosed based on the United Kingdom Parkinson's Disease Brain Bank Criteria [7], and striatal dopaminergic

Enrollment and baseline data

This study included a total of 34 patients; sixteen patients were randomized to receive PRM and 18 to receive placebo. Five protocol violations occurred; in the PRM group, one subject did not keep a follow date, and one took a medication not allowed for the study; in the placebo group, 3 subjects had poor medication compliance. Demographic, clinical data, and prevalence of poor sleep quality at baseline did not differ between the 2 groups (Table 1).

Efficacy and safety of PRM in PD patients with poor sleep quality

After 4 weeks of treatment, PSQI score was

Discussion

This is the first randomized, double-blind, placebo-controlled study to evaluate the efficacy of PRM in PD patients with poor sleep quality. Results from the study showed that PRM was an effective and safe treatment for PD patients with poor sleep quality. Furthermore, improvement of sleep quality correlated with NMS and QoL in PD patients.

Global PSQI score was improved in the PRM group, especially in subcomponents of subjective sleep quality, sleep latency, and sleep disturbances. Considering

Acknowledgments

This work was funded by Kuhnil Pharmaceutical Company. The funding source was not involved in the design, analysis, interpretation of data, or publication of this paper.

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Short communicationProlonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial

Highlights

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Participants

Enrollment and baseline data

Efficacy and safety of PRM in PD patients with poor sleep quality

Discussion

Acknowledgments

Lancet (London, England)

Sleep Med.

Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review

Mov. Disord.

Circadian system - a novel diagnostic and therapeutic target in Parkinson's disease?

Mov. Disord. : official journal of the Movement Disorder Society

Prolonged-release melatonin for insomnia - an open-label long-term study of efficacy, safety, and withdrawal

Therapeut. Clin. Risk Manag.

Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease. A randomized, double blind, placebo-controlled study

J. Neurol.

Short communication
Prolonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial