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Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial

Sletten, TL, Magee, M, Murray, JM, Gordon, CJ, Lovato, N, Kennaway, DJ, Gwini, SM, Bartlett, DJ, Lockley, SW, Lack, LC, Grunstein, RR and Rajaratnam, SMW 2018, Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial, PLoS Medicine, vol. 15, no. 6, pp. 1-24, doi: 10.1371/journal.pmed.1002587.

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Title Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial
Author(s) Sletten, TL
Magee, M
Murray, JM
Gordon, CJ
Lovato, N
Kennaway, DJ
Gwini, SMORCID iD for Gwini, SM orcid.org/0000-0002-0295-4575
Bartlett, DJ
Lockley, SW
Lack, LC
Grunstein, RR
Rajaratnam, SMW
Journal name PLoS Medicine
Volume number 15
Issue number 6
Article ID e1002587
Start page 1
End page 24
Total pages 24
Publisher PLOS
Place of publication San Francisco, CA
Publication date 2018-06-18
ISSN 1549-1277
1549-1676
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
PLACEBO-CONTROLLED TRIAL
CIRCADIAN PHASE
EXOGENOUS MELATONIN
ONSET INSOMNIA
SOCIAL JETLAG
LIGHT
METAANALYSIS
RHYTHM
HUMANS
BENZODIAZEPINES
Delayed Sleep on Melatonin (DelSoM) Study Group
Summary Background: Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). Methods: This randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time. Findings: Between September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] −60 to −8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm. Conclusions: In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling. Trial registration: This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897.
Language eng
DOI 10.1371/journal.pmed.1002587
Indigenous content off
Field of Research 11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, Sletten et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136134

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.