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

Delayed Sleep-Wake Phase Disorder (DSWPD) is a type of insomnia characterized by difficulty falling asleep at conventional times and difficulty waking for daytime commitments. Although not part of the diagnostic criteria, delayed circadian release of melatonin can underlie DSWPD. Melatonin has been suggested as a treatment for DSWPD, but clinical trials are lacking.

The Delayed Sleep on Melatonin (DelSoM) study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 outpatient centers in Australia. Participants were men and women (aged 16-65 years) with DSWPD and delayed dim light melatonin onset (defined as melatonin release any time after 30 minutes before the desired bedtime).

Methods

Participants were randomized to take a placebo or 0.5 mg fast-release melatonin (Pure Encapsulations, Sudbury, MA) 1-hour before their desired bedtime at least 5 nights a week for 4 weeks. The sleep-wake cycle was monitored with sleep diaries and wrist actigraphy. Participants also completed the Patient-Reported Outcomes Measurement Information System (PROMIS) daily. 

DSWPD characterized by difficulty falling asleep at conventional times and difficulty waking for daytime commitments.

Results

The primary outcome was actigraphic sleep onset time. Melatonin supplementation led to sleep onset that was 34 minutes earlier than baseline and 36 minutes earlier than placebo. Compared with placebo, melatonin also improved sleep efficiency during the first tertile of sleep and decreased sleep-related functional impairment. Sleep disturbance, insomnia severity, and functional disability decreased in the melatonin group. A greater proportion of patients showed clinician-rated improvement after melatonin treatment (53%) than placebo (24%). 

The improvement in time taken to fall asleep of 34-36 minutes with melatonin was considered to be clinically relevant. It was also clinically relevant that melatonin enhanced the behavioral intervention of going to bed at the ideal bedtime. Most participants did not take melatonin every night (the protocol was 5+ nights/week), showing that melatonin can be effective when taken sporadically. Finally, the 0.5-mg dosage was lower than previous studies (3-5 mg) yet sufficient to produce meaningful results.  

Conclusions

The authors of the study concluded that low-dose melatonin, combined with behavioral sleep-wake scheduling, is a safe and effective intervention for patients with DSWPD and confirmed circadian disruption. Melatonin improved objective and subjective sleep quality, daytime function, and clinical symptom severity. 

Sletten, T.L., Magee, M., Murray, J.M., Gordon, C.J., Lovato, N., Kennaway, D.J., … Delayed Sleep on Melatonin (DelSoM) Study Group. (2018). Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLOS Medicine, 15(6), e1002587.