Sletten TL, et al. - Researchers assessed if 0.5 mg melatonin combined with behavioral sleep-wake scheduling would be an efficacious treatment for improving sleep initiation in clinically diagnosed Delayed Sleep-Wake Phase Disorder (DSWPD) patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). They found that improved objective and subjective measures of sleep disturbances and sleep-related impairments was effectively achieved with melatonin treatment 1 hour prior to DBT combined with behavioral sleep-wake scheduling in DSWPD patients with delayed circadian phase relative to DBT. The sleep-promoting effects of melatonin combined with behavioral sleep-wake scheduling were suggested to be largely responsible.

Methods

• Researchers performed this randomized, placebo-controlled, double-blind clinical trial in an Australian outpatient DSWPD population.
• Following 1-week baseline, they randomized clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) to 4-week treatment with 0.5 mg fast-release melatonin or placebo 1 hour before DBT for at least 5 consecutive nights per week.
• Behavioral sleep-wake scheduling, consisting of bedtime scheduled at DBT, was given to all patients.
• Actigraphic sleep onset time was the primary outcome.
• They also assessed the following secondary outcomes: 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.

Results

• Registration of 307 participants was done between September 13, 2012 and September 1, 2014.
• Of these, 116 were randomized to treatment (intention-to-treat n=116; n=62 males; mean age, 29.0 years).
• Sleep onset in the melatonin group was reported 34 min earlier (95% confidence interval [CI] -60 to -8), relative to baseline and compared to placebo.
• Following melatonin treatment (52.8%) vs placebo (24.0%) (P < 0.05), the following impacts were seen: 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.
• No difference was seen between the groups in terms of the number of nights treatment was taken per protocol.
• No significant difference was observed between groups with respect to post-treatment DLMO assessed in a subset of patients (n=43).
• Light-headedness, daytime sleepiness, and decreased libido were reported as adverse events, although similar rates were found between treatment groups.