Low-dose exogenous melatonin plus evening dim light and time in bed scheduling advances circadian phase irrespective of measured or estimated dim light melatonin onset time: preliminary findings

STUDY OBJECTIVES: The purpose of the present study was to preliminarily evaluate whether knowing the dim light melatonin onset (DLMO) time is advantageous when treating delayed sleep-wake phase disorder with low-dose melatonin treatment plus behavioral interventions (ie, evening dim light and time in bed scheduling). METHODS: In this randomized, controlled, double-blind trial, 40 adults with delayed sleep-wake phase disorder were randomly assigned to 4 weeks of 0.5 mg timed to be administered either 3 hours before the DLMO (measured DLMO group, n = 20) or 5 hours before sleep-onset time per actigraphy (estimated DLMO group, n = 20), in conjunction with behavioral interventions. The primary outcome was change in the DLMO (measured in-home). Secondary outcomes included sleep parameters per diary and actigraphy (sleep-onset and -offset times and total sleep time), Morningness-Eveningness Questionnaire, Multidimensional Fatigue Inventory, PROMIS-Sleep Disturbance, PROMIS-Sleep Related Impairment, and Pittsburgh Sleep Quality Index. Mixed-effects models tested for group differences in these outcome. RESULTS: After applying the Bonferroni correction for multiple comparisons (significant P value set at < .004), there were significant main effects for visit on all outcomes except for the Pittsburgh Sleep Quality Index and total sleep time per wrist actigraphy and diary. There were no group-by-visit interactions for any of the outcomes (P > .004). CONCLUSIONS: Scheduled low-dose melatonin plus behavioral interventions may improve many circadian and sleep parameters regardless of whether melatonin administration is scheduled based on estimated or measured DLMO. A larger-scale trial is needed to confirm these preliminary findings. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder; URL: https://clinicaltrials.gov/study/NCT03715465; Identifier: NCT03715465.