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 (DSWPD) with low dose melatonin treatment plus behavioral interventions (i.e., evening dim light and time in bed (TIB) scheduling).

METHODS: In this randomized, controlled, double-blind trial, 40 adults with DSWPD 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 (MEQ), Multidimensional Fatigue Inventory (MFI), PROMIS-Sleep Disturbance (SD), PROMIS-Sleep Related Impairment (SRI), and Pittsburgh Sleep Quality Index (PSQI). 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 PSQI 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: Clinicaltrials.gov Identifier: NCT03715465; Name: The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder; URL: https://clinicaltrials.gov/study/NCT03715465.