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Psychopharmacology (Berl). 2013 Feb;225(4):825-37. doi: 10.1007/s00213-012-2869-8. Epub 2012 Sep 22.

Melatonin in the afternoons of a gradually advancing sleep schedule enhances the circadian rhythm phase advance.

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Biological Rhythms Research Laboratory, Department of Behavioral Sciences, Rush University Medical Center, 1645 West Jackson Blvd. Suite 425, Chicago, IL 60612, USA.



We test methods to advance (shift earlier) circadian rhythms without producing misalignment between rhythms and sleep. We previously tested (1) a gradually advancing sleep/dark schedule plus morning bright light and afternoon/evening melatonin and (2) the same sleep schedule with only morning bright light. Now we report on the same sleep schedule with only afternoon/evening melatonin.


This study aims to examine phase advances, sleepiness, and performance in response to melatonin compared to placebo.


Twelve adults (five female individuals) aged 20-45 years (mean ± SD = 28.3 ± 7.3 years) completed this within-subjects placebo-controlled counterbalanced study. The participants slept on fixed 8-h sleep schedules for nine days. Then, sleep/dark was advanced by 1 h/day for three consecutive days of treatment. The participants took 3 mg of melatonin or placebo 11 h before baseline sleep midpoint (the optimal time to produce phase advances) on the first treatment day and 1 h earlier on each subsequent day. We measured the dim light melatonin onset before and after treatment. The participants rated subjective symptoms throughout the study. They completed the Psychomotor Vigilance Task and rated sleepiness from 1 h before pill ingestion until bedtime on each treatment day.


Melatonin produced significantly larger advances (1.3 ± 0.7 h) compared to placebo (0.7 ± 0.7 h); however, in the hours between melatonin ingestion and bed, melatonin caused sleepiness and performance decrements.


Adding afternoon/evening melatonin to the gradually advancing sleep schedule increased the phase advance, but given the side effects, like sleepiness, it is better to use morning bright light and perhaps a lower dose of melatonin.

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