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

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Abstract

Rationale

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.

Objectives

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

Methods

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.

Results

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.

Conclusions

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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Notes

  1. WRAIR Test Battery and Palm-PVT task design by D. Thorne, Palm & PC programs by J. Shapiro, contract technical support by D. Redmond, project concept by G. Belenky.

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Acknowledgments

Melatonin and matching placebo were provided by Ecological Formulas (a division of Cardiovascular Research Ltd., Concord, CA, USA). We are grateful to Thomas Molina, Jacqueline Muñoz, Jillian Canton, Heather Holly, Elisabeth Beam, Nicole Woodrick, Christina Suh, Carlo Legasto, Jessica Stroup, and Heather Gunn for their assistance with data collection and data management. We thank Louis Fogg, Ph.D., for statistical advice. This work was supported by a grant from the National Institutes of Health (R01 NR007677) awarded to C.I. Eastman. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Institute of Nursing Research. The National Institute of Nursing Research and the National Institutes of Health had no involvement in designing the study, data collection, data analysis, and interpretation, writing of the manuscript, nor in the decision to submit the manuscript for publication. The authors alone are responsible for the content and writing of the paper.

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The authors do not have any conflicts of interest to disclose.

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

    Stephanie J. Crowley & Charmane I. Eastman

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  1. Stephanie J. Crowley
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  2. Charmane I. Eastman
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Correspondence to Stephanie J. Crowley.

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Crowley, S.J., Eastman, C.I. Melatonin in the afternoons of a gradually advancing sleep schedule enhances the circadian rhythm phase advance. Psychopharmacology 225, 825–837 (2013). https://doi.org/10.1007/s00213-012-2869-8

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