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

Overview

Journal J Clin Sleep Med

Specialties Neurology
Psychiatry

Date 2024 Mar 6

PMID 38445651

Authors

Leslie M Swanson

Trevor de Sibour

Kelley DuBuc

Deirdre A Conroy

Greta B Raglan

Kate Lorang

Jennifer Zollars

Shelley Hershner

J Todd Arnedt

Helen J Burgess

Affiliations

Soon will be listed here.

Abstract

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 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 ( > .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.

Citation: Swanson LM, de Sibour T, DuBuc K, et al. 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. . 2024;20(7):1131-1140.

References

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

Buysse D, Reynolds 3rd C, Monk T, BERMAN S, Kupfer D . The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989; 28(2):193-213. DOI: 10.1016/0165-1781(89)90047-4. View

Morgenthaler T, Lee-Chiong T, Alessi C, Friedman L, Aurora R, Boehlecke B . Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. 2007; 30(11):1445-59. PMC: 2082098. DOI: 10.1093/sleep/30.11.1445. View

Watson L, Phillips A, Hosken I, McGlashan E, Anderson C, Lack L . Increased sensitivity of the circadian system to light in delayed sleep-wake phase disorder. J Physiol. 2018; 596(24):6249-6261. PMC: 6292803. DOI: 10.1113/JP275917. View

Uchiyama M, Okawa M, Shibui K, Kim K, Tagaya H, Kudo Y . Altered phase relation between sleep timing and core body temperature rhythm in delayed sleep phase syndrome and non-24-hour sleep-wake syndrome in humans. Neurosci Lett. 2000; 294(2):101-4. DOI: 10.1016/s0304-3940(00)01551-2. View

Voultsios A, Kennaway D, Dawson D . Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythms. 1997; 12(5):457-66. DOI: 10.1177/074873049701200507. View

Nagtegaal J, Kerkhof G, Smits M, Swart A, van der Meer Y . Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res. 1998; 7(2):135-43. DOI: 10.1046/j.1365-2869.1998.00102.x. View

Nagtegaal J, Laurant M, Kerkhof G, Smits M, van der Meer Y, Coenen A . Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome. J Psychosom Res. 2000; 48(1):45-50. DOI: 10.1016/s0022-3999(99)00075-6. View

Rajaratnam S, Licamele L, Birznieks G . Delayed sleep phase disorder risk is associated with absenteeism and impaired functioning. Sleep Health. 2017; 1(2):121-127. DOI: 10.1016/j.sleh.2015.03.001. View

10.

Duffy J, Cain S, Chang A, Phillips A, Munch M, Gronfier C . Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc Natl Acad Sci U S A. 2011; 108 Suppl 3:15602-8. PMC: 3176605. DOI: 10.1073/pnas.1010666108. View

11.

Horne J, Ostberg O . A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976; 4(2):97-110. View

12.

Oren D, Turner E, Wehr T . Abnormal circadian rhythms of plasma melatonin and body temperature in the delayed sleep phase syndrome. J Neurol Neurosurg Psychiatry. 1995; 58(3):379. PMC: 1073383. DOI: 10.1136/jnnp.58.3.379. View

13.

Benloucif S, Burgess H, Klerman E, Lewy A, Middleton B, Murphy P . Measuring melatonin in humans. J Clin Sleep Med. 2008; 4(1):66-9. PMC: 2276833. View

14.

Auger R, Burgess H, Emens J, Deriy L, Sharkey K . Do Evidence-Based Treatments for Circadian Rhythm Sleep-Wake Disorders Make the GRADE? Updated Guidelines Point to Need for More Clinical Research. J Clin Sleep Med. 2015; 11(10):1079-80. PMC: 4582047. DOI: 10.5664/jcsm.5072. View

15.

Sletten T, Magee M, Murray J, Gordon C, Lovato N, Kennaway D . Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Med. 2018; 15(6):e1002587. PMC: 6005466. DOI: 10.1371/journal.pmed.1002587. View

16.

Burgess H, Revell V, Molina T, Eastman C . Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab. 2010; 95(7):3325-31. PMC: 2928909. DOI: 10.1210/jc.2009-2590. View

17.

van Geijlswijk I, Korzilius H, Smits M . The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep. 2010; 33(12):1605-14. PMC: 2982730. DOI: 10.1093/sleep/33.12.1605. View

18.

Watanabe T, Kajimura N, Kato M, Sekimoto M, Nakajima T, Hori T . Sleep and circadian rhythm disturbances in patients with delayed sleep phase syndrome. Sleep. 2003; 26(6):657-61. DOI: 10.1093/sleep/26.6.657. View

19.

Yu L, Buysse D, Germain A, Moul D, Stover A, Dodds N . Development of short forms from the PROMIS™ sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2012; 10(1):6-24. PMC: 3261577. DOI: 10.1080/15402002.2012.636266. View

20.

Sasseville A, Paquet N, Sevigny J, Hebert M . Blue blocker glasses impede the capacity of bright light to suppress melatonin production. J Pineal Res. 2006; 41(1):73-8. DOI: 10.1111/j.1600-079X.2006.00332.x. View