Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: A randomized controlled trial

Frank A.J.L. Scheer, Christopher J. Morris, Joanna I. Garcia, Carolina Smales, Erin E. Kelly, Jenny Marks, Atul Malhotra, Steven A. Shea

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Study Objectives: In the United States alone, approximately 22 million people take beta-blockers chronically. These medications suppress endogenous nighttime melatonin secretion, which may explain a reported side effect of insomnia. Therefore, we tested whether nightly melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers. Design: Randomized, double-blind, placebo-controlled, parallel-group design. Setting: Clinical and Translational Research Center at Brigham and Women's Hospital, Boston. Patients: Sixteen hypertensive patients (age 45-64 yr; 9 women) treated with the beta-blockers atenolol or metoprolol. Interventions: Two 4-day in-laboratory admissions including polysomnographically recorded sleep. After the baseline assessment during the first admission, patients were randomized to 2.5 mg melatonin or placebo (nightly for 3 weeks), after which sleep was assessed again during the second 4-day admission. Baseline-adjusted values are reported. One patient was removed from analysis because of an unstable dose of prescription medication. Measurements and Results: In comparison with placebo, 3 weeks of melatonin supplementation significantly increased total sleep time (+36 min; P = 0.046), increased sleep efficiency (+7.6%; P = 0.046), and decreased sleep onset latency to Stage 2 (-14 min; P = 0.001) as assessed by polysomnography. Compared with placebo, melatonin significantly increased Stage 2 sleep (+41 min; P = 0.037) but did not significantly change the durations of other sleep stages. The sleep onset latency remained significantly shortened on the night after discontinuation of melatonin administration (-25 min; P = 0.001), suggesting a carryover effect. Conclusion: In hypertensive patients treated with beta-blockers, 3 weeks of nightly melatonin supplementation significantly improved sleep quality, without apparent tolerance and without rebound sleep disturbance during withdrawal of melatonin supplementation (in fact, a positive carryover effect was demonstrated). These findings may assist in developing countermeasures against sleep disturbances associated with beta-blocker therapy. Clinical Trial Information: This study is registered with, identifier: NCT00238108; trial name: Melatonin Supplements for Improving Sleep in Individuals with Hypertension; URL: http://www.

Original languageEnglish (US)
Pages (from-to)1395-1402
Number of pages8
Issue number10
StatePublished - Oct 1 2012


  • Actigraphy
  • Adrenergic beta-antagonists
  • Atenolol
  • Autonomic nervous system
  • Hypertension
  • Hypnotics
  • Melatonin
  • Metoprolol
  • Polysomnography
  • Sleep

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)


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