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

Sleep. 2012 Oct 1;35(10):1395-402. doi: 10.5665/sleep.2122.


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: n 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: his study is registered with, identifier: NCT00238108; trial name: Melatonin Supplements for Improving Sleep in Individuals with Hypertension; URL:

Keywords: Actigraphy; adrenergic beta-antagonists; atenolol; autonomic nervous system; hypertension; hypnotics; melatonin; metoprolol; polysomnography; sleep.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actigraphy
  • Adrenergic beta-Antagonists / adverse effects*
  • Adrenergic beta-Antagonists / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Male
  • Melatonin / therapeutic use*
  • Middle Aged
  • Polysomnography
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep Initiation and Maintenance Disorders / chemically induced*
  • Sleep Initiation and Maintenance Disorders / drug therapy


  • Adrenergic beta-Antagonists
  • Melatonin

Associated data