SLEEP - Repeated Melatonin Supplementation Improves Sleep in Hypertensive Patients Treated with Beta-Blockers: A Randomized Controlled Trial

VOLUME 35, ISSUE 10

MELATONIN SUPPLEMENTATION IMPROVES SLEEP IN PATIENTS ON BETA-BLOCKERS
Repeated Melatonin Supplementation Improves Sleep in Hypertensive Patients Treated with Beta-Blockers: A Randomized Controlled Trial

http://dx.doi.org/10.5665/sleep.2122

Frank A.J.L. Scheer, PhD¹^,²; Christopher J. Morris, PhD¹^,²; Joanna I. Garcia, BA¹; Carolina Smales, BSc¹; Erin E. Kelly, MSc¹; Jenny Marks, MPH¹; Atul Malhotra, MD¹^,²; Steven A. Shea, PhD¹^,²^,³

¹Medical Chronobiology Program, Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts;; ²Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts;; ³Center for Research on Occupational and Evironmental Toxicology, Oregon Health – Science University, Portland, OR

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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 ClinicalTrials.gov, identifier: NCT00238108; trial name: Melatonin Supplements for Improving Sleep in Individuals with Hypertension; URL: http://www.clinicaltrials.gov/ct2/show/NCT00238108.

Citation:

Scheer FAJL; Morris CJ; Garcia JI; Smales C; Kelly EE; Marks J; Malhotra A; Shea SA. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. SLEEP 2012;35(10):1395-1402.