title: Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, parallel-group design.
  
  
  METHODS
  Clinical and Translational Research Center at Brigham and Women's Hospital, Boston.
  
  
  METHODS
  Sixteen hypertensive patients (age 45-64 yr; 9 women) treated with the beta-blockers atenolol or metoprolol.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  his 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.
authors.affiliation: Medical Chronobiology Program, Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. fscheer@rics.bwh.harvard.edu
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Morris
authors.forename: Joanna I
authors.initials: JI
authors.lastname: Garcia
authors.forename: Carolina
authors.initials: C
authors.lastname: Smales
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kelly
authors.forename: Jenny
authors.initials: J
authors.lastname: Marks
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.forename: Steven A
authors.initials: SA
authors.lastname: Shea
mesh_terms: D056044:Actigraphy; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000319:Adrenergic beta-Antagonists; D008550:Melatonin