Kate Johnson

June 15, 2011

June 15, 2011 (Minneapolis, Minnesota) — Melatonin supplementation can significantly improve sleep disturbances in hypertensive men treated with β-blockers, according to a randomized, double-blind, placebo-controlled trial presented here at SLEEP 2011, the 25th anniversary meeting of the Associated Professional Sleep Societies.

The results may have implications for other populations treated with β-blockers, as well as people with decreased melatonin production for other reasons, such as spinal cord injury, said Frank Scheer, PhD, from Harvard Medical School and Brigham and Women’s Hospital in Boston.

"There's an estimated 2 million people just in the US treated with β-blockers, not just for hypertension but for arrhythmias, angina, post-MI [myocardial infarction], congestive heart failure, migraine, post-traumatic stress disorder, and generalized anxiety disorder," said Dr. Scheer. "In addition, patients with spinal cord injury at the cervical level, which transects the projection from the SCN [suprachiasmatic nuclei] to the pineal gland, do not produce any melatonin."

Reduction of Melatonin

Previous research has demonstrated that atenolol, a selective β-receptor antagonist, at a typical dose of 50 mg, can substantially reduce night-time production of melatonin in healthy persons — with a 100-mg dose also increasing awake time during the night, said Dr. Scheer.

The addition of melatonin, 5 mg, can restore sleep quality in such people, he said.

Previous work by his group has also shown that in unmedicated hypertensive men, prolonged melatonin supplementation, at a dose of 2.5 mg nightly, can significantly improve sleep measures.

The current study examined the same dose of melatonin in 15 hypertensive patients (aged 45 to 64 years; 9 women) who were being treated with atenolol or metoprolol.

Extensive medical and sleep screening was done to ensure that there were no comorbid conditions, including sleep disorders, and all participants were required to refrain from using alcohol, nicotine, caffeine, and other drugs for 2 weeks before and during the study.

Participants were randomly assigned to receive melatonin, 2.5 mg, or placebo 1 hour before bedtime for 3 to 4 weeks. They were also required to maintain a strict 8 hours in bed for the duration of the study.

"This is a dose we feel leads to physiologic levels of melatonin for 6 to 8 hours, spanning the majority of the 8-hour sleep opportunity," said Dr. Scheer.

For the main outcome measure, which was difference from baseline in polysomnographic measurements of total sleep time, sleep efficiency, and sleep-onset latency, participants treated with melatonin had significantly greater improvements compared with controls.

Specifically, compared with controls, those treated with melatonin had a total sleep time that was 37 minutes longer and sleep efficiency that was 8% better; stage 1 sleep onset decreased by 8 minutes (P = .007), and stage 2 onset decreased by 14 minutes (P = .001).

Total Sleep Time and Sleep Efficiency by Treatment

End Point Melatonin Placebo P Value
Total sleep time (min) 424 387 .046
Sleep efficiency (%) 88 81 .046

For a secondary outcome measure of actigraphy, melatonin was shown to significantly improve total sleep time compared with placebo (390 minutes vs 377 minutes; P = .011) and to improve sleep efficiency (81% vs 78%; P = .007).

Viable Approach

"I think it’s a viable way to help patients with hypertension," said Rachel Markwald, PhD, moderator of the session and a neuroscientist at the University of Colorado, Boulder.

"Melatonin is proven to be a safe alternative to taking hypnotics," she told Medscape Medical News.

"There have not been any adverse events reported with chronic melatonin supplementation — and we're actually getting at something that is being disrupted with the medication. It's not going to hurt. I am not a clinician but if I were I would want to explore it."

Dr. Scheer and Dr. Markwald have disclosed no relevant financial relationships.

The 25th anniversary meeting of the Associated Professional Sleep Societies. Abstract #O471. Presented June 14, 2011.


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