Reference: JAMA Netw Open. 2019 Dec 2;2(12)
Insomnia is a common and debilitating disorder defined by sleep difficulties occurring for more than three nights per week for at least three months. Cognitive behavioral therapy (CBT) is the first-line management approach for insomnia, partly because of side effects and long-term efficacy issues seen with sedative-hypnotics. The American Academy of Sleep Medicine and the American Geriatric Society recommend restricting or avoiding the use of sedative-hypnotics in older adults, a population particularly prone to insomnia, due to potential adverse effects such as falls and injuries. Orexin A and orexin B hormones regulate arousal and wakefulness; dual orexin receptor antagonists such as lemborexant have therefore been proposed as alternatives to existing medications.
The SUNRISE 1 trial was a randomized double-blind phase 3 trial conducted in 67 sites in North America and Europe. A total of 1,006 adults (women 55 or older, men 65 or older) received placebo for two weeks followed by lemborexant 5 mg or 10 mg, zolpidem tartrate extended release 6.25 mg, or placebo for 30 days at bedtime. They had paired polysomnograms at baseline and during the first two and last two nights of treatment. Participants also completed sleep diaries throughout the study period, and were followed for about 2 weeks after treatment. Lemborexant significantly decreased polysomnogram-measured latency to persistent sleep, wake-after-sleep onset, and time spent awake, and increased sleep maintenance on treatment nights 1, 2, 29, and 30 compared with placebo and zolpidem. Participants taking lemborexant reported improved daily functioning and sleep efficiency compared with placebo but not zolpidem, while subjective sleep onset latency was reported to be improved with lemborexant compared to both placebo and zolpidem. Four falls occurred in the lemborexant 5 mg group, but the authors did not consider them drug-related. Sleep paralysis was also reported by 1 participant taking lemborexant 5 mg and 3 participants taking lemborexant 10 mg.
Although the SUNRISE 1 trial indicates that lemborexant may be more effective than placebo or zolpidem at improving insomnia in older adults for up to 30 days, this trial does not tell us whether it would be effective or safe for longer than that. This is important because most sleep medications work well at first but patients then run into problems with tolerance. As reported, 55% of study participants were between the ages of 55 and 64, which many would not consider a “geriatric” population. The study also reported complaints of drowsiness but did not measure it objectively. This metric was assessed in a prior study of this drug and was found to be a dose-dependent side effect. Since there has been an increase in motor vehicle accidents and falls reported with this class of drugs, and initial studies indicate that somnolence is the most common side effect, more detail is needed about safety. The differences observed between polysomnogram-measured and patient-reported sleep quality should also be examined further. Nevertheless, this trial provides initial evidence that lemborexant may be a useful medication option for older adults with insomnia who have failed CBT and are not good candidates for existing sedative-hypnotics.
For more information, see the topic Insomnia in Adults in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Terri Levine, PhD, Medical Writer in Obstetrics and Gynecology at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.