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 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 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 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 two 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 one, two, 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 one participant taking lemborexant 5 mg and three 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 long-term use. This is important because most sleep medications work well initially, but patients then run into problems with tolerance. As reported, 55 percent 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 cognitive behavioral therapy and are not good candidates for existing sedative-hypnotics.
For more information, see the topic Insomnia in Adults in DynaMed®.
EBM Focus articles provide concise summaries of clinical trials most likely to inform clinical practice curated by the DynaMed editorial team.