January 01, 2020
By Will Boggs MD
NEW YORK (Reuters Health) - Lemborexant improves sleep onset and sleep maintenance in older adults with insomnia disorder, according to findings from the SUNRISE1 trial.
"Based on the results of this study and the long-term efficacy and safety study, lemborexant appears to be a therapeutic option to consider," Dr. Margaret Moline from Eisai Inc., in Woodcliff Lake, New Jersey, told Reuters Health by email. "Since it is a dual orexin receptor antagonist, it works differently than many other prescription medications; therefore, it may be an option for patients who require an alternative to their current treatment."
An estimated 30% to 48% of elderly adults have insomnia symptoms, and the prevalence of insomnia disorder (difficulty initiating and/or maintaining sleep three nights or more per week for three months or longer) is as high as 20%, Dr. Moline and her colleagues note in JAMA Network Open.
Most of the pharmacologic agents indicated for the treatment of insomnia disorder are associated with significant risks for use in older adults.
In an earlier phase-2 study, lemborexant improved objective and subjective sleep measures with minimal next-morning residual sleepiness in adult and elderly participants with insomnia disorder.
In the current phase-3 trial, Dr. Moline and colleagues evaluated the efficacy and tolerability of lemborexant versus placebo or the active comparator zolpidem tartrate extended-release in 869 women 55 years and older and 137 men 65 years and older who met criteria for insomnia disorder.
The mean time to persistent sleep, as measured by polysomnography (PSG), decreased to a significantly greater extent with both the 5-mg and 10-mg doses of lemborexant than with either placebo or zolpidem.
Sleep efficiency also improved significantly more with both doses of lemborexant than with either placebo or zolpidem.
The amount of time spent awake after sleep onset (WASO) was significantly shorter with both doses of lemborexant than with either placebo or zolpidem.
These significant differences emerged within the first two nights of therapy and persisted through nights 29 and 30 of the study.
At the end of the first month, both doses of lemborexant were associated with significantly improved Insomnia Severity Index total scores and daily-functioning scores, compared with placebo. But score improvements did not differ significantly between the lemborexant groups and the zolpidem group.
The overall incidence of treatment-emergent adverse events was similar across treatment groups, and there was no evidence of withdrawal after discontinuation of lemborexant.
"Notably, in SUNRISE 1, the reduction in time spent awake - approximately 45 minutes overall with lemborexant - was mostly in the second half of the night, a common time when people with sleep maintenance complaints experience difficulty staying asleep," Dr. Moline said.
"Furthermore, lemborexant provided an improvement in sleep efficiency that translated into more than 60 minutes more sleep per night for patients than prior to treatment, which is a meaningful improvement for people with insomnia," she said.
Dr. Michael A. Grandner of the University of Arizona, in Tucson, who wrote a linked editorial, told Reuters Health by email, "Cognitive Behavioral Therapy for Insomnia is still the recommended first-line treatment for insomnia, and for older adults, it should probably be offered if available. But it is not always available or feasible, and in some older adults, it may not be effective. In these cases, a dual orexin receptor antagonist may be an option to consider for older adults who meet criteria for an insomnia disorder."
"Insomnia disorder is a condition worth treating in older adults," he said. "Even when recommended treatment is not available, medications may be a viable option. Among older adults, for whom the side effects of more sedative medications are particularly problematic, many physicians are turning to off-label, often ineffective, solutions. Before going this route, physicians may wish to consider (Food and Drug Adminitration)-indicated medications that do demonstrate efficacy and do not carry the same risks."
Dr. Grandner added, "If an older adult meets the diagnostic criteria for insomnia disorder, it is likely not a consequence of normal aging. It is likely a treatable problem that can be made to be manageable. And since insomnia disorder is likely a result of a conditioned arousal, the original precipitant (such as pain or medical problems or stress) becomes less active of a contributor to the insomnia condition. For this reason, if a patient meets criteria for insomnia, it should be treated as a comorbid condition and not just a symptom."
Dr. Kotaro Hatta of Juntendo University Nerima Hospital, in Tokyo, who recently demonstrated that suvorexant, another orexin-receptor antagonist, is effective for delirium prevention in older patients admitted for acute care, told Reuters Health by email, "The superiority of lemborexant not only to placebo but also to zolpidem tartrate extended-release with respect to both latency to persistent sleep and sleep maintenance is most interesting."
"I would expect lemborexant to fit in the management of insomnia in older patients at risk for delirium like the preceding dual orexin antagonist suvorexant," he said.
The U.S. Food and Drug Administration approved lemborexant for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults on December 23, 2019.
Eisai Inc. funded the study, employed most of the authors and had various relationships with the rest.
SOURCE: https://bit.ly/2ZCyiO4 JAMA Network Open, online December 27, 2019.
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