As 2020 rolled in, so did a new drug for insomnia. Lemborexant (Dayvigo), a dual orexin receptor antagonist (DORA), became available after winning FDA approval in late December 2019 to treat insomnia with sleep onset or sleep maintenance difficulties.
The drug inhibits orexin signaling by binding to orexin receptor 1 (OX1R) and 2 (OX2R). When activated, OX1R is thought to suppress REM sleep; OX2R is thought to suppress non-REM and REM sleep.
The agency's approval was based on research including two pivotal phase III studies that evaluated lemborexant in about 2,000 adult patients with insomnia. The SUNRISE 1 trial tested 5- and 10-mg doses against zolpidem (Ambien) and placebo for 1 month in adults over age 55; SUNRISE 2 studied the same doses against placebo for 6 months in adults of all ages. Lemborexant bested placebo in sleep onset and sleep maintenance in both subjective and objective evaluations in these trials.
In older adults, most insomnia drugs are associated with significant risks like falling or cognitive decline, so there is a need for new treatment options in this population in particular, said Michael Grandner, PhD, of the University of Arizona in Tucson, who wasn't involved with the research.
For patients of all ages, the DORA class of drugs "packs less of a punch" than other agents in terms of efficacy but is associated with fewer side effects, Grander said at the 2020 virtual Psych Congress, where SUNRISE 2 data were presented. "Generally, the reason you would prescribe [lemborexant] is not because it works better or faster or longer, but because it is probably safer," he told 鶹ý. "This [study] shows that you're not sacrificing a ton of benefit for safety."
Research about investigational daridorexant, another DORA, also showed efficacy in treating insomnia this year. Compared with placebo, daridorexant at 25 mg and 50 mg significantly improved sleep onset and sleep maintenance from baseline, according to data from the first of two phase III randomized controlled trials presented at SLEEP 2020, the joint virtual meeting of the American Academy of Sleep Medicine and the Sleep Research Society. The drug also improved daytime functioning, an important secondary endpoint, reported Thomas Roth, PhD, of Henry Ford Health System in Detroit.
Sleep and the Pandemic
More than half the people surveyed in an online population study experienced serious sleep difficulties during the COVID-19 pandemic, though some may have had better sleep, Canadian researchers reported. "Our results suggest that the effects of the pandemic on sleep are more complex than just bad or good," said Rebecca Robillard, PhD, of the University of Ottawa, at SLEEP 2020.
"The pandemic involves a global external stressor with widespread consequences and for many, this leads to some degree of psychological distress, a phenomenon well known to interact with sleep," she noted.
The overall rate of any serious sleep difficulties, including initiating sleep, maintaining sleep, or waking too early, rose from 36% before the pandemic to 51% during it, Robillard reported. "We also observed that 8% of our sample reported an increase in the frequency of sleeping medication used during the outbreak," she said.
The pandemic also brought an unprecedented surge in telemedicine, and with that, interest in virtual visits for cognitive behavioral therapy (CBT). "We know that cognitive behavioral therapy for insomnia is a very effective treatment," said Deirdre Conroy, PhD, of the University of Michigan in Ann Arbor, at SLEEP 2020. "However, in pre-COVID days, we didn't use it quite often by telemedicine or phone; most of the research we have is based on face-to-face interactions."
Data from a randomized controlled noninferiority trial showed that patients with chronic insomnia reported no differences between telemedicine and face-to-face CBT in terms of overall satisfaction with treatment or the therapist's warmth and skills, Conroy reported.
"The outcomes from this study suggest that the rapport and confidence a patient has with their therapist over telemedicine did not differ from therapy delivered in person," she told 鶹ý. "This is especially important to consider as so much of our healthcare is now being delivered remotely during the pandemic."
Behavioral therapy emerged as a front-runner for first-line insomnia treatment in other trial data published this year: a similar proportion of insomnia patients responded to behavioral therapy and zolpidem (Ambien) as first-line therapy, but the proportion of responders diverged with second-line treatments.
Overall, about 25%-30% of insomnia patients did not respond, reported researcher Charles Morin, PhD, of the Université Laval in Quebec, Canada. "I think we moved one step further from where we were before, but we still don't have the answers for all patients with chronic insomnia," he said.
Consequences of not treating insomnia also were seen in novel research published this year, when doctoral candidate Shuai Yuan and Susanna Larsson, PhD, of Karolinska Institutet in Stockholm, identified insomnia as an independent risk factor for type 2 diabetes (OR 1.17, 95% CI 1.11-1.23) in a Mendelian randomization study.
Considering the large effect of obesity on type 2 diabetes and the increasing global burden of obesity, an emphasis on weight control is needed, the researchers said. But global prevention strategies also should be employed to mitigate other diabetes risk factors, they suggested, including bolstering sleep quality.