In January 2022, a new medication in the DORA class named daridorexant was approved by the FDA (Table 5).
Daridorexant, like its DORA counterparts, has been shown to have efficacy in improving subjective and objective markers of insomnia. This has included polysomnographic measures of wake after sleep onset and latency to persistent sleep, as well as subjective total sleep time. Importantly, in addition to positive sleep outcomes, improvements with daytime function have also been observed with this medication (Mignot E et al. Lancet Neurol. 2022;21[2]:125-39). Daridorexant’s half-life of approximately 8 hours is shorter than that of the other available DORAs, leading to fewer day-after effects. The combination of effectiveness for sleep initiation and maintenance without daytime impairment distinguishes daridorexant from the other DORAs and even other classes of sleep medication.
Courtesy ACCP
Dr. Michael Pelekanos
Safety, especially in patients of age 65 and older, is an important concern with sleep medication, particularly with respect to polypharmacy, over-sedation, increased fall risk, and cognitive impairment, but daridorexant’s available safety data suggest a favorable safety profile (Zammit G et al. Neurology. 2020;94[21]:e2222-32).
Daridorexant at the highest dose available, 50 mg, did not worsen respiratory function, in terms of the apnea-hypopnea index and oxygen saturation in individuals with mild-moderate obstructive sleep apnea regardless of sleep stage (Boof ML et al. Sleep. 2021;44[6]:zsaa275). However, more safety and longitudinal data are needed to have a fuller understanding of any potential limitations of this medication.
While we continue to recommend CBT-I as the first-line treatment whenever possible for patients with insomnia, not all patients have access to this treatment and not all patients will respond satisfactorily to it. Thus, pharmacologic treatment can continue to play an important role in the management of some patients’ insomnia. Each class of medications used for treating insomnia features a unique constellation of advantages and limitations, meaning that the more available options, the greater the chances of finding an option that will be both effective and safe for a particular patient. The growing DORA class, especially its newest available entrant, daridorexant, represents a continued expansion of the armamentarium of options against insomnia.
Dr. Pelekanos and Dr. Sum-Ping are with the Division of Sleep Medicine, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, California.