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Study Objectives: We conducted a retrospective study to investigate the efficacy and safety of switching from other hypnotics, including benzodiazepines and Z-drugs, suvorexant, ramelteon, mirtazapine, trazodone, and antipsychotics, to lemborexant, a dual orexin receptor antagonist, for 3 months., Methods: Clinical data obtained from the medical records of 61 patients treated at the Horikoshi Psychosomatic Clinic between December 2020 and February 2022 were analyzed, including the Athens Insomnia Scale, Epworth Sleepiness Scale, and Perceived Deficits Questionnaire-5. The primary outcome was the mean change in Athens Insomnia Scale score after 3 months. Secondary outcomes were the mean changes in the Epworth Sleepiness Scale and Perceived Deficits Questionnaire-5 scores over 3 months. We also compared pre- and post-diazepam equivalents., Results: The mean Athens Insomnia Scale score decreased over 3 months after switching to lemborexant (1 mo: -2.98 ± 5.19, P < .001; 2 mo: -3.20 ± 5.64, P < .001; 3 mo: -3.38 ± 5.61, P < .001). Mean Epworth Sleepiness Scale score did not change from baseline to 1 month (-0.49 ± 3.41, P = 0.27), 2 months (0.082 ± 4.62, P  = .89), or 3 months (-0.64 ± 4.80, P  = .30). Mean Perceived Deficits Questionnaire-5 score did improve from baseline to 1 month (-1.17 ± 2.47, P  = .004), 2 months (-1.05 ± 2.97, P  = .029), and 3 months (-1.24 ± 3.06, P  = .013). There was also a reduction in the total diazepam equivalent (baseline vs 3 mo: 14.0 ± 20.2 vs 11.3 ± 20.6, P < .001)., Conclusions: Our study showed that, by switching to lemborexant from other hypnotics, the risks associated with benzodiazepines and Z-drugs may be reduced., Citation: Horikoshi S, Miura I, Suzuki Y, et al. Switching to lemborexant for the management of insomnia in mental disorders: the SLIM study. J Clin Sleep Med . 2023;19(10):1753-1758., (© 2023 American Academy of Sleep Medicine.)

Study Objectives: The safety profile of the dual orexin receptor antagonists (DORAs) are currently unknown with regard to nocturnal responsivity among people with insomnia. We compared the auditory awakening thresholds (AATs) of the DORA suvorexant (10 and 20 mg) versus placebo in 12 individuals with DSM-5 insomnia., Methods: The study used a double-blind, placebo-controlled, three-way crossover design. Participants were randomly assigned to a treatment sequence that included placebo, suvorexant 10 mg, and suvorexant 20 mg. At the time of maximum drug concentration, auditory tones were played during stable stage N2 sleep. Tones increased by 5-decibel (db) increments until the participant awakened. The db at awakening was recorded as the AAT and compared between conditions. The proportion of awakenings higher than 85 db was also compared between conditions. Finally, sensitivity analyses were also conducted using surrounding thresholds (80 db and 90 db)., Results: The mean AAT did not differ significantly between either dose of suvorexant compared to placebo. Moreover, the proportions of individuals who remained asleep at the AAT 85 db cutoff did not differ across conditions. In addition, wake after sleep onset decreased and total sleep time increased in the suvorexant 20 mg condition compared to placebo., Conclusions: Suvorexant (10 and 20 mg) preserved the ability to respond to nocturnal stimuli, whereas the 20-mg dose improved the sleep of people with insomnia. This suggests that DORAs such as suvorexant can effectively treat insomnia while allowing patients to awaken to nocturnal stimuli in the environment., Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: A Phase IV 3-Way Double-blind, Randomized, Crossover Study to Compare the Awakening Threshold Effects (Responsivity) of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs; Identifier NCT03312517; URL: https://clinicaltrials.gov/ct2/show/NCT03312517., Citation: Drake CL, Kalmbach DA, Cheng P, Roth T, Tran KM, Cuamatzi-Castelan A, Atkinson R, SinghM, Tonnu CV, Fellman-Couture C. Can the orexin antagonist suvorexant preserve the ability to awaken to auditory stimuli while improving sleep? J Clin Sleep Med. 2019;15(9):1285-1291., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: Current pharmacological options for the treatment of insomnia insufficiently meet the needs of all insomnia patients. Approved treatments are not consistently effective in improving sleep onset and sleep maintenance, while also having complicated safety profiles. These limitations highlight the unmet need for additional medications and treatment strategies. Initial research suggests that the dual orexin receptor antagonists (DORAs) may offer an additional pharmaceutical option to treat insomnia in some patients., Methods: We reviewed the existing literature on dual orexin receptor antagonists in PubMed databases using the search terms "orexin receptor antagonist," "almorexant" "filorexant," "lembroexant" and "suvorexant"; searches were limited to English language primary research articles, clinical trials, and reviews., Results: Targeting the orexin receptor system for treatment of insomnia offers an additional and alternative pharmacological approach to more common gamma aminobutyric acid agonist sedative hypnotic treatment. Effectiveness is not well established in the current literature; however, the literature does suggest efficacy. Preclinical reports also suggest the potential for treatment in individuals with comorbid Alzheimer disease and insomnia., Conclusions: DORAs offer an additional treatment option for insomnia. More clinical trials are needed to robustly evaluate their safety and effectiveness in several subclasses of individuals with insomnia. Given the published literature, head-to-head comparisons to existing treatment for insomnia are warranted., (© 2018 American Academy of Sleep Medicine.)

Study Objectives: To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment., Methods: Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy assessments included a utility function that combined efficacy (SE) and safety (residual morning sleepiness as measured by Karolinska Sleepiness Scale [KSS]), PSG measures, and sleep diary. Safety assessments included KSS, Digit Symbol Substitution Test, computerized reaction time tests, and adverse events (AEs)., Results: A total of 616 subjects were screened; 291 were randomized. Baseline characteristics were similar between lemborexant groups and placebo (∼63% female, median age: 49.0 years). The study was stopped for early success after the fifth interim analysis when the 15-mg dose met utility index/KSS criteria for success; 3 other doses also met the criteria. Compared with placebo, subjects showed significant improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the beginning and end of treatment for lemborexant doses ≥ 5 mg ( P < .05). WASO and subjective WASO showed numerically greater improvements for doses > 1 mg. AEs, mostly mild to moderate, included dose-related somnolence., Conclusions: Lemborexant doses ranging from 2.5-10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness., Clinical Trial Registration: Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01995838; Identifier: NCT01995838., (© 2017 American Academy of Sleep Medicine)