Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational...

Background Daridorexant, a dual orexin receptor antagonist (DORA), was recently approved in Japan for the treatment of insomnia. The drug has been shown to improve daytime functioning and has characteristics such as a lower risk of residual effects and rebound insomnia. Nevertheless, important exclusion criteria in clinical trials included patients with comorbid psychiatric disorders and those showing incomplete or insufficient responses to existing therapies. Therefore, this observational study assessed the effectiveness and safety of daridorexant in real-world settings for Japanese participants with insomnia beyond those evaluated in previous clinical trials. Methods The medical records of participants treated with daridorexant at three medical sites in Japan between December 2024 and May 2025 were reviewed. Participants were required to provide voluntary consent, to be 18 years or older, to be diagnosed with insomnia, and to have started daridorexant 50 mg treatment. They also needed an Athens Insomnia Scale (AIS) total score of 6 or higher. Participants with comorbid psychiatric disorders excluded from past clinical trials were also included in this study. Participants who did not comply with the dosage and administration instructions outlined in the package insert for daridorexant were excluded. The primary endpoint was the mean change in the AIS total score from baseline to week 4 of daridorexant treatment. The other endpoints included the percentage of participants achieving an AIS total score of 5 or lower after treatment and adverse events (AEs). Results Of 56 eligible participants for this study, 55 were included in the efficacy and safety analysis. Among the 55 participants, 36 (65.5%) were women, and the mean age was 43.4 years. Twenty-eight (50.9%) participants had moderate symptoms according to the AIS classification (mean AIS total score: 12.2), and all participants had comorbid psychiatric disorders. Twenty-eight (50.9%) were hypnotic-naïve, while the remaining 27 (49.1%) were taking some form of hypnotic medication, which included benzodiazepines (BZDs) (23.6%), DORAs (21.8%), and non-BZDs (18.2%). One participant in whom daridorexant treatment was discontinued prior to the AIS evaluation in week 4 was excluded from the AIS evaluation. The mean change in AIS total score from baseline was -6.0 (95% confidence interval (CI): -7.2, -4.8, p<0.001), and 46.3% (25/54) of the participants achieved an AIS total score of ≤5 after four weeks of daridorexant treatment. Improvements were also observed across all eight AIS items, including daytime function (AIS-7). Significant improvements in AIS scores were observed in the subgroup of participants with depression, anxiety disorder, and schizophrenia. Daridorexant improved the AIS total score regardless of prior hypnotic medications. Eight participants experienced nonserious treatment-emergent AEs (TEAEs). Conclusion This study provided valuable insights into the real-world characteristics of outpatients initiating daridorexant therapy and showed its clinical effectiveness for insomnia, even in participants with psychiatric disorders and those with prior treatment failure. Improvements in daily function and a favorable safety profile were also observed in this participant population. These findings should be interpreted with caution, given the study's limitations, including a small sample size (n=54), short follow-up (four weeks), single-arm, and pre-post observational design.