Effects of daridorexant on sleep architecture in Japanese patients with insomnia disorder: analysis of a phase II randomized controlled trial.
Level 2 - randomized trial
Secondary analysis of an individual randomized controlled trial
PubMed 41969977 · doi:10.1007/s41105-025-00628-2
What was done
This secondary analysis evaluated the effects of daridorexant on sleep continuity and architecture in 47 Japanese adults with insomnia disorder (mean age 50.4 ± 8.0 years). Participants underwent 10 nights of polysomnography (PSG) across 2-night blocks of baseline, placebo, daridorexant 10 mg, 25 mg, and 50 mg. Measured outcomes included latency to persistent sleep (LPS), total sleep time (TST), wake after sleep onset (WASO), number of persistent awakenings (NAW), and individual sleep stage durations (N1, N2, N3, and REM). The 8-hour sleep period was divided into quarters to assess temporal dynamics across the night, with dose-response trends evaluated using Jonckheere-Terpstra tests.
What was found
Significant dose-response relationships were observed for LPS (P = 0.004), TST (P < 0.001), WASO (P < 0.001), and NAW (P = 0.004). For sleep architecture changes from baseline, daridorexant showed dose-dependent reductions in N1 sleep time (P = 0.006) alongside dose-dependent increases in N2 (P = 0.049), N3 (P = 0.050), and REM sleep durations (P < 0.001). Quartile analysis showed 50 mg significantly reduced NAW in the first quarter of the night (P = 0.012), while 25 mg and 50 mg significantly increased REM sleep in both the first and fourth quarters (P < 0.05). Exact effect sizes and confidence intervals were not reported in the abstract.
Why it matters
These findings suggest that dual orexin receptor antagonism with daridorexant preserves and enhances deeper non-REM (N3) and REM sleep without suppressing physiological sleep stages, sustaining REM enhancement through the final quarter of the night.
Limits
The sample size was small (n = 47), and each treatment condition lasted only 2 nights, leaving long-term architectural stability unaddressed. The abstract omits exact point estimates, variance, daytime functional outcomes, and safety data. Findings from this Japanese cohort may not fully generalize to other populations.
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