OBJECTIVES: The objective of this systematic review was to determine the clinical benefit of daridorexant in people with insomnia disorder

METHODS: Medline®, Embase® and Cochrane were searched via Ovid platform. In addition, clinicaltrials.gov, bibliographic searches were also performed to identify the relevant English studies. Randomized controlled trials (RCTs) including adults with insomnia, treated with daridorexant were included. Two reviewers independently searched for the publications and extracted data, with differences resolved through consensus. A meta-analysis using fixed-effects model was conducted to calculate pooled effect estimates with 95% confidence intervals (CI) for sleep-related outcomes.

RESULTS: The SLR identified three RCTs (n=2859) from two publications which were included in the evidence synthesis. Pooled analysis of RCTs reported that a significant dose-response relationship was found in the reduction of wake after sleep onset with daridorexant 25mg (mean difference [MD] -11.2, 95%CI -15 to -7.45, three RCTs), daridorexant 50mg (MD -21.37, 95%CI -26.06 to -16.68, two RCTs) and latency to persistent sleep with daridorexant 25mg (MD -7.75, 95%CI -11.25 to -4.25, three RCTs), daridorexant 50mg (MD -10.77, 95%CI -15.15 to -6.40, two RCTs) from baseline to 1 month, when compared to placebo. Similar favourable results were reported for total sleep time daridorexant 10mg (MD 14.23, 95%CI 7.08 to 21.39, two RCTs), daridorexant 25mg (MD 14.42, 95%CI 9.17 to 19.68, three RCTs), and daridorexant 50mg (MD 21.92, 95%CI 14.99 to 28.85, two RCTs). No significant difference was observed in terms of treatment-emergent adverse events with daridorexant 10mg (risk ratio [RR] 1.18, 95%CI 0.97 to 1.44, two RCTs) and daridorexant 50mg (RR 1.12, 95%CI 0.92 to 1.36, two RCTs) when compared to placebo.

CONCLUSIONS: Despite few limitations, this systematic review provides up-to-date evidence and confirms that daridorexant improved sleep outcomes in people with insomnia disorder. However, no difference was observed for treatment-emergent adverse events between the groups.