Daridorexant: Comprehensive Review of A New Oral Agent for the Treatment of Insomnia

Objective: To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of daridorexant in patients with insomnia. Data Sources: A literature search of PubMed (March 1, 2018, to October 19, 2022) and ClinicalTrials.gov search was conducted using the following terms: daridorexant and ACT-541468. Additional articles were identified by hand from references. Study selection and data extraction: We included English-language articles evaluating daridorexant pharmacology, efficacy, or safety in humans for the management of insomnia. Data synthesis: Daridorexant has a peak plasma concentration of 1-2 hours, terminal half-life of 8 hours, and absolute bioavailability of 61%. Wake after sleep onset (WASO) significantly decreased from baseline to months 1 and 3 in daridorexant 25 (-18.40 and -22.97 min, P < 0.0001) and 50 mg (-28.98 and -29.41 min, P < 0.0001) groups compared with placebo. Latency to persistent sleep (LPS) significantly decreased from baseline to months 1 and 3 for daridorexant 25 mg (-28.17 and -30.73 min, P = 0.0005 and P = 0.0015) and 50 mg (-31.20 and -34.80 min, P < 0.0001). Relevance to patient care and clinical practice in comparison to existing agents: Daridorexant can be administered in diverse patient populations because of its tolerability and favorable safety profile. However, due to the lack of large scale studies that directly compare dual orexin receptor antagonists (DORAs), there is not enough data to recommend 1 DORA over another. Conclusions: Daridorexant is well tolerated and has demonstrated significant reductions in LPS and WASO in the treatment of insomnia in adult patients.

Automated summary

This article reviews the pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of daridorexant in patients with insomnia. Daridorexant demonstrates favorable tolerability and significant reductions in LPS and WASO in adult patients with insomnia.