Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis

ABSTRACT

Background

Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.

Methods

An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms ‘Daridorexant,’ ‘RCT,’ ‘Insomnia’ trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.

Results

Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I² = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I² = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I² = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I² = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.

Conclusion

Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.

Prospero

The registration number is CRD42022335233.

Clinical trial registration

www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

KEYWORDS:

• Daridorexant
• insomnia
• orexin
• dual orexin receptor antagonist
• adverse events
• Serious adverse events

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Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2243217

Reviewer disclosures

One reviewer serves as a consultant to Idorsia (manufacturer of daridorexant) and to Eisai (manufacturer of a competitor). The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contribution statement

All authors have substantially contributed to the conception, design synthesis of this manuscript, involved in writing the review article or revised it for intellectual content and have agreed to the final version of the manuscript. Siddhartha Dutta, Shubha Singhal, and Rima Shah made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation. They have also drafted or written, or substantially revised or critically reviewed the article. Jaykaran Charan- data analysis and interpretation, Grading of evidence by GRADEPro GDT tool, substantially revised or critically reviewed the article. Sameer Dhingra and Mainul Haque- interpretation, substantially revised or critically reviewed the article.

Additional information

Funding

This paper was not funded.