Long-term use of dual orexin receptor antagonists for the treatment of insomnia: a systematic review and meta-analysis.

BACKGROUND: Insomnia is a prevalent disorder associated with impaired daytime functioning and reduced quality of life. Dual orexin receptor antagonists (DORAs) have shown favorable short-term efficacy and safety profiles. However, evidence regarding their long-term (≥ 6 months) effects remains limited. OBJECTIVE: To synthesize the available evidence on prolonged DORA use in adults with chronic insomnia. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trial. Adults with primary insomnia treated with DORAs (suvorexant, lemborexant, or daridorexant) approved by the United States Food and Drug Administration (FDA) for ≥ 6 months were included. The outcomes included patient-reported sleep parameters, adverse events, and treatment discontinuation. RESULTS: We included 6 randomized controlled trials comprising 3,546 participants. After 6 and 12 months, DORAs improved subjective sleep parameters of efficacy. Overall, DORAs showed adverse events similar to those of placebo at 6 months, but higher rates at 12 months. The overall rate of discontinuation due to adverse events did not differ significantly, although higher doses of certain DORAs increased the discontinuation rate at 6 months. CONCLUSION: In chronic insomnia, DORAs provide sustained improvements in key subjective sleep outcomes, with overall acceptable safety and tolerability profiles. Higher doses may be less well tolerated. Additional long-term randomized trials are needed to better define the efficacy and safety of DORAs in clinical practice.