Long-term dual orexin receptor antagonists maintain sleep improvements in chronic insomnia

This systematic review and meta-analysis pooled data from 6 randomized controlled trials with 3,546 participants taking DORAs (suvorexant, lemborexant, or daridorexant) for at least 6 months to assess long-term effectiveness and safety. After both 6 and 12 months of use, DORAs were associated with sustained improvements in subjective sleep measures—how people report their sleep quality and duration. Safety findings were mixed: at 6 months, adverse event rates were similar to placebo, but at 12 months, DORAs showed higher adverse event rates than placebo. Importantly, discontinuation due to adverse events did not differ significantly overall between DORA and placebo groups, though higher doses of some DORAs were linked to increased discontinuation at 6 months, suggesting dose selection matters for tolerability.

The meta-analysis found that improvements in subjective sleep quality—the primary outcome—remained consistent from 6 to 12 months, indicating DORAs do not lose efficacy with continued use in this timeframe. However, the rise in adverse event rates at 12 months deserves attention: while the authors note these rates were still manageable and discontinuation overall remained comparable to placebo, this trend suggests potential cumulative effects or emerging tolerability concerns at longer durations. Subgroup findings showed that higher doses of certain DORAs (notably at the 6-month mark) were associated with more discontinuations, implying that lower-to-moderate dosing may offer a better risk-benefit balance. The authors explicitly note that longer-term trials beyond 12 months remain scarce, so the safety and efficacy landscape beyond one year of continuous use is still poorly defined. This is particularly relevant for patients considering DORAs as maintenance therapy for chronic insomnia.