The Efficacy and Safety of Dual Orexin Receptor Antagonists in Primary Insomnia: A Systematic Review and Network Meta-Analysis.

The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures.