Journal
SLEEP MEDICINE REVIEWS
Volume 68, Issue -, Pages -Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.smrv.2023.101746
Keywords
Insomnia; Pharmacological treatments; Network meta-analysis; Objective sleep characteristics
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Insomnia is a common and burdensome disorder in adults. We compared and ranked the efficacy and tolerability of insomnia medication. 69 studies involving 17,319 patients were analyzed, and we found that orexin receptor antagonists (ORAs) were more effective and tolerable than benzodiazepine-like drugs (Z-drugs) and melatonin receptor agonists (MRAs) for insomnia treatment. The findings provide guidance for clinicians in choosing appropriate medications for insomnia symptoms.
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and toler-ability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.(c) 2023 Elsevier Ltd. All rights reserved.
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