1. Eszopiclone and Lemborexant were more efficacious for acute and long-term insomnia compared to placebo, but were associated with more drop-outs due to adverse events compared to placebo.
2. Intermediate-acting benzodiazepines showed a more acceptable tolerability compared to short-acting and long-acting benzodiazepines.
Evidence Rating Level: 1 (Excellent)
Study overview: Insomnia is a common sleep disorder that affects 12-20% of adults worldwide. Although first-line therapy for insomnia involves conservative treatment, studies show that pharmacological measures can help improve insomnia. However, little is known about the comparative efficacy of the different pharmacological options available. This systematic review and meta-analysis aimed to study the safety and efficacy of pharmacotherapy for acute and chronic treatment of insomnia in adults. Primary outcomes were safety (≥1 adverse event), efficacy (patient-reported sleep quality), and discontinuation of treatment due to any etiology, while key secondary outcomes were the latency period of falling asleep, total sleep time, and number of awakenings. According to research results, pharmacological treatment of insomnia was associated with greater efficacy but more side effects than placebo in both acute and long-term insomnia. In particular, eszopiclone and lemborexant were found to be more effective for both acute and long-term treatment of insomnia compared to placebo and other pharmacological interventions. Melatonergic drugs showed no apparent benefit over placebo. A limitation of this study is that it did not contain trazodone, one of the most common clinically used drugs for insomnia.
Click to read the study in The Lancet
Relevant literature: effect of digital cognitive behavioral therapy for insomnia on health, psychological well-being and sleep-related quality of life: a randomized clinical trial
in-depth [systematic review and meta-analysis]: This systematic review and meta-analysis includes RCTs from Cochrane, MEDLINE, PubMed, Embase, and PsycINFO. Included were studies using pharmacotherapy as first-line treatment for insomnia in patients ≥ 18 years of age, from database initiation to November 25, 2021. A total of 170 RCTs and 154 double-blind RCTs were included in the final systematic review and meta-analysis, respectively. With regard to the primary outcome of safety, more adverse events were reported in the zopiclone (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.28-3.13) and zolpidem (OR 1.79, 95% CI 1.25-2.50) versus placebo. In addition, patients assigned to placebo, doxepin, seltorexant, and zaleplon reported fewer side effects than those who received benzodiazepines, eszopiclone, zolpidem, and zopiclone. Eszopiclone and lemborexant were shown to be effective for acute insomnia (standardized mean difference [SMD] range 0.36-0.83) as well as chronic insomnia (eszopiclone: SMD 0.63 [0.36-0.90]; lemborexant: SMD 0.41 [0.04-0.78]) compared to placebo. However, eszopiclone was associated with more nausea and dizziness, while lemborexant was more likely to cause headaches than placebo. Eszopiclone (OR 0.43, 95% CI 0.20-0.93) and zolpidem (OR 0.43, 95% CI 0.19-0.95) also had a lower rate of all-cause discontinuations than ramelteon; for zolpidem the rate was higher than for placebo (OR 2.00, 95% CI 1.11-3.70). Overall, the findings of this study suggest that while pharmacologic treatment may have short-term benefits, long-term safety and efficacy remain unclear.
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