A systematic review and network meta-analysis provided the most comprehensive data synthesis on pharmacological treatments for adults with insomnia. The study included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomized controlled trials (30 interventions and 44 089 participants) for the network meta-analysis. Benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo for acute treatment (standardized mean differences [SMD] range: 0·36–0·83, confidence in network meta-analysis [CINeMA estimates of certainty]: high to moderate). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27–0·71, moderate to very low). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (odds ratio [OR] 0·72, moderate; 0·70, moderate and 0·71, moderate, respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00, very low; zolpidem: 1·79, moderate); and zopiclone caused more dropouts than did eszopiclone (OR 1·82, low]), daridorexant (OR 3·45, low), and suvorexant (OR 3·13, low). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27–2·78, high to very low). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63, very low]; lemborexant: 0·41, very low) and eszopiclone was more effective than ramelteon (0.63, very low) and zolpidem (0·60, very low). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43, very low; zolpidem: 0·43, very low); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00, very low). In general, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. However, non-pharmacological treatments for insomnia are supported by high-quality evidence and recommended as first-line treatment by guidelines. Source: https://www.thelancet.com/
