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Eszopiclone and lemborexant show favourable profile for management of insomnia

A network meta-analysis has suggested that both eszopiclone and lemborexant have the most favourable profile for the management of insomnia

Eszopiclone and lemborexant have the best profile with respect to efficacy, acceptability and tolerability in the management of insomnia although neither drug is ideal according to the findings of a network meta-analysis by an international research team.

Insomnia can be defined as a difficulty in getting to sleep, maintaining sleep, early wakening, or non-restorative sleep. Studies on the prevalence of insomnia in the general population indicate that one third of adults in Western countries experience difficulty with sleep initiation or maintenance at least once a week. Guidelines on the management of insomnia generally advocate the use of cognitive behavioural therapy as the first-line treatment for chronic insomnia in adults and a pharmacological intervention if cognitive behavioural therapy is not sufficiently effective or unavailable. Nevertheless, to date, there is a lack of comparative data for the different pharmacological interventions and this was the basis for the present systematic review and network meta-analysis designed to help inform clinician’s decision-making process in the management of acute and long-term insomnia. The authors searched for studies that compared different treatments or placebo in adults with insomnia and focused on randomised, controlled trials. Outcomes assessed included efficacy (based on self-reported sleep satisfaction or quality) and all-cause discontinuation.

Eszopiclone and insomnia outcomes

A total of 170 trials with 36 interventions and 47,950 participants were included. Among the 160 trials providing demographic data, the mean age of participants was 51.7 years (62.8% female) with a mean sample size per study of 265. The median duration of acute treatment was 2 weeks and 25 weeks for long-term studies.

For the efficacy analysis, acute treatment with eszopiclone, lemborexant and benzodiazepines were all more effective than placebo (standardised mean difference, SMD range 0.36 – 0.83). For longer term management, eszopiclone was more effective than placebo (SMD = 0.63, 95% CI 0.36 – 0.90) as was lemborexant (SMD = 0.41).

In terms of all-cause discontinuation, compared to ramelteon, eszopiclone had fewer event (odds ratio, OR = 0.43, 95% CI 0.20 – 0.93).

Discussing their findings, the authors noted that both eszopiclone and lemborexant had the best profile with respect to efficacy, acceptability and tolerability. However, neither drug was considered to be ideal because eszopiclone had the potential to cause substantial adverse events and the safety data for lemborexant was as inconclusive. A further limitation with the analysis was that while only 48.3% of included trials were rated as being of low risk of bias, in 19.4% of trials the risk was unclear and nearly a third (32.4%) were deemed at a high risk.

The authors were even more caution in their conclusion, suggesting that all statements comparing the merits of each drug should be tempered by the potential limitations of the available evidence, the patient characteristics and any uncertainties that may arise based on the dose and treatment setting.

De Crescenzo F et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis Lancet 2022

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