A model-based meta-analysis (MBMA) of randomized, placebo-controlled trials of several insomnia medications showed that eszopiclone had the highest efficacy and was associated with the lowest dropout rate, according to findings published in Sleep Medicine.

Insomnia, characterized by disrupted aspects sleep latency, maintenance, or quality, is often treated with pharmacotherapies, such as benzodiazepines, tricyclic antidepressants, melatonin receptor agonists, and orexin receptor antagonists. While insomnia medication efficacy has been studied in meta-analyses, this efficacy has largely been focused on study endpoints rather than time-course responses.

In this study, researchers used MBMA to study the time-course efficacy of a range of drugs on 3 sleep parameters: time course of sleep latency, wake after sleep onset, and total sleep time. The study included placebo-controlled randomized trials in adults with insomnia disorder not caused by physical or psychiatric conditions, medication use, or substance abuse. The medications analyzed included flurazepam, quazepam, temazepam, triazolam, eszopiclone, zaleplon, zolpidem, extended-release zolpidem, suvorexant, ramelteon, and doxepin.

Sleep parameters were recorded by either sleep diaries or questionnaires as a subjective measure or polysomnography as an objective measure. Model-based statistical analysis involved 2 important parameters: theoretical maximal efficacy (Emax)and time required to achieve half the maximal efficacy (ET50).


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The researchers used 43 studies involving 44 trials with a total of 14,535 patients (mean age, 52.5±13.7 years; 32.6% men) to analyze sleep parameters at 4 weeks. All insomnia drugs improved the 3 sleep parameters when compared to placebo, with the exception of ramelteon, which was comparable with placebo. There was no significant time-response effect in terms of relative efficacy of the 11 drugs investigated, with the onset of action being fast. However, placebo response was “a major contributor to drug efficacy,” accounting for “about 60% of the absolute found drug efficacy.”

Eszopiclone was the most effective drug for reducing sleep latency (median: -31.2, 95% CI, -35.4 to -26.9) and increasing total sleep time (-63.4, 95% CI, -54.2 to -72.5), with a respective change of 16 and 34 minutes vs placebo. Furthermore, eszopiclone was also effective at increasing sleep quality, with a change in sleep quality score of -1.6 (95%CI, -2.0 to -1.2) compared to placebo at -0.5 (95% CI, 0.7 to -0.2), and it had the lowest dropout rate (2.2%), whereas doxepin had the highest (16.7%).

Suvorexant was the most effective at reducing wake after sleep onset, with a change of 34 minutes compared to placebo (-41.2, 95% CI, -46.1 to -36.3). The researchers found no significant time-response effect of the relative efficacy of the selected insomnia drugs.

Study limitations included a lack of data on potential confounding factors and the exclusion of patients with comorbidities, which commonly occur with insomnia, thus limiting the generalizability of the results.

“Each drug has its own characteristics in the treatment of insomnia, and this needs to be taken into consideration to meet individual clinical needs,” the researchers concluded.

Reference

Zheng X, He Y, Yin F, et al. Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy [published online ahead of print, 2020 Apr 1]. Sleep Med. 2020;72:41-49.