Rosner S, Englbrecht C, Wehrle R, et al. Eszopiclone for insomnia. Cochrane Database Syst Rev. 2018 Oct 10;10:CD010703. doi: 10.1002/14651858.CD010703.pub2. (Systematic review)

BACKGROUND: Insomnia is a major public health issue affecting between 6% to 10% of the adult population in Western countries. Eszopiclone is a hypnotic drug belonging to a newer group of hypnotic agents, known as new generation hypnotics, which was marketed as being just as effective as benzodiazepines for this condition, while being safer and having a lower risk for abuse and dependence. It is the aim of the review to integrate evidence from randomised controlled trials and to draw conclusions on eszopiclone's efficacy and safety profile, while taking methodological features and bias risks into consideration.

OBJECTIVES: To assess the efficacy and safety of eszopiclone for the treatment of insomnia compared to placebo or active control.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, Embase, PsycINFO, PSYNDEX and registry databases (WHO trials portal, with results incorporated from searches to 10 February 2016. To identify trials not registered in electronic databases, we contacted key informants and searched reference lists of identified studies. We ran an update search (21 February 2018) and have placed studies of interest in awaiting classification/ongoing studies. These will be incorporated into the next version of the review, as appropriate.

SELECTION CRITERIA: Parallel group randomised controlled trials (RCTs) comparing eszopiclone with either placebo or active control were included in the review. Participants were adults with insomnia, as diagnosed with a standardised diagnostic system, including primary insomnia and comorbid insomnia.

DATA COLLECTION AND ANALYSIS: Two authors independently extracted outcome data; one reviewer assessed trial quality and the second author cross-checked it.

MAIN RESULTS: A total of 14 RCTs, with 4732 participants, were included in this review covering short-term (= 4 weeks; 6 studies), medium-term (> 4 weeks = 6 months; 6 studies) and long-term treatment (> 6 months; 2 studies) with eszopiclone. Most RCTs included in the review included participants aged between 18 and 64 years, three RCTs only included elderly participants (64 to 85 years) and one RCT included participants with a broader age range (35 to 85 years). Seven studies considered primary insomnia; the remaining studies considered secondary insomnia comorbid with depression (2), generalised anxiety (1), back pain (1), Parkinson's disease (1), rheumatoid arthritis (1) and menopausal transition (1).Meta-analytic integrations of participant-reported data on sleep efficacy outcomes demonstrated better results for eszopiclone compared to placebo: a 12-minute decrease of sleep onset latency (mean difference (MD) -11.94 min, 95% confidence interval (CI) -16.03 to -7.86; 9 studies, 2890 participants, moderate quality evidence), a 17-minute decrease of wake time after sleep onset (MD -17.02 min, 95% CI -24.89 to -9.15; 8 studies, 2295 participants, moderate quality evidence) and a 28-minute increase of total sleep time (MD 27.70 min, 95% CI 20.30 to 35.09; 10 studies, 2965 participants, moderate quality evidence). There were no significant changes from baseline to the first three nights after drug discontinuation for sleep onset latency (MD 17.00 min, 95% CI -4.29 to 38.29; 1 study, 291 participants, low quality evidence) and wake time after sleep onset (MD -6.71 min, 95% CI -21.25 to 7.83; 1 study, 291 participants, low quality evidence). Adverse events during treatment that were documented more frequently under eszopiclone compared to placebo included unpleasant taste (risk difference (RD) 0.18, 95% CI 0.14 to 0.21; 9 studies, 3787 participants), dry mouth (RD 0.04, 95% CI 0.02 to 0.06; 6 studies, 2802 participants), somnolence (RD 0.04, 95% CI 0.02 to 0.06; 8 studies, 3532 participants) and dizziness (RD 0.03, 95% CI 0.01 to 0.05; 7 studies, 2933 participants). According to the GRADE criteria, evidence was rated as being of moderate quality for sleep efficacy outcomes and adverse events and of low quality for rebound effects and next-day functioning.

AUTHORS' CONCLUSIONS: Eszopiclone appears to be an efficient drug with moderate effects on sleep onset and maintenance. There was no or little evidence of harm if taken as recommended. However, as certain patient subgroups were underrepresented in RCTs included in the review, findings might not have displayed the entire spectrum of possible adverse events. Further, increased caution is required in elderly individuals with cognitive and motor impairments and individuals who are at increased risk of using eszopiclone in a non-recommended way.

Discipline Area Score
Physician 6 / 7
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Comments from MORE raters

Physician rater

Eszopiclone seems to be an efficient and safe hypnotic drug and is well tolerated according to this Cochrane meta-analysis. The main objection is that aged people are unrepresented in many of the clinical trials, and this limits the external validity of the meta-analysis.

Physician rater

I found this article dealing with insomnia useful. Insomnia is a major public health issue in Western countries. In particular, many prospective studies suggested that postmenopausal women with insomnia had higher BMI, higher proportions of use of sleep aids, higher proportion of diabetes, CVD, and/or cancer and higher levels of depression. This review pointed to eszopiclone (lunesta), which belongs to non-benzodiazepine hypnotics, as an efficient drug with moderate effects on sleep onset and maintenance. Further studies are required in elderly individuals with cognitive and motor impairments and individuals who are at increased risk for using eszopiclone in a non-recommended way. Further research regarding insomnia, either primary or secondary, should to be continued. Because of the association of insomnia with increased mortality, all factors disrupting sleep should be adequately addressed with appropriate instruments and therapeutic strategies.

Physician rater

Helpful that there was not much evidence of harm if used short term and for appropriate indications.
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