Hypnotic drugs are often prescribed in primary care for insomnia. Despite a reduction in prescribing of benzodiazepine hypnotics in the past decade, hypnotic use and costs remain high because of the introduction and increase in use of ‘Z’ drugs, a group of non-benzodiazepine hypnotic drugs (including eszopiclone, zaleplon and zolpidem), which act on the GABA (γ-aminobutyric acid) receptor and are used in the treatment of insomnia. Z drugs are now the most commonly prescribed hypnotic agents worldwide, but are not without risks. 

These include adverse cognitive effects (such as memory loss), psychomotor effects (such as falls, fractures, road traffic crashes), daytime fatigue, tolerance, addiction and excess mortality with no significant difference from benzodiazepines. 

These established risks need to be weighed against the benefits. Previous meta-analyses of clinical trials of Z drugs have been prone to publication bias, with a tendency to emphasise positive results. One way of reducing this problem of publication bias is to analyse the effect of drugs that have been approved by governmental agencies with data derived from regulatory submissions

This study,1 with authors based in the US and UK, is a systematic review and meta-analysis of randomised double blind parallel placebo-controlled trials of currently approved Z drugs (eszopiclone, zaleplon and zolpidem).

Thirteen studies containing 65 separate drug-placebo comparisons by type of outcome, type of drug and dose were included. Studies included 4,378 participants from different countries and varying drug doses, lengths of treatment and study years. Z drugs showed significant, albeit small, improvements (reductions) in the primary outcomes: polysomnographic sleep latency (weighted standardised mean difference, 95% confidence interval −0.57 to −0.16) and subjective sleep latency (−0.33, −0.62 to −0.04) compared with placebo. 

Perhaps the most interesting finding in the study is that there was a significant placebo response in virtually all the trials. For example, sleep latency (time to fall asleep) was reduced by 20 minutes with placebo and 40 minutes with the active drug and total sleep time increased by 35 minutes with placebo and 50 minutes with the active drug. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produced a reasonably large clinical response.