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The efficacy of zolpidem, a non benzodiazepine hypnotic agent with a short elimination half life, was reviewed, analysing more than 50 international clinical trials published since 1986. The hypnotic activity of zolpidem has been explored in different patient populations including normal volunteers, general practice outpatients and psychiatric out- or in-patients with varying sleep disorders; both transient and chronic. Assessment methods used have included objective and subjective measures of hypnotic efficacy for different treatment durations, with results confirming that 10 mg is superior to placebo. Zolpidem was shown to be superior in most trials on sleep parameters such as total sleep time, sleep onset latency and nocturnal awakenings, but total REM sleep and REM latency were usually unmodified. Zolpidem maintained normal sleep physiology as demonstrated by the preservation of slow wave stages and no, or minimal, effects on sleep architecture after abrupt discontinuation. Consequently, 10 mg is the recommended dose for the short-term treatment of insomnia in the non-elderly; in elderly patients 5 mg has been shown to be effective at inducing sleep whilst giving an optimum safety profile.

The difficulty to recruit homogeneous samples of insomniacs requires alternative approaches for sleep studies. Acoustic perturbation in healthy volunteers made it possible to determine an experimental model of acute situational insomnia in order to investigate the effects of classic and novel hypnotic compounds. Unfortunately, the traditional scoring parameters of sleep are inadequate to provide reliable information for defining the neurophysiological bases of insomnia and for evaluating the efficacy of hypnotic drugs. Recent studies on the microstructure of sleep have permitted to identify a specific EEG feature, the cyclic alternating pattern (CAP), correlated with the subjective appreciation of sleep quality. Comparing placebo, zolpidem, zopiclone, lorazepam and triazolam, given at equivalent therapeutic doses in middle-aged healthy volunteer subjects under basal conditions and under acute situational insomnia, provided non-significant information when using classical sleep parameters whereas CAP rate (the percentage ratio of CAP time to non-REM sleep time) permitted to discriminate the basal nights from the perturbed nights and the drug nights from the placebo nights. These data have been confirmed in clinical studies using zolpidem versusplacebo in chronic insomniacs.