Zopiclone, the third generation hypnotic: a clinical overview

Effective and safe hypnotics exist especially since the introduction of benzodiazepines (BZD) which appeared to bring major advantages over barbiturates. Ideally a new hypnotic should induce and maintain sleep without producing residual effect during the day and should be devoid of abuse and dependence potential. Zopiclone is a new hypnotic belonging to the cyclopyrrolone chemical class. Its elimination half-life is 5 to 6 h, no accumulation exists upon repeated administration, and its pharmacokinetic profile is not substantially modified in elderly and renal failure patients. Placebo-controlled studies have shown that zopiclone 7.5 mg is an effective hypnotic, and that it can improve all sleep variables in insomniacs. Its effects on sleep stages differ from those observed with BZD hypnotics: REM sleep is substantially unaffected by zopiclone and slow wave sleep is either unaffected or increased. Objective and subjective measurements during the day after bedtime administration of zopiclone, showed lack of residual effects and no residual impairment of cognitive functions. Zopiclone discontinuation is not accompanied by rebound effect and relevant withdrawal symptoms. Specific "craving effect" studies in alcoholics did not show an abuse potential for zopiclone. Side-effects are represented mainly by bitter taste and dry mouth with a minimal incidence of CNS depressant effects. Studies on the effects of zopiclone on respiratory functions failed to show detrimental effects. Efficacy and safety data on zopiclone suggest that this new drug can represent a useful alternative to existing hypnotics.