Benefit-Risk Assessment of Zaleplon in the Treatment of Insomnia

Abstract

Insomnia is a heterogeneous, highly prevalent condition that is associated with a high level of psychiatric, physical, social and economic morbidity. The treatment of insomnia involves pharmacological and non-pharmacological interventions. The mainstay of pharmacological treatment of insomnia has been the benzodiazepines, the introduction of which represented a significant improvement over the barbiturates and chloral hydrate. Although benzodiazepines have been shown to be efficacious in treating insomnia, they have also been associated with a number of adverse effects including tolerance, dependence, withdrawal and abuse potential, impairment in daytime cognitive and psychomotor performance (including an increased risk of accidents and falls), adverse effects on respiration and the disruption of normal sleep architecture with reduction in both slow wave sleep and rapid eye movement. In the last decade, the treatment of insomnia has been supplemented by the introduction of a number of non-benzodiazepine hypnotics including zolpidem, zopiclone and, most recently, zaleplon. Zaleplon possesses a unique pharmacological profile, with an ultra-short half-life of about 1 hour, and selective binding to the BZ1(omega1) receptor subtypes of the GABA(A) receptor. This unique pharmacological profile predicts a number of pharmacodynamic properties that account for a unique benefit-risk profile. Consistent with these predictions, zaleplon has been shown in a number of studies to be efficac…