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Benefit-Risk Assessment of Zaleplon in the Treatment of Insomnia

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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(ω1) receptor subtypes of the GABAA 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 efficacious in promoting sleep initiation, but less so in promoting sleep maintenance. The adverse effects associated with zaleplon have been shown to be more rapidly resolved and/or lesser in magnitude than those associated with benzodiazepines (including triazolam) and the longer acting non-benzodiazepine hypnotics (zolpidem and zopiclone). This improved risk profile includes: the effects of zaleplon on psychomotor and cognitive performance; tolerance, withdrawal and rebound; respiratory depression; sleep architecture; and other treatment-emergent adverse effects. The unique benefit-risk profile of this agent may be particularly suitable for certain patients with insomnia and provides yet another option in the management of this impairing condition.

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Acknowledgments

No sources of funding were used to assist in the preparation of this review. Dr Barbera has been involved in hypnotic studies for Sanofi-Synthelabo and Aventis. Dr Shapiro has acted as a consultant and carried out research for several companies that manufacture hypnotics, including Sanofi-Synthelabo, Aventis and Rhone-Poulanc.

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  1. Sleep Research Unit, University Health Network, TWH, 11th floor, Main Pavillion, 399 Bathurst Street, Toronto, M5T 258, Ontario, Canada

    Joseph Barbera & Colin Shapiro

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  1. Joseph Barbera
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  2. Colin Shapiro
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Correspondence to Joseph Barbera.

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Barbera, J., Shapiro, C. Benefit-Risk Assessment of Zaleplon in the Treatment of Insomnia. Drug-Safety 28, 301–318 (2005). https://doi.org/10.2165/00002018-200528040-00003

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