Beyond benzodiazepines: Alternative pharmacologic agents for the treatment of insomnia

OBJECTIVE: To review the epidemiology, etiology, and classification of insomnia and provide an overview of the pharmacologic therapy of insomnia. Novel nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well as nonprescription products such as valerian and melatonin, are reviewed in detail. DATA SOURCES: A MEDLINE search was performed to identify relevant clinical studies, case reports, abstracts, and review articles published between April 1992 and December 1997. Key search terms included insomnia, benzodiazepines, zolpidem, zopiclone, zaleplon, CI 284,846, melatonin, and valerian. Additional references were obtained from the lists of review articles and textbooks. DATA EXTRACTION AND SYNTHESIS: Data concerning the safety and efficacy of the hypnotic agents were extracted from all available clinical trials and abstracts. Background information regarding insomnia, benzodiazepines, and other hypnotics was extracted from the most current literature, including review articles and textbooks. CONCLUSIONS: New developments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzodiazepines. Although they may possess theoretical advantages over benzodiazepines based on their unique pharmacologic profiles, they offer few, if any, significant advantages in terms of adverse effects. Over-the-counter agents such as valerian and melatonin may be useful in alleviating mild, short-term insomnia, but further clinical trials are required to fully evaluate their safety and efficacy.