BEYOND BENZODIAZEPINES - ALTERNATIVE PHARMACOLOGICAL 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 inso mnia. Novel nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well as nonprescription products such as valerian an d melatonin, are reviewed in detail. DATA SOURCES: A MEDLINE search wa s performed to identify relevant clinical studies, case reports, abstr acts, and review articles published between April 1992 and December 19 97. Key search terms included insomnia, benzodiazepines, zolpidem, zop iclone, zaleplon, Cl 284,846, melatonin, and valerian. Additional refe rences 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 tri als and abstracts. Background information regarding insomnia, benzodia zepines, and other hypnotics was extracted from the most current Liter ature, including review articles and textbooks. CONCLUSIONS: New devel opments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzod iazepines. Although they may possess theoretical advantages over benzo diazepines based on their unique pharmacologic profiles, they offer fe w, if any, significant advantages in terms of adverse effects. Over-th e-counter agents such as valerian and melatonin may be useful in allev iating mild, short-term insomnia, but further clinical trials are requ ired to fully evaluate their safety and efficacy.