ABSTRACT
INTRODUCTION Many different agents are prescribed to treat insomnia. These agents represent at least 12 different medication classes. Among these classes are agents which mediate their therapeutic effect by binding to sites on the gamma-aminobutyric acid (GABA) type A receptor complex, thereby enhancing the inhibition that occurs when GABA binds to this receptor (1,2). These agents represent a set of chemically related compounds referred to as benzodiazepines and include triazolam, temazepam, flurazepam, diazepam, alprazolam, lorazepam, and oxazepam (2) (Table 1). The benzodiazepines can have a diverse set of effects via their modulation of GABAA receptors. These effects include sedation, anxiolysis, myorelaxation, antiseizure effects, and psychomotor impairment (2). There appears to be variation among the benzodiazepines in their profile of relative potency for these effects; however, all of them have some degree of sleep enhancement. However, only five of these agents are indicated for insomnia treatment by the U.S. Food and Drug Administration (FDA): triazolam, temazepam, flurazepam, estazolam, and quazepam (Table 1) (3).Agents that modulate GABAA receptors at the same binding sites as the benzodiazepines but that are unrelated chemically to these medications have been referred to as “nonbenzodiazepines” (3). Nonbenzodiazepines indicated for the treatment of insomnia in the United States include zolpidem, zolpidem CR, zaleplon, and eszopiclone. Together the benzodiazepines and nonbenzodiazepines have been referred to as “benzodiazepine receptor agonists” (BzRAs). While these agents are actually allosteric modulators and not agonists, because this is the most commonly used term for these medications, it will be adopted here as well (1). The BzRAs have dominated the pharmacologic management of insomnia for the last 50 years. They represent nearly all of the medications that have been approved by the FDA for the treatment of insomnia during this period. There is a substantial body of literature documenting their therapeutic effects in the treatment of insomnia. This chapter reviews this literature with the goal of providing an overview of their indications, the evidence for efficacy, and the data related to treatment outcome.
