Trends in the Pharmacologic Management of Insomnia

A variety of methods have been used to treat insomnia over the years. Alcohol, opium, and herbs were replaced by barbiturates early in the 20th century. In the 1960s, barbiturates were replaced with a safer class of medication, the benzodiazepines. Later, the selective benzodiazepine receptor agonists (BZRAs), agents that work through the benzodiazepine receptor but are not chemically benzodiazepines, were developed. These medications have proved to be safer, less toxic, and just as effective without the heightened risk of dependence compared with their predecessors. Several over-the-counter medications, including antihistamines, herbal supplements, valerian, melatonin, and l-tryptophan, are popular sleep aids, but little evidence supports their use for insomnia. Despite the lack of U.S. Food and Drug Administration (FDA) approval for insomnia, the risk of adverse events, and limited efficacy, antidepressants remain popular treatments for sleep disorders. Recent FDA approvals of 2 longer acting selective BZRAs have been unique in their lack of limitation to short-term usage as well as their indication for sleep maintenance. In late 2005, the melatonin receptor agonist ramelteon was approved for sleep initiation and is likewise not restricted to short-term use. New compounds under development include indiplon, another selective BZRA, and gaboxadol, a selective extrasynaptic γ-aminobutyric acid-A agonist. Additional melatonin receptor agonists and medications that work through the serotonin system are under development. Physician education is an important component to ensuring that patients receive safe and adequate treatment for their insomnia.