The Evolution and Development of Insomnia Pharmacotherapies

The National Institutes of Health (NIH) 2005 State of the Science Conference on the Manifestations and Management of Chronic Insomnia in Adults panel report concluded that insomnia is a problem, at least occasionally, for approximately 30% of adults in the general population, that insomnia is a chronic problem for about 10% of adults, and that in clinical settings the insomnia prevalence is roughly 50%.1 The report reinforced the view that insomnia should be appreciated as more than just a nighttime nuisance, but rather a condition that also affects daytime functioning, quality of life, and other mental and physical health outcomes.2 Insomnia sometimes is described as a contemporary problem resulting from modern-day societal stressors. However, it is hard to imagine that famine, warfare, pestilence, and other health concerns have not contributed to insomnia throughout the history of mankind. No doubt, processes of psychological conditioning also have perpetuated chronic insomnia throughout human history. People likely have sought relief with a wide assortment of substances. Fermented beverages have been available for millennia and alcohol remains a popular, though problematic, choice in the attempt to achieve improved sleep. Likewise, the sedative properties of opium were noted in ancient writings. With the Industrial Revolution came a variety of compounds that were packaged and marketed as sleep aids. While the effects of opium were known for thousands of years, it became a patent medicine product in the 1800s when it was combined with alcohol and sold as laudanum. Although an efficacious hypnotic, there were serious safety problems, including dependency and respiratory depression. Label prescribing guidelines included doses for infants and young children, and many deaths were associated with its use. Chloral hydrate, another abusable sedating medicine employed to induce sleep, became widely used beginning in the mid-19th century. Barbiturates were developed in the early 20th century and remained the primary prescribed hypnotic medications until the 1960s. Other past hypnotics included glutethimide, ethchlorvynol, paraldehyde and bromide preparations. All of these substances have had reasonable efficacy in promoting sleep, but there have been serious safety concerns with each medication. The evolution of insomnia treatment with pharmaceutical approaches in recent decades primarily has been manifest in major improvements in safety. This review will focus on the pharmacological characteristics and clinical value of the medications and related substances that currently are used with the intention of helping with difficulty falling asleep or remaining asleep. The efficacy of these compounds ranges from negligible to well established, and several have significant safety issues. Compounds recommended for insomnia include widely available unregulated substances and over-the-counter (OTC) medications, as well as prescription medicines that are used either off-label or with a US Food and Drug Administration (FDA) approved indication for the treatment of insomnia. Currently the only medications approved for the treatment of insomnia are benzodiazepine receptor agonist hypnotics and a selective melatonin receptor agonist.