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Influence of Pharmacokinetic Profiles on Safety and Efficacy of Hypnotic Medications

Milton K. Erman, MD

Published: November 15, 2006

Article Abstract

Occasional trouble sleeping is part of the human condition, but persistent insomnia is not. Pharmacotherapy is the most common treatment for insomnia. Benzodiazepines, nonbenzodiazepine hypnotics, and melatonin receptor agonists are among the most studied compounds for the treatment of insomnia. These compounds differ in their sites of action in the brain, their half-lives, and their durations of action. These differences allow clinicians to make therapeutic choices based on the specific sleep needs of individual patients. For example, medications with a rapid onset of action and a short half-life are likely to be effective for sleep initiation but unlikely to improve sleep maintenance. A compound with a longer half-life would be expected to sustain sleep on a more extended basis but could lead to residual sedation. A (theoretically) ideal compound for promoting and sustaining sleep over a desired period of time would be one with an immediate onset of action, a sustained effect for the desired duration of effect, and rapid reduction in effect after this period of time. The benzodiazepines tend to have longer half-lives than the nonbenzodiazepines but carry a greater risk for residual sedation. The melatonin receptor agonist ramelteon has a short half-life and is not indicated for sleep maintenance.

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