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  • Title: Treatment options for insomnia--pharmacodynamics of zolpidem extended-release to benefit next-day performance.
    Author: Bogan RK.
    Journal: Postgrad Med; 2008 Sep; 120(3):161-71. PubMed ID: 18824834.
    Abstract:
    BACKGROUND: Insomnia can manifest as difficulty in falling asleep, in maintaining sleep throughout the night, or waking up too early, with symptoms often unpredictably changing over time. Pharmacologic options for insomnia treatment include prescription hypnotics, such as gamma-amino butyric acid-receptor agonists, sedating antidepressants, over-the-counter antihistamines, melatonin-receptor agonists, and alternative therapies. A concern with insomnia medications is the risk of next-day residual effects, which can impair memory and ability to perform certain tasks, such as driving, and may increase the risk of accidents and falls, especially in the elderly. OBJECTIVES: To describe the impact of current insomnia treatments on next-day performance. RESULTS: The longer-acting benzodiazepines are associated with next-day "hangover" effects and, as a result, have been largely replaced by agents in the nonbenzodiazepine class, which typically have shorter half-lives. The hypnotic, sedative activities of these classes of drugs depend on variations in binding characteristics to the alpha1 subunit of the gamma-amino butyric acidA-receptor, which inhibits neuronal activity in broad areas of the brain and is found in areas of the brain responsible for sleep/wakefulness and sedation. However, nonbenzodiazepines with a rapid onset of action and short half-life have shown limited efficacy for maintaining sleep throughout the night. These properties have contributed to the development of modified-release formulations. Zolpidem extended-release is a bilayer tablet that retains the fast onset of action of its parent compound zolpidem while extending the duration of hypnotic activity, owing to a slower-release portion of the tablet. CONCLUSIONS: Based on clinical evidence, the risk of residual next-day effects of zolpidem extended-release is limited, mainly due to the similarly short half-life in its extended-release formulation.
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