Zolpidem is the most widely used prescription drug for insomnia and one of the most commonly used drugs in the United States. Treatment of insomnia, which has important effects on patients’ quality of life, may also have larger public health benefits. In its 2006 report, the Institute of Medicine (IOM) Committee on Sleep Medicine and Research concluded that sleep deprivation and sleep disorders represent an unaddressed public health problem that has substantial health consequences and leads to high health care costs.1 The IOM noted that one of every five serious injuries from driving accidents can be attributed to driver sleepiness. Numerous sleep drugs are available for treating insomnia and are also used to reduce next-day somnolence. But it is widely recognized that these drugs themselves can sometimes contribute to next-day somnolence, depending on such factors as drug dose, dosage form, and individual patient characteristics.
Zolpidem was initially approved, in 1992, in an immediate-release formulation for insomnia characterized by difficulty in falling asleep. At the time of its approval, there was concern regarding morning impairment, even after a 7-to-8-hour period of sleep, particularly with regard to activities requiring full alertness, such as driving a motor vehicle. There was also some recognition that people’s risk of impairment could vary, and the drug label advised that “the dose of Zolpidem should be individualized.” Although the recommended adult dose was 10 mg, the recommended dose for the elderly (who had higher levels of the drug in their blood the next morning) and for patients with hepatic impairment (who metabolized the drug more slowly) was 5 mg. Individual differences became more apparent as new dosage forms of zolpidem were developed to address sleep maintenance and middle-of-the-night waking.
Manufacturers of zolpidem-containing products must now make dosage recommendations that differ for women and men, to decrease the likelihood that women will have blood levels of the drug after they wake up that will impair their driving ability. Accordingly, the recommended dose of zolpidem for women has been reduced from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for modified-release products.
The FDA has also pointed out that the risk of impairment with modified-release formulations of zolpidem is greater than the risk with immediate-release formulations. Accordingly, the agency announced in May 2013 that patients who take modified-release formulations, either 6.25 mg or 12.5 mg, even if they then sleep for the required 8-hour period, should refrain, for the day subsequent to using the drug, from driving or engaging in any activity that requires full alertness. This recommendation reflects not only the higher zolpidem content in the modified-release formulation but also the ability of the modified-release design to prolong the period of drug exposure. A variety of new data have shown that people affected by impairment after taking zolpidem frequently do not recognize their impaired state; patient self-perception is not an adequate gauge for impairment.