Zolpidem and driving impairment--identifying persons at risk.

n engl j med 369;8 nejm.org august 22, 2013 689 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. The treatment of insomnia may focus on two distinct problems: falling asleep and remaining asleep; drugs that treat insomnia may be directed at one or both of these problems. For patients whose main problem is falling asleep, shorter-acting drugs can be effective without conferring a risk of sedation the following morning. When the problem is staying asleep during the night (sleep maintenance), longer-acting drugs — drugs with longer halflives or controlled-release formulations — are generally used. Some patients can also take a very small dose of a sleep drug (e.g., zolpidem is available at a dose of 1.75 to 3.5 mg) or a very short-acting drug (e.g., zaleplon) if they wake up in the middle of the night and have difficulty falling back asleep. Zolpidem was initially approved, in 1992, in an immediaterelease formulation (Ambien) 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 Ambien 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 middleof-the-night waking. In 2005, a modified-release forZolpidem and Driving Impairment — Identifying Persons at Risk