Zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist), zaleplon (Sonata), and eszopiclone (Lunesta) have long been known to potentially cause abnormal thinking and behavioral changes in adults who take these drugs to treat insomnia. Among these changes are decreased inhibition, bizarre behavior, agitation, depersonalization, and visual and auditory hallucinations. The drugs are also known to induce complex behaviors while the patient is still asleep, including sleepwalking, driving, preparing and eating food, making phone calls, and having sex. The patient generally has no memory of these actions. In an attempt to highlight that these behavioral changes can cause potentially fatal adverse effects, the Food and Drug Administration (FDA) has now added a black box warning to the drugs' labeling based on its review of 66 cases reported to the FDA Adverse Event Reporting System and the medical literature from December 16, 1992, to March 13, 2018. The FDA has also added a contraindication that patients with a history of complex sleep behaviors when taking zolpidem, zaleplon, or eszopiclone should not be prescribed these drugs. These labeling changes follow previous changes in 2013 and 2014 warning of next-day impairment and the need for lower recommended doses with zolpidem and eszopiclone.

Of the 66 case reports reviewed, the FDA identified 46 cases of nonfatal injuries and 20 cases of fatal injuries after use of these sedative-hypnotic drugs. Among these were falls with serious injuries, fatal falls, fatal motor vehicle accidents, self-injury, and suicidal attempts and suicides. Most case reports described patients taking zolpidem, the most commonly prescribed sedative-hypnotic. National prescription audit data from 2018 show that 5.1 million patients received a zolpidem prescription, 600,000 received an eszopiclone prescription, and 200,000 received a zaleplon prescription. The FDA notes that although the complex sleep behaviors caused by sedative-hypnotic drugs are not common, they can occur even when the lowest recommended dose is used, even after taking the very first dose of the drug, and even when the patient hasn't combined the drug with alcohol or other central nervous system depressants. The exact mechanism by which these drugs induce complex sleep behaviors is unknown.

NPs should not prescribe any of these drugs to patients who have a history of complex sleep behaviors after taking antiinsomnia drugs. When prescribing drugs to treat insomnia, the lowest approved dose should be given first. Nurses and NPs should teach patients about the risks of abnormal thinking, behavioral changes, and performing complex tasks while asleep. Patients should be instructed to stop using the drug if they experience any of these adverse effects, even if no harm came to them. Patients should be assessed carefully for mood changes. Nurses and other health care providers should report any drug-related adverse effects to the FDA's MedWatch program at http://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-repo.

To read the FDA Drug Safety Communication on the risk of serious injuries from insomnia medications, see http://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-ris.