What’s New in the Patient Safety World

May 2012

Safety of Hypnotic Drugs



Those who work in hospital or long-term care settings are familiar with many of the safety issues related to sedative/hypnotic drugs. They frequently are contributing factors to patient falls, delirium, and opioid-related respiratory depression. Sometimes we’ll see withdrawal syndromes in patients who have been receiving such drugs chronically. They may also play a role in predisposing some patients to aspiration. And they are a frequent contributor to events occurring in patients with sleep apnea. They appear on Beers’ List or other lists of drugs potentially contraindicated in the elderly. Some facilities have made concerted efforts to avoid use of sedative/hypnotics (see our August 2009 What’s New in the Patient Safety World column “Bold Experiment: Hospitals Saying No to Sleep Meds”). And we actively discourage including checkboxes for sleep meds on standardized order sets, whether they are paper-based or electronic (see our March 23, 2010 Patient Safety Tip of the Week “ISMP Guidelines for Standard Order Sets”).


But for the most part we have been paying attention to the adverse effects in a very narrow timeframe. And, other than hearing anecdotal stories about someone doing bizarre things at night and having no recall while on sleep meds, we haven’t paid as much attention to the long-term adverse effects of such drugs. But that seems to be changing.


A series of papers using data from a large integrated health system has documented an association between hypnotic drugs and mortality. The first paper (Kripke 2012) compared mortality rates in patients prescribed any hypnotics compared to a matched cohort that was not prescribed such drugs. Even after adjustment for potential confounding factors they found the risk for death was about 4.5 times higher in those who had been prescribed hypnotics. This applied to all hypnotics, including new agents that have long been felt to be “safer” than the older hypnotics. It also applied to all age groups and the hazard ratio was highest in the 18-55 year old age group. They did find a dose-response relationship where the risk increased with increasing numbers of sleep pills taken. However, even for the group taking 1-18 doses per year the hazard ratio for death was 3.60. For those taking over 132 doses per year, the hazard ratio was 5.32.  Patients in the latter category also had an association with an increased incidence of new cancer. The causes of death were not known but the authors speculate about multiple potential mechanisms by which hypnotic drugs might increase the risk of death.


A second paper by the same group and same database, presented in abstract form at the American Heart Association annual scientific sessions, found that the risk of death was even higher in the subset of patients having obesity (Langer 2012). Those in the highest tertile of sleep med use had a risk of death 9.3 times higher than those not taking sleep meds. Even those taking only 1-18 doses a year had a risk of death 8 times higher than similar patients not prescribed any sleep meds. And in this group men were about twice as likely as women to die. The authors speculate about the role of sleep apnea and its interaction with the sleep meds in this population.


While these two studies have uncovered an association between mortality and use of hypnotics, they do not confirm a cause-effect relationship. Nevertheless, the association is significant and should make us all think twice before prescribing hypnotics to anyone. There are multiple non-pharmacologic approaches that should be considered before you would use pharmacologic interventions for insomnia.


Be especially wary of using these drugs even temporarily in the hospital. It is amazing how often drugs begun in the hospital end up being continued indefinitely after the patient is discharged (see our March 2011 What’s New in the Patient Safety World column “Inappropriate Medications Often Start in the ICU”).



In our August 2009 What’s New in the Patient Safety World column “Bold Experiment: Hospitals Saying No to Sleep Meds” we noted Doylestown Hospital had already implemented a significant noise reduction program and were trying to make the inpatient environment conducive to sleep by lowering the lights, closing doors, allowing masks or earplugs, using more private rooms, and allowing personal stereos to be used. Hospital noise levels are unacceptably high and can lead to significant sleep loss for patients (Yoder 2012).


But the new studies suggesting a link between sedative/hypnotic drugs and mortality tell us we need to be doing much more on the outpatient side to reduce use of such drugs. You do, of course, need to consider the possibility of psychiatric conditions (particularly depression and anxiety) as causes for chronic insomnia. But in most cases you need to help patients adopt practices that promote good nocturnal sleep. That includes things like counseling them about eating and drinking habits in relation to time of day (eg. avoiding caffeinated beverages at night or avoiding large volumes of fluid that will lead to awakening to void). And you need to make sure that noise and light levels are not barriers to sleep and that the ambient temperature is conducive to sleep. Similarly, activities earlier in the day may be important. Getting some exercise, particularly outdoors, may benefit sleep as well as overall health. Attention to patterns of any naps may also identify why a patient has trouble sleeping at night.


Given the time pressures of outpatient medicine, it’s all too easy to simply write a prescription for a sleep med for your patient. But you’re probably not doing them any favors. The new studies suggest even the occasional use of sleep meds may be harmful. If you don’t have your own program for helping patients adopt non-pharmacological measures to improve their sleep, consider referring them to a sleep medicine specialist. Those specialists do a lot more than treat obstructive sleep apnea. They do comprehensive evaluations of a patient’s sleep and waking patterns and habits and first promote good sleep hygiene habits when approaching the patient with chronic insomnia.






Kripke DF, Langer RD, Kline LE. Hypnotics' association with mortality or cancer: a matched cohort study. BMJ Open 2012; 2: e000850 doi:10.1136/bmjopen-2012-000850

Published 27 February 2012




Langer RD, Kripke DF, Kline LE. Abstract 052: Short-acting Hypnotic Drugs Increase Mortality and Obese Patients are Particularly Vulnerable. Circulation. 2012; 125: A052




Yoder JC, Staisiunas PG, Meltzer DO, et al. Noise and Sleep Among Adult Medical Inpatients: Far From a Quiet Night. Arch Intern Med 2012; 172: 68 - 70
















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