Sleeping Pills May Dramatically Increase Death Rate

A study of electronic medical records suggests that sleeping pill use may be associated with up to 500,000 additional deaths per year.

Hypnotic sleeping pills dramatically increase one’s risk of dying, even at relatively low rates of use, according to results of an observational study published in the online journal BMJ Open. The results also found that medium-to-high rates of sleeping pill use were associated with a substantial increase in the risk of developing cancer.

Hypnotics are among the most commonly prescribed drugs in the United States, with an estimated 6% to 10% of adults having taken them to aid in sleep in 2010. Well over a dozen studies dating back more than 3 decades have found an increased mortality associated with sleeping pill consumption. Newer, shorter-acting sleeping pills such as zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta), however, have come to dominate the market in part because they are believed to be safer than older sleeping pills.

The authors of the current study, led by Daniel F. Kripke, MD, of the Scripps Clinic Sleep Center in La Jolla, California, used longitudinal electronic medical records to determine the risk of death and cancer associated with newer and older sleeping pills compared with controls. The records, for 10,529 patients who received sleeping pill prescriptions and 23,676 matched controls, were drawn from the Geisinger Health System, which serves a rural area of Pennsylvania. Subjects in the study, who had an average age of 54 years, were followed for an average of 2.5 years between 2002 and 2007.

The results showed that the raw death rate for all users of sleeping pills was 4.86 times higher than that of non-users. After adjustment for demographic and lifestyle factors as well as a range of comorbidities, the death rate for users was still 4.56 times that of nonusers. Most surprisingly, even those in the lowest third of sleeping pill consumption (0.4 to 18 doses per year) were 3.6 times more likely to die. Those in the middle third of consumption (18 to 132 doses per year) were 4.43 times more likely to die, and those in the top third (more than 132 doses per year) were 5.32 times more likely to die, suggesting a dose-response relationship.

Sleeping pill users in the middle third had a 20% increased risk of developing a new major cancer, whereas those in the top third of users had a 35% increased risk. Zolpidem users in the top third had a 28% increased risk of major cancer. Temazapam users in the middle third had a 44% increased risk of major cancer, and users in the top third had a 99% increased risk.

The study’s results indicated that the increased risk of death and developing cancer associated with sleeping pill use was not attributable to pre-existing diseases. The researchers note that the ways that sleeping pills may increase mortality include lethality in combination with alcohol or other drugs; increased levels of depression and suicide; increased rate of automobile crashes and falls; increased sleep apnea, which can contribute to automobile crashes and cardiovascular problems; and night-eating syndromes, which can lead to poor diet and obesity. They also note that the increased risk of lymphomas and lung, colon, and prostate cancers among sleeping pill users were all higher than that for current smokers, indicating the likelihood that the cancers were caused by specific biologic mechanisms.

By extrapolating their findings to the entire US population, the researchers estimate that sleeping pills may have been associated with 320,000 to 507,000 excess deaths in 2010. The researchers note that it is possible that their study failed to account for other causes of increased mortality among sleeping pill users, such as depression, anxiety, and other emotional factors, which are kept confidential due to Pennsylvania law. In addition, they note that the study was unable to verify that drugs prescribed to the users were actually dispensed and consumed, nor was it able to account for the possibility that nonusers may have consumed OTC anithistamines or sleeping pills prescribed to others. A randomized, clinical trial could avoid these shortcomings, although the researchers note that running such a trial would likely be seen as unethical.