Anxiolytic, hypnotic drugs may be associated with increased long-term mortality

Anxiolytic and hypnotic drugs may be associated with increased long-term mortality, according to a new study.

Researchers in the United Kingdom performed a retrospective cohort study using data from 273 primary care practices to examine whether anxiolytic and hypnotic drugs were related to increased risk for premature death. Study drugs were divided into 3 classes: benzodiazepines, “Z” drugs (zaleplon, zolpidem, and zopiclone), and any other anxiolytic or hypnotic drugs. (Zopiclone is not commercially available in the United States.) All included patients were required to be at least 16 years of age and to have received at least 2 prescriptions of a study drug, one of them a first-ever prescription, between January 1998 and December 2001. These patients were matched by age, sex, and practice with controls who did not receive any of the study drugs during this period. The study's main outcome measure was all-cause mortality as determined from primary care practice records. Results were published online March 19 by BMJ.

The study included data from 34,727 patients who received the study drugs and 69,418 matched controls who did not. Overall, 76.3% of patients in the study-drug group received a prescription for a benzodiazepine, 38.8% received a prescription for a “Z” drug, and 13.4% received a prescription for 1 or more other study drugs. Diazepam, temazepam, and zopiclone were the individual drugs most commonly prescribed. After a mean follow-up of 7.6 years, the researchers found that patients who were prescribed the study drugs had a significantly higher prevalence of physical and psychiatric comorbid conditions, as well as a higher prevalence of prescriptions for other drugs.

Patients who used any of the study drugs during the first year after recruitment into the study had an age-adjusted hazard ratio of 3.46 (95% CI, 3.34 to 3.59) for mortality over the follow-up period; this hazard ratio was 3.32 (95% CI, 3.19 to 3.45) after adjustment for additional potential confounders. All 3 classes of study drugs showed a dose-response relationship. The researchers excluded deaths in the first year of the study and calculated that approximately 4 excess deaths per 100 people were related to use of the study drugs over the follow-up period.

The authors concluded that their findings support previous evidence pointing to an association between anxiolytic and hypnotic drugs and mortality but noted that their results should be interpreted with care because of the potential effect of important limitations. “While we have largely excluded immortal time bias and selection bias, we are unable to exclude the possibility that the results were due to confounding by indication or to residual confounding by unmeasured or incompletely measured factors, such as socioeconomic status,” the authors wrote. “This applies especially to deaths in the first year of observation.”