Anxiety, Sleeping Pills Tied to Increased Death Risk

Patients who took anti-anxiety or hypnotic drugs had a markedly increased risk of death, which became even more marked with increased consumption of the medications or longer use, a new study finds.

Taking medications to treat anxiety and sleep disorders may double one’s risk of death, according to a study published online on March 19, 2014, in BMJ.

Although previous research has indicated an association between anti-anxiety or hypnotic drugs and an increased risk of premature mortality, the relationship remains unclear. The current study used primary care prescription records from 273 primary care practices in the United Kingdom contributing to the General Practice Research Database to test the association of the medications and mortality risk after adjusting for a wide range of potential confounders. Patients aged 16 and older who were first prescribed anti-anxiety or hypnotic drugs, or both, from 1998 to 2001 were each matched with 2 controls who had never been prescribed the medications. Medications were quantified by their daily dose and were classified as benzodiazepines, Z drugs (zaleplon, zolpidem, and zopiclone), or other. Patients were followed for 7.6 years on average.

The results indicated that taking either anti-anxiety or hypnotic drugs was significantly associated with mortality at all levels of medication use. When the analysis was restricted to patients who only received the medications during the first year of observation, this relationship remained significant, with a hazard ratio of 3.32, after adjustment. The association followed a dose-response pattern, and those who received more than 90 daily doses of any anti-anxiety or hypnotic drug had an adjusted hazard ratio for mortality of 4.51. Patients who only took the medications during the first year and survived were less likely to die than those who continued taking the drugs after 1 year; 18.8% of patients who took the medications only during the first year died, compared with 22% of those who continued to use them after the first year.

Among patients who were prescribed the medications, the crude cumulative mortality over the duration of the follow-up period was 26.46 per 100 patients, compared with 16.82 per 100 controls. When deaths that occurred in the first year of follow-up were excluded from the analysis, approximately 4 excess deaths were associated with drug use per 100 patients over the full follow-up period.

The relationship between mortality and use of the medications was found for each of the 3 drug classes analyzed in the study, and the hazard ratios were largest for benzodiazepines. Benzodiazepines were also the most commonly prescribed drug class, with 63.7% of patients who were prescribed medications covered by the study receiving benzodiazepines.

Although the study’s results are consistent with previous research, its authors note that they are still susceptible to confounding and bias. “These results add to evidence of an association with mortality, but must be treated with caution,” they conclude.