Some sleeping pills are linked to a more-than fourfold risk of premature death, according to an American study published in the journal BMJ Open on Monday.
These medications were also associated at higher doses with a 35-percent increased risk of cancer as compared with non-users, but the reason for this is unclear.
Doctors led by Daniel Kripke of the Scripps Clinic Viterbi Family Sleep Center in La Jolla, California, looked at the medical records of more than 10,500 adults living in Pennsylvania who were taking prescribed sleeping aids. These were compared against more than 23,600 counterparts, matched for age, health and background, who did not take these drugs.
The study ranged over two and a half years, and looked at widely-prescribed sleeping pills, including benzodiazepines, non-benzodiazepines, barbiturates and sedatives. The overall number of deaths that occurred during this period was small in both groups, being less than a thousand in total.
But there was a striking difference in mortality, the researchers found.
Objectives An estimated 6%–10% of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality.
Setting A large integrated health system in the USA.
Design Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis.
Subjects Subjects (mean age 54 years) were 10 529 patients who received hypnotic prescriptions and 23 676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 years between January 2002 and January 2007.
Main outcome measures Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards models controlled for risk factors and using up to 116 strata, which exactly matched cases and controls by 12 classes of comorbidity.
Results As predicted, patients prescribed any hypnotic had substantially elevated hazards of dying compared to those prescribed no hypnotics. For groups prescribed 0.4–18, 18–132 and >132 doses/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36) and 5.32 (4.50 to 6.30), respectively, demonstrating a dose–response association. HRs were elevated in separate analyses for several common hypnotics, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates and sedative antihistamines. Hypnotic use in the upper third was associated with a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55). Results were robust within groups suffering each comorbidity, indicating that the death and cancer hazards associated with hypnotic drugs were not attributable to pre-existing disease.
Conclusions Receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death even when prescribed <18 pills/year. This association held in separate analyses for several commonly used hypnotics and for newer shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality.