Use of hypnotic sleep-aids was associated with a higher mortality risk than that seen in non-users, according to the results of the latest case-controlled study published in BMJ Open. Patients prescribed as few as 0.4 to 18 doses of these sleep aids per year were found to have a mortality risk three to five times higher than people who used none at all. Given that 6 to 10 percent of Americans take these medications, the results of the study have been setting off alarms.
While earlier studies have linked prescription medications for insomnia with increased mortality, and even cancer risk, these studies were riddled with various confounders. Unlike the latest study, they contained limited information about the type and quantity of hypnotics used, as well as a paucity of data about the side effects of newer, short-acting hypnotics such as zolpidem (Ambien), zaleplon (Sonata/Stamoc), and eszopiclone (Lunesta).
For the current study, researchers from the Scripps Clinic in La Jolla, Calif., attempted to address some of these issues. They gathered data from more than 10,000 adult patients who had received at least one prescription for a hypnotic drug, then matched them with over 23,000 control patients who did not use a sleep aid. After 2.5 years of follow-up, 6.1 percent of hypnotic users had died, compared to 1.2 percent of patients in the control group. Researchers also noted that the mortality risk rose in accordance with the number of pills prescribed annually: Those who were prescribed over 132 doses per year suffered a five-fold increased risk of death.
Although the authors acknowledge that they were unable to control for certain biases that might otherwise explain their results, they maintain that the consistency of our estimates across a spectrum of health and disease suggests that the mortality effect of hypnotics was substantial.
But Dr. Ross remains largely unimpressed with the study conclusions, primarily because there is no clear biological plausibility. Until someone can explain to me how a small number of hypnotic sleep aid doses can increase mortality by three- to five-fold over such a brief period, he says, I will remain convinced that unmeasured confounders play the major role in this association. For instance, a connection to depression or alcohol use may have been a significant factor which the study did not control for.
While conceding that the study results do not prove cause and effect, the researchers still advise that those with sleep problems reconsider even short-term use of hypnotics and try cognitive behavioral therapy instead. This advice is condescending and largely unrealistic, counters Dr. Ross, noting the considerable toll that insomnia takes on chronic sufferers. Unfortunately, the only way to rigorously dispute these results is with a randomized controlled prospective trial. However, this may be impractical due to ethical limitations.