A new study suggests that people who take sleeping pills are more likely to die within a couple of years than those who don’t, though it doesn’t prove that the pills caused people to die before they otherwise would have — and outside experts say patients shouldn’t panic and toss their medications.
The study is published in BMJ Open, an open-access online journal. (Here’s its open peer-review policy.)
It looked at 10,531 patients served by the Geisinger Health System who had a new or existing prescription for sleep drugs — both older varieties and newer ones, such as Ambien. It also looked at 23,676 similar patients who weren’t taking the drugs.
Comparing the groups showed a higher risk of death within the follow-up period — an average of 2.5 years — for people taking the drugs. The increased risk of death was largest for those prescribed more doses per year (at 5.3 times higher for those prescribed more than 132 doses per year) but a risk 3.6 times higher was observed even at 18 or fewer doses per year. The increased risk of death associated with the drugs was higher than in previous studies.
The authors also saw a 35% higher risk of cancer among patients prescribed the drugs compared to those who weren’t prescribed them.
Still, there were limitations to the study; by dint of its design, it can’t show that the drugs actually killed people. “Just because they found an association … doesn’t mean that [the drugs] caused death,” says Shelby Harris, director of the behavioral sleep medicine program at Montefiore Medical Center. (Harris wasn’t involved in the research.)
The study authors say they controlled for health problems including asthma, obesity and diabetes, but they couldn’t take into account depression, anxiety or other psychiatric problems because of state laws covering the confidentiality of those diagnoses. It’s possible that people taking the drugs had those or other underlying problems that made them more likely to die early.
The research also didn’t identify the cause of death for any of the 638 people taking the drugs or the 295 people not taking the drugs who passed away during the follow-up period. Were the drug users more likely to be killed in car crashes or other accidents, for example? Or did they mostly die of cancer? We don’t know.
Sanofi, which makes Ambien, said in statement that the study had further limitations beyond those identified by the authors and that “the conclusions drawn based on the data presented are highly questionable.” Among its concerns: the average follow-up was about 2.5 years, which it says would be too short to accurately gauge a cause and effect relationship with cancer or death.
Daniel Kripke, an author of the study and a physician at the Scripps Clinic Viterbi Family Sleep Center, says a randomized controlled trial studying these drugs would be unethical because of this and the 18 other studies suggesting a significantly higher risk of death. “What I’d tell a patient taking these drugs is that it’s quite possible that our estimate of the size of risk is wrong — either too high or too low — but it’s quite unlikely” that there isn’t a causal link, he says.
But Virend Somers, a cardiologist at the Mayo Clinic who studies sleep and who wasn’t involved with the study, says that if there is a cause and effect relationship, it will likely take a randomized trial to convince doctors to change their prescribing habits. And such a study could be feasible, given the results seen in a short time frame in this study.
Absent the results of a randomized trial — the gold standard of scientific evidence — what’s a doctor or patient to do? “As we think about prescribing these drugs, we should bear in mind: if there is a mortality and/or a cancer risk, is that worth the potential benefit?” says Somers.
As for patients, “the dosages and the reasons for being prescribed these drugs vary so widely, it’s appropriate for any particular person to call their prescribing physician and discuss the study,” he says.
Harris says there are alternatives to drugs for sleep problems, including cognitive behavioral therapy, that often work as a first-line treatment.
We reached out to the Pharmaceutical Research and Manufacturers of America (PhRMA), for their reaction. The group says it hasn’t had a chance to review the study, but in a statement says that prescription drugs undergo thorough clinical trials before approval and are monitored for safety problems after approval. “Medications to treat sleep disorders are an important part of addressing difficulty sleeping for many patients and, while we are not able to comment on the specific findings of this study, it is important that patients work with their doctors to understand the benefits and risks of all of their medicines.”