A new study finds that people who take certain commonly prescribed sleeping pills have a five-fold increased risk of death, even among those taking fewer than 18 doses a year.
And these drugs are also linked to a significantly increased risk of cancer among those taking high doses, the study, published in the journal BMJ Open, shows.
The study, analyzing 10,500 people who took a wide-range of sleeping pills including zolpidem, diazepam and tamazepam, found that the top third of sleeping pill users had a 5.3-fold higher death risk and also had a 35 percent higher risk of cancer. And people who were on higher doses of tamazepam were six times as likely to die in the next 30 months, the study found.
“We are not certain. But it looks like sleeping pills could be as risky as smoking cigarettes. It looks much more dangerous to take these pills than to treat insomnia another way,” study leader Daniel F. Kripke, MD, told WebMD.
The sleeping pills in question are known as hypnotics and include such brands as Ambien and Restoril. Hypnotic sleeping pills actually cause a person to fall asleep. This is in contrast to other sleeping aids, such as melatonin, which promote sleep through relaxation. Kripke and colleagues said other dangerous hypnotic sleeping aids include Lunesta, Sonata, Halcion, and Dalmane.
Kripke, retired professor of psychiatry at the University of California, San Diego, began studying the effects sleeping pills have on the risk of death in 1975. Since then, he has co-published 18 studies finding links between the two.
In the latest study, Kripke and colleagues analyzed data from a large Pennsylvania health system from between 2002 and 2007. They obtained medical records for 10,529 people who used prescribed hypnotic sleeping pills and for 23,676 matched patients who were never prescribed sleeping pills.
Over an average of 2.5 years, the death rate for those who did not use sleeping pills was 1.2 percent. For those who were prescribed sleeping pills the death rate climbed to 6.1 percent.
And after taking into account factors likely to influence the results – including age, sex, weight, lifestyle, ethnicity and previously diagnosed cancer – the study´s results pointed to a 3.6-fold higher death rate in those who only took 18 or fewer doses.
Based on their findings, Kripke and colleagues estimate that sleeping pills are linked to between 320,000 and 507,000 US deaths each year.
“We think these sleeping pills are very dangerous. We think they cause death. We think they cause cancers,” said Kripke. “It is possible but not proven that reducing the use of these pills would lower the U.S. death rate.”
The associations of increased death risk was found in every age group, but were greatest among those aged 18 to 55. Supplemental material published alongside the paper showed that, although the overall numbers of deaths in each group were quite small, there were clear differences among them.
For example, there were 265 deaths among 4,336 people taking zolpidem, compared with 295 deaths among the 23,671 people who had not taken sedatives or sleeping pills.
Kripke pointed out that studies showing association do not necessarily prove cause and effect, however. But the findings do back up previous research showing an increased risk of death among sleeping pill users, he added.
“The meager benefits of hypnotics [sleeping pills], as critically reviewed by groups without financial interest, would not justify substantial risks,” wrote Kripke. “A consensus is developing that cognitive-behavioral therapy of chronic insomnia may be more successful than hypnotics.”
Sleeping pills are thought to also increase risk of depression and can impair driving skills. Kripke has passed the study findings on to the US Food and Drug Administration (FDA), the watchdog to the US pharmaceutical industry. The authors of the study said their findings, together with similar findings in previous studies, should be used by authorities to re-assess whether even modest doses of sleeping pills are safe.
“Although the authors have not been able to prove that sleeping pills cause premature death, their analyses have ruled out a wide range of other possible causative factors,” wrote Dr Trish Groves, editor in chief of BMJ Open. “So these findings raise important concerns and questions about the safety of sedatives and sleeping pills.”
National Health Service (NHS) guidelines recommend zolpidem should only be used at the lowest possible dose and for a maximum of up to four weeks. Zaleplon should only be used at the lowest possible dose and for a maximum of up to two weeks, while temazepam should be taken for a maximum of four weeks.
Most of those in Kripke´s study were taking Ambien or Restoril. Sanofi-Aventis, the maker of Ambien, noted that Kripke´s study had a number of faults.
“Ambien has more than 17 years of real-world experience and is safe and effective when prescribed and taken according to its labeling,” Sanofi told WebMD in a statement. “Ambien should be prescribed in strict adherence to its labeling and patients should take their medication as prescribed. The Ambien labeling carries specific warnings against driving and against intake of alcohol together with Ambien.”
And although experts note the Kripke study certainly raises concerns, they said it does not prove that sleeping pills kill.
This “very provocative and interesting study raises a lot of questions,” Nancy Collop, MD, president of the American Academy of Sleep Medicine and director of the Sleep Center at Emory University School of Medicine, told WebMD.
“You cannot assume, just because you find this kind of association, that hypnotics are killing people,” she said. “People who go on sleeping pills are a sicker population. I know they tried to control for that, but these people simply are not as healthy.”
Michael Yurcheshen, MD, head of the sleep fellowship program and assistant professor of neurology at the University of Rochester, NY, noted that much can be missed in a study that looks back at medical records rather than at the patients themselves.
“It is implausible to think that so many of these medications, spread across several different drug classes, could have the same biological effects,” Yurcheshen told WebMD.
Yet, both Collop and Yurcheshen praise Kripke for raising the issue of sleeping pill dangers.
“One part of the Kripke study I really did like is when they point out that part of the problem with hypnotics is they are really best for people with acute, short episodes of insomnia,” Yurcheshen said. “Very few insomnia drugs are approved for long-term daily use. And so it is fair to say that the long-term safety of these drugs has never been explored for use in that way.”
Collop said she is torn on the issue of whether hypnotics are “good or bad.” She noted that it can be harmful to be dependent on hypnotic sleeping pills for a long period of time. But they can be very helpful to those who are having great difficulty in falling asleep for some specific reason.
She noted that sleeping pills are mainly short-term use aids. “So the ideal patient would be someone with a very high stress level for some reason, such as the recent loss of loved one or a divorce, or for a traveler adjusting to a new time zone. This should be for a limited time period and only as needed, not on a nightly basis. In such situations these drugs are appropriate and effective,” she told WebMD.
Kripke, colleagues and the experts all agree that a form of short-term psychotherapy — cognitive behavioral therapy — is surprisingly effective for people with chronic insomnia.
Collop says it´s time to see a sleep specialist if you have tried sleeping pills and they don´t work anymore. Looking for another brand of sleeping pill will not work.
Nina Barnett, spokesperson for the Royal Pharmaceutical Society told The Telegraph: “This is an important study and although it is unlikely to radically change prescribing in the immediate term, it should raise awareness and remind both patients and prescribers to the potential risks of sedative use for insomnia.”
“The association between mortality and sedation is not new and this research tells us is that people who took these medicines were more likely to die than people who didn´t take them. However it does not mean that the deaths were caused by the medicine,” she added. “Patients should not stop taking any prescribed medicines straight away. If you are concerned about your medicines discuss this with your pharmacist or Doctor about other ways of getting help with sleep problems so you don´t have to use medicines.”
On the Net:
- BMJ Open
- University of California, San Diego
- Food and Drug Administration (FDA)
- National Health Service (NHS)
- American Academy of Sleep Medicine
- Sleep Center, Emory University School of Medicine
- University of Rochester
- Royal Pharmaceutical Society