Commonly prescribed sleeping pills linked to fourfold increased risk
28 February 2012
A study of over 30,000 patients has found that a number of
commonly prescribed sleeping pills are associated with a more than
fourfold increased risk of death.
The association was found even among those taking very few doses —
less than 18 doses a year. The study found the same group of drugs
are also associated with a significantly increased risk of cancer
among those taking high doses.
The research is published in the online journal BMJ Open
In 2010 between one in 20 and one in 10 adults took a sleeping
pill in the US alone, say the authors, who tracked the survival of
over 10,500 people with a range of underlying conditions, who were
prescribed a range of sleeping pills for an average of 2.5 years
between 2002 and 2007.
The drugs included benzodiazepines, such as temazepam;
non-benzodiazepines, such as zolpidem, eszopiclone, and zaleplon;
barbiturates; and sedative antihistamines.
The survival of these patients, whose average age was 54, was
then compared with that of over 23,500 people matched for age, sex,
lifestyle factors, and underlying health problems, but who had not
been prescribed sleeping pills over the same period.
After taking account of factors likely to influence the results,
including age, sex, weight, lifestyle, ethnicity and previously
diagnosed cancer, the results pointed to a link between these drugs
and an increased risk of death, even at relatively low doses.
Those prescribed up to 18 doses a year were more than 3.5 times
as likely to die as those prescribed none, while those prescribed
between 18 and 132 doses were more than four times as likely to do
And those taking the most doses (132+ a year) were more than five
times as likely to die as those prescribed none, indicating that the
level of risk rose in tandem with increasing doses, say the authors.
These associations were found in every age group, but were greatest
among those aged 18 to 55.
Supplementary material posted alongside the paper shows 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.
Those taking the highest number of doses were also at greater
risk of developing several types of cancer, and 35% more likely to
be diagnosed with any type of cancer, overall. This association was
not explained by pre-existing poor health, the data showed.
The authors point out that studies showing association don't
necessarily prove cause and effect. But their findings back up
previous research showing an increased risk of death among users of
sleeping pills, they say.
Agreement is beginning to build that alternatives to sleeping
pills for the treatment of insomnia may be warranted, they write.
And they ask if it isn't time to reconsider "whether even the
short term use of hypnotics, as given qualified approval in National
Institute for Health and Clinical Excellence [NICE] guidance, is
BMJ Open editor in chief, Dr Trish Groves, comments:
"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. So these findings raise
important concerns and questions about the safety of sedatives and
Kripke FK, Langer RD, Kline LE. Hypnotics' association with
mortality or cancer: a matched cohort study. BMJ Open 2012.