Certain commonly prescribed sleeping pills are associated with a more than fourfold increased risk of death, even among those taking fewer than 18 doses a year, indicates research published in the online journal BMJ Open.

And these drugs are also associated with a significantly increased risk of cancer among those taking high doses, the study shows.

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 so.

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 sufficiently safe."

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 sleeping pills."

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