Common sleeping pills are linked to increased risk of death, reveals study published in BMJ.
These medications were also associated at higher doses with a 35-percent increased risk of cancer as compared with non-users, but the reason for this is unclear.
Doctors led by Daniel Kripke of the Scripps Clinic Viterbi Family Sleep Center in La Jolla, California, looked at the medical records of more than 10,500 adults living in Pennsylvania who were taking prescribed sleeping aids.
These were compared against more than 23,600 counterparts, matched for age, health and background, who did not take these drugs.
The study ranged over two and a half years, and looked at widely-prescribed sleeping pills, including benzodiazepines, non-benzodiazepines, barbiturates and sedatives.
The overall number of deaths that occurred during this period was small in both groups, being less than a thousand in total.
But there was a striking difference in mortality, the researchers found.
Those who took between 18 and 132 doses of the pills per year were 4.6 times likelier to die than the "control" group.
Even those who took less than 18 annual doses were more than 3.5 times likelier to die.
"Rough order-of-magnitude estimates... suggest that in 2010, hypnotics (sleeping pills) may have been associated with 320,000 to 507,000 excess deaths in the USA alone," says the study.
Details of how individuals died were not disclosed, and the authors stress that they have found a statistical link but not a cause.
But they sound the alarm, given the vast number of people who take these drugs.
"We estimate that approximately six to 10 percent of US adults used these drugs in 2010 and the percentages may be higher in parts of Europe," they write.
The average age of the people in the study was 54. The researchers say they took into account factors that could skew the comparison between the two groups, such as whether an individual smoked or had a pre-existing health condition.
However, they were unable to take depression, anxiety and other emotional factors into account, as these diagnoses are kept secret under Pennsylvania law.
Previous research into sleeping pills has found a link with car accidents and serious falls, "night-eating syndromes" of bingeing on food, regurgitation in the oesophagus and peptic ulcer disease.