Long-term users of benzodiazepines, drugs used to treat anxiety and insomnia, may be at increased risk of developing Alzheimer’s disease, according to a new study published in the BMJ.
The main cause of dependency in older people, dementia currently affects about 36 million people worldwide. This number is expected to double every 2 decades because of population growth, reaching an estimated 115 million in 2050.
There are no effective treatments for dementia, so identifying modifiable risk factors is essential to avoid these forecast human consequences and social costs.
Previous research has identified an increased risk of dementia among benzodiazepine users, but the mechanism behind the association – as well as the dosage linked to the risk – has not been clear.
Mainly used to treat anxiety and insomnia, benzodiazepines are widely used in developed countries, particularly among the elderly. Because of strong withdrawal symptoms, and because long-term effectiveness of the benzodiazepines remains unproved, international guidelines recommend only short-term use of the drugs.
However, although benzodiazepines are known to affect memory and cognition, proving that they contribute to onset of dementia symptoms is not easy. This is partly because the symptoms that benzodiazepines are prescribed to treat – anxiety, insomnia, depression – are also symptoms experienced in the years before dementia is diagnosed.
The researchers tracked development of Alzheimer’s disease among a sample of elderly people who had been prescribed benzodiazepines in Quebec, Canada, by examining data from the Quebec health insurance program database.
Over a study period of 6 years, the researchers identified 1,796 cases of Alzheimer’s disease. Each case was matched for age, sex and duration of follow-up, and compared with healthy people from a group of 7,184 control subjects.
The study found that benzodiazepine use for 3 months or more was associated with an increased risk of Alzheimer’s disease of up to 51%. The longer the exposure to benzodiazepines, the greater the risk of Alzheimer’s. Long-acting benzodiazepines were also found to increase risk more than short-acting benzodiazepines.
The researchers report that adjusting for symptoms that might suggest dementia onset – such as anxiety, depression or sleep disorders – “did not meaningfully alter the results.”
Although the researchers designed the study specifically to reduce “reverse causation bias” – where cause and effect are mixed up – they admit they cannot completely rule out the possibility that “benzodiazepine use might be an early marker of a condition associated with an increased risk of dementia and not the cause.”
The authors state that their findings are of “major importance for public health, especially considering the prevalence and chronicity of benzodiazepine use in elderly populations and the high and increasing incidence of dementia in developed countries.”
“It is now crucial to encourage physicians to carefully balance the benefits and risks when initiating or renewing a treatment with benzodiazepines and related products in elderly patients,” they add.
In a related editorial, Prof. Kristine Yaffe, of the University of California at San Francisco, and Prof. Malaz Boustani, of the Indiana University Center for Aging Research, say that despite benzodiazepines being added to the American Geriatrics Society’s list of inappropriate drugs for older adults in 2012, almost 50% of older adults continue to use them.
Yaffe and Boustani suggest that a formal monitoring system may be necessary to predict the long-term consequences of these drugs on brain health.