Sleeping pills and Alzheimer’s disease – experts respond

Long term use of benzodiazepines widely prescribed for anxiety and insomnia, such as Valium and Xanax, is associated with an increased risk of developing Alzheimer’s disease, suggests a new study published today in the British Medical Journal

Credit: Miran Rijavec (Flickr)
Credit: Miran Rijavec (Flickr)

The team of French and Canadian researchers identified almost 1,800 cases of Alzheimer’s disease over a period of at least six years. They then compared each case with 7,000 healthy people matched for age, sex, and duration of follow-up.

The scientists found that past use of benzodiazepines for three months or more was associated with up to a 51 per cent increased risk of Alzheimer’s disease. The strength of association increased with longer exposure and when patients were prescribed long-acting benzodiazepines rather than short-acting ones.

According to 2011 statistics published by Alzheimer’s New Zealand, about 50 thousand people are currently diagnosed with dementia – jumping from 41 thousand people in 2008. By 2050 it’s estimated that just under 150 thousand New Zealanders will be diagnosed.

Our colleagues at the Australian and UK SMC have collected the following expert commentary. Feel free to use these quotes in your reporting. If you would like to contact a New Zealand expert, please contact the SMC (04 499 5476;

Dr Bryce Vissel, Head of the Neurodegeneration Research Laboratory at the Garvan Institute of Medical Research in Sydney, comments:

“This important study on Benzodiazepine use and risk of Alzheimer’s disease shows that taking widely prescribed drugs used to treat anxiety and insomnia is associated with an increased risk of developing Alzheimer’s disease. The study is particularly important given concerns that elderly patients may sometimes be over-medicated. It has been estimated that up to 50 per cent of older adults use these drugs. The potential long term consequences on brain health over time are likely to be missed in people adding to the growing prevalence of cognitive impairment among older people. This is therefore a health concern that must be considered.

“Dementia is emerging as one of Australia’s major health issues. There are more than 332,000 Australians living with dementia. This number is expected to increase by one third to 400,000 in less than ten years. Without a medical breakthrough, the number of people with dementia is expected to be almost 900,000 by 2050. Each week, there are more than 1,700 new cases of dementia in Australia; approx. one person every 6 minutes. This is expected to grow to 7,400 new cases each week by 2050.

“The results of this study show that past use of benzodiazepines for three months or more was associated with an increased risk (up to 51 per cent) of Alzheimer’s disease. Longer use of the drugs is associated with increased risk. The drugs in question, called benzodiazepines, are indisputably valuable for managing anxiety disorders and transient insomnia but the conclusion of this study is that these treatments should be used for short periods of time.
It is notable that the American Geriatrics Society updated its list of inappropriate drugs for older adults to include benzodiazepines, precisely because of their unwanted cognitive side effects. It is important to encourage physicians to carefully balance the benefits and risks when initiating or renewing a treatment with benzodiazepines and related products in elderly patients.”

Dr Liz Coulthard, Consultant Senior Lecturer in Dementia Neurology, University of Bristol, comments:

“This work provides yet another reason to avoid prescription of benzodiazepines for anything other than very short term relief of insomnia or anxiety. In addition to short term cognitive impairment, falls and car accidents already known to be associated with benzodiazepine use, there is a hint from this study that these drugs might in some way increase the risk of developing Alzheimer’s disease.

“However, we know that Alzheimer’s disease pathology accumulates for up to 17 years prior to diagnosis and this study looked at benzodiazepine use well into the course of the pathological cascade in the disease. In addition, retrospective studies such as this cannot prove causation. Therefore there is still a possibility that, rather than causing Alzheimer’s disease, benzodiazepines tend to be prescribed to patients presenting with anxiety or insomnia as part of an as yet undiagnosed dementia.

“To investigate further, future work should seek a plausible neurobiological mechanisms for the effect of benzodiazepines on Alzheimer’s pathology and, more broadly, the ongoing focus on earlier diagnosis of dementia will help associations to be teased apart from causative factors.”

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, comments:

“This study shows an apparent link between the use of benzodiazepines and Alzheimer’s disease although it’s hard to know the underlying reason behind the link.

“One limitation of this study is that benzodiazepines treat symptoms such as anxiety and sleep disturbance, which may also be early indicators of Alzheimer’s disease. We know that the processes that lead to Alzheimer’s could start more than a decade before any symptoms show. This study looks at benzodiazepine use five to ten years before diagnosis, and so the disease is likely to have already been present in some people.

“Benzodiazepines have been shown to cause memory problems as part of their side effects and so it is difficult to tease out cause and effect in studies such as this. We need more long-term research to understand this proposed link and what the underlying reasons behind it may be.”

Prof Gordon Wilcock, Emeritus Professor of Geratology, University of Oxford, comments:

“This carefully conducted study provides convincing evidence that the use of benzodiazepines may contribute to the development of Alzheimer’s disease, and importantly may be another factor we could modify to reduce the occurrence of dementia. However, these drugs would have been given to treat symptoms and it is possible that the latter may have been the earliest signs of unrecognised Alzheimer’s disease, although the authors have tried to control for this as far as was possible in their study. Ideally more research needs to be undertaken, but it will be difficult to do this prospectively as most clinicians would avoid long term prescription of these drugs in older people.”

Prof Guy Goodwin, President of the European College of Neuropsychopharmacology (ECNP), comments:

“Many treatments can look bad because they are given to sick people. This is “Confounding by indication”, and is the bane of all epidemiological studies of drug exposure. This publication recognizes the problem but may not have an adequate solution. The finding that benzodiazepine exposure is associated with the diagnosis of Alzheimer’s disease 5 years or more later could mean that the drugs cause the disease, but is more likely to mean that the drugs are being given to people who are already ill. In other words, we are seeing an association, rather than a cause.

“Non-specific symptoms arise in the 14 years before an Alzheimer diagnosis, so a 5 year study, as in this paper, may not be long enough to exclude what we call reverse causality; in other words symptoms in the early phases of Alzheimer’s disease may increase the probability of being prescribed a benzodiazepine. It is very difficult to control for this in most databases because the detail is insufficient to reconstruct the clinical reality.

“Nevertheless, benzodiazepines can impair memory by their direct effect on the brain (unrelated to dementia), and their use in the elderly always merits caution and care to balance side-effects with benefits.”

Prof John Hardy, Professor of Neuroscience, UCL, comments:

“The apparent association between benzodiazepines and Alzheimer’s disease is interesting and deserves further investigation. There are many possible explanations: it could be a true association in that it reflects benzodiazepine use in the early stage of disease (this is the reverse causation discussed by the authors), it could be caused by benzodiazepine causing minor brain damage which is clinically additive to Alzheimer disease, there could be a direct relationship between benzodiazepine drug action and the disease process, or it could be a false positive, a statistical fluke. Clearly more work is needed before any firm conclusions are drawn. Clinicians are already careful about benzodiazepine prescribing so I would not regard this unexplained and as yet unreplicated study as cause for any alarm.”