BMJ 2014;349:g5555 doi: 10.1136/bmj.g5555 (Published 10 September 2014)
Page 1 of 1
Research News
RESEARCH NEWS Benzodiazepines may be linked to Alzheimer’s disease, study finds Zosia Kmietowicz The BMJ
Taking benzodiazepines is associated with an increased risk of developing Alzheimer’s disease, particularly in long term users, a study has found.
Benzodiazepine use has long been associated with an increased risk of Alzheimer’s disease, although whether this association is causal remains unclear. To try to better understand the association, a team of researchers from France and Canada used data from the Quebec health insurance programme database (RAMQ) to track the development of Alzheimer’s in a sample of elderly residents living in Quebec, Canada, who had been prescribed benzodiazepines.1 Over a period of at least six years they identified 1796 cases of Alzheimer’s disease. They then compared these cases with 7184 healthy people matched for age, sex, and duration of follow-up.
The authors reported in The BMJ that previous use of benzodiazepines for three months or more was associated with a 51% increased risk of Alzheimer’s disease (adjusted odds ratio 1.51 (95% confidence interval 1.36 to 1.69)). The strength of the association increased with longer exposure to benzodiazepines (1.31 (1.01 to 2.74) with 91 to 180 prescribed daily doses; 1.84 (1.62 to 2.08) with more than 180 prescribed daily doses). Long acting benzodiazepines were also more strongly associated with Alzheimer’s than those with a shorter half life (1.43 (1.27 to 1.51) with short acting drugs; 1.70 (1.46 to 1.98) with long acting drugs). Further adjustment for symptoms that might indicate the start of dementia, such as anxiety, depression, or sleep disorders, did not meaningfully alter the results. The authors emphasised that the nature of the link between benzodiazepines and Alzheimer’s was still not definitive but that the stronger association seen with long term exposure to the drugs “reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia.”
For personal use only: See rights and reprints http://www.bmj.com/permissions
They concluded that it was “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.”
In a commentary, specialists in psychiatry and ageing research noted that, in 2012, the American Geriatrics Society had updated its list of inappropriate drugs for older people to include benzodiazepines, precisely because of their unwanted cognitive side effects.2 Yet almost half of older people continued to use these drugs, they wrote. And without any formal monitoring system, the potential long term consequences on brain health were likely to be missed, they warned, adding that the surveillance of cognitive side effects in these patients needed to be improved. Commenting on the study, Guy Goodwin, president of the European College of Neuropsychopharmacology, said, “Non-specific symptoms arise in the 14 years before an Alzheimer diagnosis, so a five 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.” 1 2
Bilioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer’s disease: case control study. BMJ 2014;349:g5205. Yaffe K, Scola M, Boustani M, Fairbanks RM. Benzodiazepines and risk of Alzheimer’s disease. BMJ 2014;349:g5312.
Cite this as: BMJ 2014;349:g5555 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
Page 1 of 1
Research News
RESEARCH NEWS Benzodiazepines may be linked to Alzheimer’s disease, study finds Zosia Kmietowicz The BMJ
Taking benzodiazepines is associated with an increased risk of developing Alzheimer’s disease, particularly in long term users, a study has found.
Benzodiazepine use has long been associated with an increased risk of Alzheimer’s disease, although whether this association is causal remains unclear. To try to better understand the association, a team of researchers from France and Canada used data from the Quebec health insurance programme database (RAMQ) to track the development of Alzheimer’s in a sample of elderly residents living in Quebec, Canada, who had been prescribed benzodiazepines.1 Over a period of at least six years they identified 1796 cases of Alzheimer’s disease. They then compared these cases with 7184 healthy people matched for age, sex, and duration of follow-up.
The authors reported in The BMJ that previous use of benzodiazepines for three months or more was associated with a 51% increased risk of Alzheimer’s disease (adjusted odds ratio 1.51 (95% confidence interval 1.36 to 1.69)). The strength of the association increased with longer exposure to benzodiazepines (1.31 (1.01 to 2.74) with 91 to 180 prescribed daily doses; 1.84 (1.62 to 2.08) with more than 180 prescribed daily doses). Long acting benzodiazepines were also more strongly associated with Alzheimer’s than those with a shorter half life (1.43 (1.27 to 1.51) with short acting drugs; 1.70 (1.46 to 1.98) with long acting drugs). Further adjustment for symptoms that might indicate the start of dementia, such as anxiety, depression, or sleep disorders, did not meaningfully alter the results. The authors emphasised that the nature of the link between benzodiazepines and Alzheimer’s was still not definitive but that the stronger association seen with long term exposure to the drugs “reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia.”
For personal use only: See rights and reprints http://www.bmj.com/permissions
They concluded that it was “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.”
In a commentary, specialists in psychiatry and ageing research noted that, in 2012, the American Geriatrics Society had updated its list of inappropriate drugs for older people to include benzodiazepines, precisely because of their unwanted cognitive side effects.2 Yet almost half of older people continued to use these drugs, they wrote. And without any formal monitoring system, the potential long term consequences on brain health were likely to be missed, they warned, adding that the surveillance of cognitive side effects in these patients needed to be improved. Commenting on the study, Guy Goodwin, president of the European College of Neuropsychopharmacology, said, “Non-specific symptoms arise in the 14 years before an Alzheimer diagnosis, so a five 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.” 1 2
Bilioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer’s disease: case control study. BMJ 2014;349:g5205. Yaffe K, Scola M, Boustani M, Fairbanks RM. Benzodiazepines and risk of Alzheimer’s disease. BMJ 2014;349:g5312.
Cite this as: BMJ 2014;349:g5555 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
