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Benzodiazepine use and risk of dementia: prospective population based study

BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e6231 (Published 27 September 2012) Cite this as: BMJ 2012;345:e6231

Re: Benzodiazepine use and risk of dementia: prospective population based study

First of all, we would sincerely like to thank Bocti and colleagues and Coyle-Gilchrist and colleagues for their interest and for providing such fruitful comments about our article.

Most of them, directly or indirectly, focus on the possibly non-causal nature of the association we found between benzodiazepines (BZDs) and dementia. To make this point clear, we never concluded that this association was causal. We designed our study in order to attempt to go further than previously published studies by minimizing possible confounding and reverse causation biases. Among others, this is the reason why our analyses considered only actual incident and not prevalent users at the expense of a drastic reduction in sample size.

Both rapid responses pointed out that symptoms that are possible indications for BZD prescription (anxiety, sleep disorders and depression) may precede dementia for years, possibly 10 or more, whereas the median duration of follow-up in our study was 6.2 years. We obviously agree but would like to add the following: (i) despite being about 7 years on average, the duration of follow-up was longer in a significant number of subjects, which made it possible to show that the excess risk in exposed subjects was mainly observed after 7 or 8 years, with a stronger trend after 10 years; (ii) in the case-control analysis, a significant association was found for the most distant exposures (starting 8 years or more before dementia) and not for recent ones; (iii) studies conducted on symptoms observed during the prodromal phase of dementia (1) clearly show that their frequency increases when approaching dementia onset. In that respect, if BZD prescription was mainly justified by such prodromes, the association would be expected to be stronger for treatments started a few years before dementia and not the reverse, as shown by our results.

1. Amieva H, Le Goff M, Millet X, Orgogozo JM, Peres K, et al. (2008) Prodromal Alz-heimer's disease: successive emergence of the clinical symptoms. Annals of neurology 64: 492-498.

Competing interests: No competing interests

22 November 2012
Sophie Billioti de Gage
PhD Student
Bernard Bégaud, Antoine Pariente
Université Bordeaux Segalen, INSERM U657
146 rue Léo Saignat, F-33076, Bordeaux cedex, France