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Benzodiazepine Use and Risk of Developing Alzheimer’s Disease: A Case-Control Study Based on Swiss Claims Data

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Abstract

Background

A possible association between benzodiazepine use and Alzheimer’s disease (AD) has been hypothesized in previous studies.

Objectives

Using claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between previous benzodiazepine use and the risk of AD.

Methods

We conducted a matched case-control study and identified 1438 incident AD cases between 2013 and 2014 based on recorded first-time use of drugs used to treat AD [i.e., acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-d-aspartate receptor antagonist memantine] and matched one control to each case on age, sex, index date, and residence (canton). Because the initiation of benzodiazepine use shortly before the AD diagnosis date may occur as a result of symptomatic treatment of prodromal symptoms of early major neurocognitive disorder, we introduced an induction period of 2 years before the AD diagnosis date. Additionally, we categorized medication use by duration of use prior to the index date using prescriptions. We applied conditional logistic regression analyses to calculate odds ratios with 95% confidence intervals and adjusted for use of antidepressants.

Results

The crude odds ratio (95% confidence interval) of developing AD for patients starting benzodiazepine treatment was 1.71 (1.17–2.99) in the year before diagnosis and 1.19 (0.82–1.72) in the third year before diagnosis. After accounting for benzodiazepine use initiated during the prodromal phase, benzodiazepine use was not associated with an increased risk of developing AD; long-term benzodiazepine use (≥30 prescriptions) yielded an adjusted odds ratio of 0.78 (0.53–1.14).

Conclusions

After taking into consideration a possible protopathic bias in the 2 years preceding the AD diagnosis date, benzodiazepine use was not associated with an increased risk of developing AD.

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Acknowledgements

This work was supported by the Department of Health Sciences, Helsana Group, Zurich, Switzerland. The authors thank Mathias Frueh for computer programming.

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Authors and Affiliations

  1. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, Hospital Pharmacy, University of Basel, Spitalstrasse 26, 4031, Basel, Switzerland

    Fabienne A. Biétry & Christoph R. Meier

  2. Hospital Pharmacy, University Hospital Basel, Basel, Switzerland

    Fabienne A. Biétry & Christoph R. Meier

  3. Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland

    Alena M. Pfeil & Matthias Schwenkglenks

  4. Department of Health Sciences, Helsana Insurance Group, Zürich, Switzerland

    Oliver Reich

Authors
  1. Fabienne A. Biétry
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  2. Alena M. Pfeil
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  3. Oliver Reich
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  4. Matthias Schwenkglenks
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  5. Christoph R. Meier
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Corresponding author

Correspondence to Christoph R. Meier.

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Funding

The project was partially funded by the Helsana Group, Switzerland.

Conflict of interest

All authors meet the International Committee of Medical Journal Editors requirements for authorship, and each author confirms that the manuscript represents honest and original work. All versions of the manuscript were reviewed and approved by all authors. The data have partially been reported in a document in German in Switzerland produced by the Helsana Group (‘Helsana Arzneimittelreport’). The authors have no conflicts of interest to declare.

Author Contributions

Biétry FA: Study conception and design, statistical analysis and interpretation of data, drafting the manuscript. Pfeil AM: Study conception and design, statistical analysis. Reich O: Editing the manuscript. Schwenkglenks M: Study conception and design, editing the manuscript. Meier CR: Study conception and design, acquisition of data, analysis and interpretation of data, editing the manuscript.

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Biétry, F.A., Pfeil, A.M., Reich, O. et al. Benzodiazepine Use and Risk of Developing Alzheimer’s Disease: A Case-Control Study Based on Swiss Claims Data. CNS Drugs 31, 245–251 (2017). https://doi.org/10.1007/s40263-016-0404-x

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  • DOI: https://doi.org/10.1007/s40263-016-0404-x

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