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Trajectories of Benzodiazepine Use among Older Adults from a Concordance-with-Guidelines Perspective: A Nationwide Cohort Study

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Abstract

Background and Objective

Benzodiazepines (including zolpidem and zopiclone) are often associated with higher-than-recommended intake and durations of use, especially in older adults. The objective of this study was to characterize trajectories of benzodiazepine use according to recommended patterns in older adults, and to assess predictors of the risk of developing each of these trajectories.

Methods

Using the French Health Insurance database, we constituted a cohort of adults aged ≥ 65 years who initiated benzodiazepines in 2007 and were followed for up to 8 years. Concordance with benzodiazepine use guidelines was assessed on a quarterly basis according to a “concordance-with-guideline score” with values 1–5. Group-based trajectory modeling was then applied as implemented in the Proc Traj procedure in SAS to define guideline-concordant trajectories based on seven baseline patient-centered characteristics: sex, complementary health insurance coverage, treated alcohol and tobacco use disorder, polypharmacy, hospital stay, and registered chronic diseases.

Results

Among 5080 new users (64.1% women, median age 74 years), six trajectories of benzodiazepine use were identified. Three, representing 70% of users, were concordant with guidelines, whereas three implied non-concordant benzodiazepine use for part or all of the benzodiazepine use follow-up. Polymedicated patients were more prone to develop chronic non-guideline-concordant initially guideline-concordant use, whereas those with a history of long-term disease and hospitalization were more likely to develop chronic non-guideline-concordant use. The number of prescribers during the first quarter, number of daily defined doses, use of loperamide, and use of psychostimulants were associated with a higher risk of developing an initial and persistent non-guideline-concordant use. Treatment initiation by a psychiatrist, initial use of World Health Organization (WHO) step-2 opioids and non-benzodiazepine anxiolytics or sedatives were associated with a higher risk of late non-guideline-concordant use.

Conclusions

Concordance with guidelines varied over time during benzodiazepine use in older adults. A third of these adults will hypothetically follow one of the identified non-guideline-concordant trajectories, consisting of initial and/or late non-guideline concordance. This was associated with modifiable and nonmodifiable factors that clinicians should be aware of for tailoring the monitoring of patients.

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Acknowledgements

We thank the editor and anonymous reviewers whose careful reading allowed improving the quality of the manuscript. We thank Dr. Sophie Billioti de Gage (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) for her collaboration in developing in-house algorithms for alcohol and tobacco dependence treatment identification.

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Authors and Affiliations

  1. University of Bordeaux, Inserm, Bordeaux Population Health Research Center Team Pharmacoepidemiology, Team AHeaD, UMR 1219, 33000, Bordeaux, France

    Sandy Maumus-Robert, Ana Jarne-Munoz, Marie Tournier, Bernard Bégaud & Antoine Pariente

  2. Drugs Systematized Assessment in real-liFe EnviRonment (DRUGS-SAFEr) Pharmacoepidemiology Center, Bordeaux, France

    Sandy Maumus-Robert, Ana Jarne-Munoz, Marie Tournier & Antoine Pariente

  3. Hopital Charles Perrens, Bordeaux, France

    Marie Tournier

  4. Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie médicale, 33000, Bordeaux, France

    Antoine Pariente

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Corresponding author

Correspondence to Antoine Pariente.

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Funding

This work was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) (Grant number 2019S015), in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The present study is part of the Drugs Systematized Assessment in real-liFe EnviRonment (DRUGS-SAFER) research program. This program aims at providing an integrated system allowing the concomitant monitoring of drug use and safety in France. The potential impact of drugs, frailty of populations and seriousness of risks drive the research program. The French Medicines Agency played no role in the study design, conduct, and interpretation of results or discussion. This publication represents the views of the authors and does not necessarily represent the opinion of the French Medicines Agency.

Conflicts of interest

The authors declare they have no conflict of interest.

Ethics approval

By agreement of the French Data Protection Supervisory Authority, neither ethics committee approval nor informed consent were required for this observational study based on medico-administrative databases because of the anonymous nature of the data.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material/code availability

No additional data available by author (French law to access SNDS https://www.snds.gouv.fr). The SAS code used is available from the corresponding author, antoine.pariente@u-bordeaux.fr, upon request.

Authors’ contributions

Conception or design of the work: SMR, AJM, MT, BB, AP; data acquisition and analysis: AJM; data interpretation: SMR, AJM, MT, BB, AP; manuscript drafting: SMR, AJM, AP; manuscript critical reviewing: SMR, AJM, MT, BB, AP; final approval of the version to be published: SMR, AJM, MT, BB, AP; administrative, technical, or material support: SMR, AJM; study supervision: AP. All the authors have read and approved the final submitted manuscript, and agree to be accountable for the work.

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Maumus-Robert, S., Jarne-Munoz, A., Tournier, M. et al. Trajectories of Benzodiazepine Use among Older Adults from a Concordance-with-Guidelines Perspective: A Nationwide Cohort Study. Drugs Aging 40, 919–931 (2023). https://doi.org/10.1007/s40266-023-01057-x

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