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Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort

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Abstract

Summary

In this population-based elderly cohort, participants using selective serotonin reuptake inhibitor (SSRI) antidepressants have an increased risk of falls and fractures notably when the treatment was continued over 4 years. Among the various SSRI types, citalopram only was at significant risk for falls and fluoxetine for fractures.

Introduction

Increased risk of falls and fractures has been reported in elderly users of SSRIs. However, biases were insufficiently addressed notably temporality between exposure and outcome and confounding by residual depression. Our objective was to examine the associations between SSRIs and fall or fracture incidence focusing on their chronic use and different types of SSRIs.

Methods

The population-based cohort included participants aged 65 years and above, who had not fallen before inclusion (n = 6599) or were free of recent fracture (n = 6823) and were followed up twice over 4 years. New fall and fracture events were self-reported and defined as at least two falls and one fracture, respectively, during the previous 2 years. SSRI users were compared with those taking no antidepressants. Hazard ratios (HRs) were estimated using Cox models with delayed entry and adjusted for many confounders including residual depressive symptoms.

Results

Incidence of falls was 19.3 % over 4 years and that of fractures 9.5 %. After multi-adjustment, SSRI intake was significantly associated with a higher risk of falls (HR, 95 % CI = 1.58, 1.23–2.03) and fractures (HR, 95 % CI = 1.61, 1.16–2.24). The risks were significantly increased by 80 % in those continuing the treatment over 4 years. Citalopram intake only was at significant risk for falls and fluoxetine for fractures.

Conclusions

In this large community-dwelling elderly sample, SSRI users were at higher risk of falls and fractures. This association was not due to reverse causality or residual depressive symptoms. Different SSRI drugs may have specific adverse effects on falls and fractures.

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Acknowledgments

The 3C Study is conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (Inserm), Victor-Segalen Bordeaux II University, and Sanofi-Aventis. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, the Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon, the Fondation de France, the Ministry of Research-Inserm Programme “Cohorts and collection of biological material,” Novartis, and the Fondation Plan Alzheimer.

This work was supported by the Fondation pour la Recherche Médicale under the program “Iatrogénie des Médicaments,” project “ELIANE-DEP – IMD20131229108.”

Sponsor’s role

The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, 39 Avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France

    I. Carrière, A. Farré, J. Norton & M. L. Ancelin

  2. University of Montpellier, U1061, Montpellier, France

    I. Carrière, A. Farré, J. Norton & M. L. Ancelin

  3. Department of Psychiatry, CHU Caremeau, Nîmes, France

    M. Wyart

  4. Inserm, ISPED, Centre U1219 - Bordeaux Population Health Research Center, Bordeaux, France

    C. Tzourio, P. Noize, K. Pérès & A. Fourrier-Réglat

  5. University of Bordeaux, ISPED, Centre U1219, Bordeaux, France

    C. Tzourio & K. Pérès

  6. Department of Clinical Pharmacology, CHU Bordeaux, Bordeaux, France

    P. Noize & A. Fourrier-Réglat

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  1. I. Carrière
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  2. A. Farré
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  3. J. Norton
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  4. M. Wyart
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  5. C. Tzourio
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  6. P. Noize
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  7. K. Pérès
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  8. A. Fourrier-Réglat
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  9. M. L. Ancelin
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Correspondence to I. Carrière.

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The study protocol was approved by the Ethical Committee of the Bicêtre University-Hospital (France) and written informed consent was obtained from each participant.

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Carrière, I., Farré, A., Norton, J. et al. Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort. Osteoporos Int 27, 3187–3195 (2016). https://doi.org/10.1007/s00198-016-3667-7

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