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



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.



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.



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.



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.
Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, 39 Avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France. isabelle.carriere@inserm.fr.|University of Montpellier, U1061, Montpellier, France. isabelle.carriere@inserm.fr.
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Carrière
Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, 39 Avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France.|University of Montpellier, U1061, Montpellier, France.
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Farré
Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, 39 Avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France.|University of Montpellier, U1061, Montpellier, France.
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Norton
Department of Psychiatry, CHU Caremeau, Nîmes, France.
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Wyart
Inserm, ISPED, Centre U1219 - Bordeaux Population Health Research Center, Bordeaux, France.|University of Bordeaux, ISPED, Centre U1219, Bordeaux, France.
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Tzourio
Inserm, ISPED, Centre U1219 - Bordeaux Population Health Research Center, Bordeaux, France.|Department of Clinical Pharmacology, CHU Bordeaux, Bordeaux, France.
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Noize
Inserm, ISPED, Centre U1219 - Bordeaux Population Health Research Center, Bordeaux, France.|University of Bordeaux, ISPED, Centre U1219, Bordeaux, France.
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Pérès
Inserm, ISPED, Centre U1219 - Bordeaux Population Health Research Center, Bordeaux, France.|Department of Clinical Pharmacology, CHU Bordeaux, Bordeaux, France.
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Fourrier-Réglat
Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, 39 Avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France.|University of Montpellier, U1061, Montpellier, France.
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Ancelin
D000058:Accidental Falls; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors
Antidepressants; Elderly; Falls; Fractures