Association Between Antidepressant Drug Use and Hip Fracture in Older People Before and After Treatment Initiation

Abstract

Importance: Treatment with antidepressants has been associated with hip fracture. This association could restrict the treatment options, especially in older patients.

Objective: To investigate the association between antidepressant drug treatment and hip fracture starting 1 year before the initiation of treatment.

Design, setting, and participants: In this nationwide cohort study, 204 072 individuals in the Prescribed Drugs Register of Sweden's National Board of Health and Welfare aged 65 years or older who had a prescription of antidepressants filled between July 1, 2006, and December 31, 2011, were matched by birth year and sex to 1 control participant who was not prescribed antidepressants (for a total of 408 144 people in the register). Outcome data were collected from 1 year before to 1 year after the index date (date of prescription being filled). Data analysis was performed from July 1, 2005, to December 31, 2012.

Exposures: First filled prescription of an antidepressant drug.

Main outcomes and measures: Incident hip fractures occurring in the year before and year after initiation of antidepressant therapy were registered. Associations were investigated using multivariable conditional logistic regression models and flexible parametric models.

Results: Of the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.

Conclusions and relevance: The present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.

Figure.. Associations Between Antidepressant Drug Treatment Initiation and Hip Fracture

Flexible parametric models for all participants and all antidepressants before (A) and after (B) treatment initiation. Nonusers of antidepressants are the reference in the analyses. Conditional analyses were performed using 3 df and knots at default positions. The gray area represents the 95% CI. Participants who had a hip fracture, died, or stopped filling their prescription were censored from the analysis.