Potential population impact of antidepressant use on hip fractures rate in Denmark (DK), Norway (NO) and the Netherlands (NL)

Background: The use of antidepressants has been associated with an increased hip fracture risk in observational studies. However, the potential impact of antidepressant consumption on the population rate of hip fractures has not been estimated. Objectives: To evaluate the population impact of antidepressant use on the rate of hip fractures using publicly accessible drug utilization databases. This study was conducted as part of the IMI PROTECT Study (Drug Utilization). Methods: National consumption data of antidepressants were obtained from publicly accessible databases, including the Danish Medicines Agency (2007), the Dutch Health Care Insurance Board (2009) and the Norwegian Institute of Public Health (2008). In each country, one-year prevalence rates (Pes) were calculated with numbers of antidepressant users and population numbers from public sources. Relative risks (RRs) of a hip fracture after antidepressant exposure versus non-exposure, as previously reported in epidemiological studies, were obtained with a literature search in Pubmed, EMBASE and the Cochrane Library. Pooled RRs were estimated using a random effects model. Together with Pes, population attributable risks (PARs) of antidepressant use to hip fractures were estimated. Results: Relatively small differences in antidepressant consumption were observed between DK (7.4%), NO (6.1%) and the NL (5.8%). Selective serotonin reuptake inhibitors were the most frequently used class of antidepressants in each country (Pes: DK 5.2%, NO 3.7% and NL 3.2%). A 1.7-fold increased hip fracture risk was observed among antidepressant users, as compared to non-users (pooled RR: 1.7; 95% CI 1.5-2.0), based on 11 observational studies (4 cohort, 7 case-control). PAR estimations ranged from 3.9% (95% CI 2.7%-5.4%) in the NL to 4.9% (95% CI 3.4%-6.8%) in DK. Conclusions: These findings suggest that the potential attribution of antidepressant use to the population rate of hip fractures in three different EU countries varies between 4% and 5%