Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: A systematic review and meta-analysis

Objective: To evaluate the association between selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) use and risk of fractures in older adults. Methods: We systematically identified and analyzed observational studies comparing SSRI/SNRI use for depression with non-SSRI/SNRI use with a primary outcome of risk of fractures in older adults. We searched for studies in MEDLINE, PsycINFO, Embase, DARE (Database of Abstracts or Reviews of Effects), the Cochrane Library, and Web of Science clinical trial research registers from 2011 for SSRIs and 1990 for SNRIs to November 29, 2016. Results: Thirty-three studies met our inclusion criteria; 23 studies were included in meta-analysis: 9 case-control studies and 14 cohort studies. A 1.67-fold increase in the risk of fracture for SSRI users compared with nonusers was observed (relative risk 1.67, 95% CI 1.56-1.79, P=.000). The risk of fracture increases with their long-term use: within 1 year, the risk is 2.9% or 1 additional fracture in every 85 users; within 5 years, the risk is 13.4% or 1 additional fracture in every 19 users. In meta-regression, we found that the increase in risk did not differ across age groups (odds ratio = 1.006; P=.173). A limited number of studies on SNRI use and the risk of fractures prevented us from conducting a meta-analysis. Conclusions: Our systematic review showed an association between risk of fracture and the use of SSR1s, especially with increasing use. Age does not increase this risk. No such conclusions can be drawn about the effect of SNRIs on the risk of fracture because of a lack of studies.