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

Objective: to evaluate the association between SSRI and 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, the Cochrane Library, Web of Science clinical trials 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 to non-users was observed (Relative Risk 1.67, 95% CI 1.56-1.79, p=0.000). The risk of fracture increases with their long-term use: within 1 year the risk is 2.9% or one additional fracture in every 85 users; within 5 years the risk is 13.4% or one additional fracture in every 19 users. In meta-regression we found that the increase in risk did not differ across age groups (OR=1.006; p=0.173). A limited number of studies on SNRIs 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 SSRIs, 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 due to a lack of studies.