Background Antidepressants may increase the risk of fractures by disrupting sensory-motor function, thereby increasing the risk of falls, and by decreasing bone mineral density and consequently increasing the fall- or impact-related risk of fracture. Selective serotonin reuptake inhibitor (SSRI) antidepressants appear to increase fracture risk relative to no treatment, while less is known about the effect of serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants, despite SNRIs being prescribed with increasing frequency. No prior study has directly examined how fracture risk differs among patients initiating SNRIs versus those initiating SSRIs. Objective The objective of this study was to assess the effect of SNRI vs. SSRI initiation on fracture rates. Data source Data came from a PharMetrics claims database, 1998–2010, which is comprised of commercial health plan information obtained from managed care plans throughout the US. Methods We constructed a cohort of patients aged 50 years or older initiating either of the two drug classes (SSRI, N=335,146; SNRI, N=61,612). Standardized mortality weighting and Cox proportional hazards regression were used to estimate hazard ratios for fractures by antidepressant class. Results In weighted analyses, the fracture rates were approximately equal in SNRI and SSRI initiators: hazard ratios for the first one and five-year periods following initiation were, respectively, 1.11 (95% CI: 0.92–1.36) and 1.06 (95% CI: 0.90–1.26). For the sub-group of patients with depression who initiated on either SNRIs or SSRIs, those initiating SNRIs had a modestly, but not significantly elevated fracture risk, compared with those who initiated on SSRIs, hazard ratio = 1.31 (95% CI: 0.95–1.79). Conclusions We found no evidence that initiating SNRIs rather than SSRIs materially influenced fracture risk among a cohort of middle-aged and older adults.

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