Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older
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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.
The objective of this study was to assess the effect of SNRI versus SSRI initiation on fracture rates.
Data were derived from a PharMetrics claims database, 1998–2010, which is comprised of commercial health plan information obtained from managed care plans throughout the US.
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 (HRs) for fractures by antidepressant class.
In weighted analyses, the fracture rates were approximately equal in SNRI and SSRI initiators: HRs for the first 1- and 5-year periods following initiation were 1.11 [95 % confidence interval (CI) 0.92–1.36] and 1.06 (95 % CI 0.90–1.26), respectively. For the subgroup 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 [HR 1.31 (95 % CI 0.95–1.79)].
We found no evidence that initiating SNRIs rather than SSRIs materially influenced fracture risk among a cohort of middle-aged and older adults.
KeywordsFracture Risk Selective Serotonin Reuptake Inhibitor Norepinephrine Reuptake Inhibitor Depression Diagnosis Decrease Bone Mineral Density
Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R01 MH085021. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Stürmer receives investigator-initiated research funding and support as Principal Investigator (R01 AG023178) and Co-Investigator (R01 AG042845) from the National Institute on Aging, and as Co-Investigator (R01 CA174453) from the National Cancer Institute at the National Institutes of Health, and also as Principal Investigator of a Pilot Project from the Patient-Centered Outcomes Research Institute (PCORI). Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company, although he receives salary support from the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck) and research support from pharmaceutical companies (Amgen, Merck) to the Department of Epidemiology, University of North Carolina at Chapel Hill. Drs. Miller, Sheu, Azrael, and Swanson, as well as Ms. Lanteigne and Ms. Pate, have no conflicts of interest.
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