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

Abstract

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.

Negative effect of serotonin–norepinephrine reuptake inhibitor therapy on rat bone tissue after orchidectomy

“…The mechanism of action of different classes of antidepressants appears to produce different skeletal effects: several rodent and human observational studies have reported negative skeletal effects with serotonergic antidepressants. There have been several recent studies linking SSRI/SNRI drugs to increased fragility in humans, which are consistent with our results (Warden et al, 2010(Warden et al, , 2008Bonnet et al, 2007;Lanteigne et al 2015;Moura et al, 2014).…”

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

“…No relevant randomized controlled studies were found. Sixteen studies were included from the previous systematic review, and 17 studies were identified as new in the databases (Figure ) …”

“…The studies we found were published between 1998 and 2016, with 11 studies since 2013 . Two studies were reported across multiple articles and each was treated as a single distinct study: Vestergaard et al and Souverein et al One study reported results from both a cohort and a nested case‐control analysis .…”

“…Six studies examined fracture incidence relative to SSRI daily dose (DDD) and 3 studies relative to affinity for 5‐HTT . Two studies reported the outcome for different follow‐up periods …”

Clinical Factors, Disease Parameters, and Molecular Therapies Affecting Osseointegration of Orthopedic Implants

“…Antidepressants, and particularly selective serotonin reuptake inhibitors (SSRI), can have negative effects on the bone and increase the risk of fractures 122,123 . Depression is also one of the strongest risk factors for revision in arthroplasty patients 72 .…”