Risk of osteoporotic fractures in menopausal women with common mental health diagnoses prescribed SSRIs/SNRIs: cohort and self-controlled case series analyses

In a population-based cohort study of menopausal women with common mental health diagnoses, SSRIs/SNRIs were associated with a 32% increased risk of osteoporotic fractures. The risk of osteoporotic fractures was particularly increased for longer periods of treatment with SSRIs/SNRIs (> 5 years) and in younger menopausal women (< 50 years old). PURPOSE: To investigate the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of osteoporotic fractures (OF) in menopausal women with common mental health diagnoses (CMHD). METHODS: We conducted the study with two designs (cohort and self-controlled case series [SCCS]), using the IQVIA Medical Research Database (IMRD) UK. The source population comprised women aged ≥ 50 years and women with a record indicating menopause (< 50 years). All women had a recorded CMHD. For the cohort analysis, the risk of OFs was estimated by comparing women prescribed SSRIs/SNRIs (exposed) to those not exposed. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). For the SCCS, women acted as their own controls; periods of exposure to SSRIs/SNRIs were compared to periods of non-exposure using conditional Poisson regression to estimate incidence rate ratios (IRR) with 95% CIs. RESULTS: We identified 292,848 women, of whom 35,222 experienced OFs within a median follow-up of 6.01 years. We found strong evidence of an association between SSRIs/SNRIs and the risk of OFs (adjusted HR = 1.32, 95% CI:1.29-1.35). Compared to periods of no exposure, SSRIs/SNRIs increased the risk of OFs during the first 30 days (IRR = 1.38, 95% CI:1.26-1.51), during the first 90 days (IRR = 1.58, 95% CI: 1.48-1.69), and the remaining exposure (IRR = 1.42, 95% CI:1.37-1.48). CONCLUSIONS: In a population of menopausal women with CMHDs, the prescribing of SSRIs/SNRIs antidepressants was associated with a higher risk of OFs. Careful assessment of osteoporosis risk needs to be considered when treating menopausal women with SSRIs/SNRIs antidepressants.