Background: Menopausal (perimenopausal and postmenopausal) women are at higher risk of osteoporotic fractures. Menopausal women may also experience common mental health problems (CMHP) which require the prescribing of selective serotonin re-uptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants. Prescribing of SSRI/SNRI antidepressants may pose an additive risk of osteoporotic fractures.
Objectives: To investigate the association between the prescribing of SSRI/SNRI antidepressants and risk of osteoporotic fractures in menopausal women with CMHPs.
Methods: In this cohort study, primary care records of menopausal women with follow-up between 2000 and 2021 were retrieved from the IMRD-UK database, previously known as THIN. We defined menopausal women as women with a recorded diagnosis of menopause or aged ≥50 years. Our study cohort comprised menopausal women with a CMHP (i.e. depression or generalized anxiety disorder) recorded on or after menopausal onset. Exposure to SSRI/SNRI antidepressants was defined as two new consecutive prescriptions within six months. Start of follow-up was randomly assigned to the unexposed group by incidence density sampling. Osteoporotic fractures were defined as first incident fracture excluding fractures of the skull, face and digits. Incidence rates (IR) were estimated per 1000 person-years-at-risk (PYAR) with 95% confidence intervals (CI). Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Missing data was handled using multiple imputation by chained equations. Relative risk of osteoporotic fractures was estimated by comparing women prescribed SSRI/SNRI antidepressants to those unexposed using a Cox proportional hazards model to estimate hazard ratios (HR) with 95% CI.
Results: We identified 459,431 menopausal women with CMHPs, with 44,582 osteoporotic fractures within a median follow-up of 5.44 (IQR 2.28 -9.99) years. Mean age for participating women was 62.88 years. The risk of osteoporotic fractures was higher in women prescribed SSRI/SNRI antidepressants with an IR of 16.05 (95%CI 15.87-16.23) per 1000 PYAR compared with an IR of 12.43 (95%CI 12.23-12.64) per 1000 PYAR in women without an SSRI/SNRI prescription. We found strong evidence of an association between the prescribing of SSRI/SNRI and risk of osteoporotic fractures (adjusted HR=1.30, 95%CI 1.27-1.32).
Conclusions: In a population of menopausal women with CMHPs, prescribing of SSRI/SNRI antidepressants was associated with a higher risk of osteoporotic fractures. Careful consideration of osteoporosis risk needs to be taken when treating menopausal women with SSRI/SNRI antidepressants.
