Comparing Stroke Risk in Patients Treated with Selective Serotonin Reuptake Inhibitors (SSRIs) versus Non-SSRI Antidepressants: A retrospective cohort study and meta-analysis

AimsDespite the presence of studies indicating a potential elevated risk of stroke associated with selective serotonin reuptake inhibitors (SSRIs), current evidence is inconclusive. This study aims to evaluate the stroke risk associated with SSRI use using non-SSRI antidepressants as comparator through retrospective cohort study and meta-analysis of observational studies. MethodsWe extracted data from a territory-wide public healthcare database in Hong Kong to conduct a retrospective cohort study of patients aged 18+ years who started on SSRI or non-SSRI antidepressants between January 2018 to April 2024. Poisson regression with robust variance estimation was conducted to estimate the incidence rate ratio of stroke in SSRI users using non-SSRI users as active comparator. We subsequently conducted a systematic review and meta-analysis based on the current cohort study and all existing published observational data. Quality of studies was assessed using the Newcastle-Ottawa Scale. Results122,679 individuals were included in the cohort study, among which 55,279 were SSRI users. SSRI users had an adjusted HR of 0.95 (95% CI 0.77-1.20) for stroke compared to non-SSRI users, suggesting a non-significant lower risk of stroke. Findings were consistent across subgroups by stroke types (i.e. ischemic stroke and hemorrhagic stroke). The result of our cohort study was aggregated with 5 other observational studies, and a pooled estimates of RRs were extracted (RR 0.93, 95% CI 0.81-1.07). ConclusionOur findings suggested that compared with non-SSRI antidepressants, SSRIs are not associated with a higher risk of stroke based on all available observational data.