Hypertension associated with serotonin reuptake inhibitors: A new analysis in the WHO pharmacovigilance database and examination of dose-dependency

Introduction: Recent literature has reported instances of drug associated with hypertension with serotonin reuptake inhibitors (SRIs). Nonetheless, the association between SRIs and hypertension development is the subject of ongoing debate. It remains uncertain whether this is indicative of a class effect, and if dose-effect exist. To investigate the potential class effect associating SRIs with hypertension reporting, we utilized real-world data from VigiBase®, the World Health Organization (WHO) pharmacovigilance database. Methods: We conducted an updated disproportionality analysis within VigiBase® to identify a signal of hypertension reporting with individual SRIs by calculating adjusted reporting odds ratios (aRORs) within a multivariate case/non-case study design. Additionally, we explored the presence of a dose-effect relationship. Results: The database contained 13,682 reports of SRI associated with hypertension (2.2%), predominantly in women (70.0%). Hypertension was most reported in the 45-64 years old age group (44.8%). A total of 3,879 cases were associated with sertraline, 2,862 with fluoxetine, 2,516 with citalopram, 2,586 with escitalopram, 2,441 with paroxetine, 201 with fluvoxamine and 8 with zimeldine. A significant ROR was observed for all SRIs in both univariate (RORs ranging from 1.39 to 1.54) and multivariable analyses (aRORs ranging from 1.16 to 1.40) after adjustments for age group, sex, concurrent antihypertensive medication and drugs knowns to induce hypertension, except for fluvoxamine and zimeldine. No dose-response relationship was identified. Conclusion: This investigation, conducted under real life conditions, unveils a notable pharmacovigilance safety signal associating SRI usage with hypertension reporting. No dose-response effect was detectable. Further longitudinal studies are warranted.