Hypertension induced by serotonin reuptake inhibitors: analysis of two pharmacovigilance databases

Drug‐induced hypertension was described with several pharmacological classes, especially with serotonin reuptake inhibitors ( SRI s). However, this link has remained controversial: the French summary of product characteristics specify a risk of hypertension only with paroxetine and sertraline. To identify a possible class effect common to all SRI s, our study investigated the reports of hypertension associated with SRI s in two pharmacovigilance databases. Two different types of investigations were performed: (i) a comparative study in VigiBase ® , which is the World Health Organization ( WHO ) pharmacovigilance database ( PVDB ), from where notifications of hypertension with six SRI s (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were extracted. The relationship between the suspected SRI s and the occurrence of hypertension was assessed by calculating reporting odds ratio ( ROR ) in a case/non‐case design; (ii) a descriptive study of hypertension reports associated with SRI s in the French pharmacovigilance database ( FPVDB ). In VigiBase ® , 14 824 notifications of SRI ‐induced hypertension (2.5%) were identified (mean age 54.3 years, mainly women 69.1%). Among them, 3 879 (26.2%) were associated to sertraline; 3 118 (21.0%) to fluoxetine; 2 725 (18.4%) to paroxetine; 2 570 (17.3%) to citalopram; 2 295 (15.5%) to escitalopram; and 237 (1.6%) to fluvoxamine. A significant ROR value was found with all six SRI s ( ROR range from 1.16 to 1.92). In the FPVDB , 24 reports of hypertension were found with all six SRI s used at standard doses, mainly in women (66.7%) with a mean age of 57.8 years and a median time of onset of 6 days. In 10 cases (42%), patients had a history of hypertension. This study, performed in real conditions of life, shows a significant pharmacovigilance safety signal between the use of SRI s and the development or worsening of hypertension.