Selective serotonin reuptake inhibitors (SSRIs) prevent the development of and reverse pulmonary hypertension (PH) in animal models. We sought to determine whether SSRIs are associated with a decreased incidence of PH in at-risk patients and whether SSRIs are associated with decreased mortality in patients with established PH.
In a case-control study of patients enrolled in the Surveillance of Pulmonary Hypertension in America (SOPHIA) registry, we tested whether patients without PH (no-PH group; n = 155) were more likely to be receiving SSRIs when compared to those with confirmed PH (n = 1,180). In a separate cohort study of adults with documented PH in the referral-based Pulmonary Hypertension Connection (PHC) registry (n = 542), we classified patients into categories by SSRI use, and we examined whether SSRI use was associated with decreased mortality.
In SOPHIA, the confirmed PH group was less likely to be receiving SSRIs compared with the no-PH group (univariate odds ratio [OR], 0.56 [95% confidence interval (CI), 0.39 to 0.82]; p = 0.003; multivariate OR, 0.71l [95% CI, 0.48 to 1.06]; p = 0.09). In the PHC, 69 of 542 patients (13%) were receiving SSRIs at the time of referral. During a mean (± SD) follow-up period of 4.0 ± 3.1 years, 12% of patients receiving SSRIs vs 23% of patients not receiving SSRIs died (hazard ratio [HR], 0.35; 95% CI, 0.14 to 0.87; p = 0.023). The association between SSRI use and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR, 0.35; 95% CI, 0.14 to 0.88; p = 0.026).
SSRIs appear to be associated with a decreased development of PH and a decreased mortality in PH. These findings provide a rationale for clinical trials of SSRIs in PH.