Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension

Background: 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. Methods: 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. Results: 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). Conclusions: 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.