Abstract
Introduction: The serotonergic pathway appears to be involved in pulmonary hypertension (PH) and selective serotonin reuptake inhibitors (SSRIs) prevent development of PH in animal models. We hypothesized that SSRIs would decrease development of PH and would be associated with decreased mortality in PH patients (pts). Methods: In a case-control study of the Surveillance of PH in America (SOPHIA) registry, we first tested whether pts without PH had increased SSRI exposure compared to those with PH. In SOPHIA, 1335 pts underwent invasive hemodynamic study and were classified as no-PH (N=155) or confirmed-PH (N=1180). We used logistic regression to see if the no-PH group had increased exposure to SSRIs. Next, we studied baseline SSRI use in the Pulmonary Hypertension Connections (PHC) cohort, a referral-based registry of adults with PH (N=542). A Cox proportional hazards analysis was used to see if SSRI use was associated with decreased mortality. Results: In SOPHIA, the no-PH group had a 1.8-fold increased odds of being exposed to SSRIs compared to the confirmed-PH group (p<0.05). In PHC, 69/542 (13%) were taking SSRIs at time of referral. Pts taking SSRIs were more often obese, but otherwise had similar to those not taking SSRIs. During mean follow-up of 4.0±3.1 yrs, 12% of pts taking SSRI vs. 23% of pts not taking SSRI died (hazard ratio [HR] 0.35; p=0.023). The association between SSRI and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR 0.36; p=0.026). Conclusions: SSRI use appears to be associated with decreased development of PH and decreased mortality in PH. These findings provide rationale for a randomized trial of SSRIs in PH.
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