Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension

Background: Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance which leads to right ventricular failure. Serotonin and the scrotonin transporter play an important role in animal and human studies of PAH. We therefore hypothesized that PAH patients treated with high-affinity selective scrotonin reuptake inhibitors (SSRIs) would have a reduced risk of death compared to PAH patients not treated with SSRIs. Methods: We performed a retrospective cohort study of 84 consecutive adult PAH patients who underwent initial evaluation from January 1994 to June 2002 at the Pulmonary Hypertension Center of the New York Presbyterian Hospital. Patient-time while receiving high-affinity SSRls (K-d < 1 nmol) (paroxetine, sertraline, or fluoxetine) was considered exposed. Patient-time while receiving tricyclic, atypical, or no antidepressants was considered unexposed. Results: Thirteen of the 84 patients (15%) used high-affinity SSRls during the study period. Five patients were taking high-affinity SSRls at baseline and 8 initiated high-affinity SSRIs during the follow-up period. The median time from baseline evaluation until initiation of high-affinity SSRls was 125 (0-1227) days. The median duration of high-affinity SSRI use was 482 (110-1624) days and the total at-risk time on high-affinity SSRls was 18.1 person-years. Seventy-nine (94%) patients were treated with warfarin; 38 (45%) received continuous intravenous epoprostenol; 12 (14%) received continuous subcutaneous treprostinil, and 23 (27%) were treated with oral bosentan. The median follow-up was 764 days. Twenty-four patients died and one underwent lung transplantation during the study period. There were no differences in age, gender, diagnosis, hemodynamics, or incidence of acute vasoreactivity between SSRI users and nonusers. The risk of death for high-affinity SSR1 users was lower but not statistically significantly different from that of non-users (hazard ratio = 0.53, 95% CI 0.07 to 3.9, p = 0.53). Adjustment for demographics, diagnosis, hemodynamics, or other therapies did not significantly change this result. Conclusions: SSR1 use was associated with a 50% reduction in the risk of death in a cohort of PAH patients which was not statistically significant. Larger cohort studies may better define this relationship; an adequately powered trial of high-affinity SSRls in PAH patients may be warranted. (c) 2006 Elsevier Ltd. All rights reserved.