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Original Research: PULMONARY HYPERTENSION |

Selective Serotonin Reuptake Inhibitors and the Incidence and Outcome of Pulmonary Hypertension

Sanjiv J. Shah, MD; Mardi Gomberg-Maitland, MD, MSc, FCCP; Thenappan Thenappan, MD; Stuart Rich, MD, FCCP
Author and Funding Information

Affiliations: From the Division of Cardiology (Dr. Shah), Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL; and the Section of Cardiology (Drs. Gomberg-Maitland, Thenappan, and Rich), Department of Medicine, University of Chicago, Chicago, IL.

Correspondence to: Stuart Rich, MD, FCCP, Section of Cardiology, University of Chicago Medical Center, 5841 S Maryland Ave, L08, Chicago, IL 60637; e-mail: srich@medicine.bsd.uchicago.edu


Dr. Shah is supported by an Actelion Entelligence Young Investigator Award and an American Heart Association Scientist Development Grant. Dr. Gomberg-Maitland is supported by a Doris Duke Clinical Scientist Development Award.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(3):694-700. doi:10.1378/chest.08-2823
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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.

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