Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

Inclusion Criteria: 1. WHO Group I PAH subtypes of idiopathic PAH and PAH associated with drugs / toxins, connective tissue disease, repaired congenital heart disease and unrepaired atrial septal defect 2. Age 16-80 3. WHO Functional Class II or III 4. Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤ 15 mmHg, and PVR ≥ 3 Wood units. 5. Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing potential) 6. One or more approved PAH therapies for ≥ 3 months, no change in dose for 1 month (endothelin-1 antagonist, phosphodiesterase-5 inhibitor, prostacyclin / prostacyclin analog). Novel approved therapies in one of the three existing classes will also be acceptable as background therapy if they become available during the course of the study; other medication classes are excluded Exclusion Criteria: 7. WHO Functional Class IV or listed for lung transplant 8. Moderate or greater obstructive lung disease: FEV1/FVC \<70% and FEV1 \<60% 9. Moderate or greater restrictive lung disease: TLC or FVC \<60% (if 50-60%: OK if TLC or FVC ≥50% + PFT stable x1 year + CT with no more than mild lung disease) 10. Other cause for pulmonary hypertension: all other WHO group I diseases (including but not limited to liver disease, HIV), and WHO Groups II-V (i.e. left heart disease, lung disease, chronic PE and miscellaneous causes)24. 1. High probability VQ or positive CTA 2. Left ventricular ejection fraction \<40% 11. Depression 12. Severe liver, renal or other medical or physical disease preventing completion of the study procedures 13. Use of antidepressants within 3 months