This is a Phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of escitalopram (30 mg/day) in two parallel groups (randomization ratio, escitalopram 2/placebo 1).

Primary objective: to evaluate the efficacy of oral escitalopram at the dosage of 30 mg/day for 16 weeks on the 6-minute walking test in patients with pulmonary hypertension.

Inclusion Criteria:

Subjects who meet all the criteria listed below will be considered for study inclusion:

• Male or female older than 18 years of age

• Meeting World Health Organization (WHO) criteria for pulmonary hypertension (mean pulmonary arterial pressure [PAP] > 25 mmHg at rest and pulmonary capillary wedge pressure < 15 mmHg during right heart catheterization):

  • primary pulmonary hypertension (sporadic or familial), or
  • pulmonary hypertension associated with connective tissue diseases, or
  • pulmonary hypertension associated with HIV infection, or
  • pulmonary hypertension associated with use of appetite suppressants or other toxic compounds, or
  • pulmonary hypertension associated with shunting through a congenital heart defect surgically treated

• Class II or III in the NYHA classification scheme

• With a 6-minute walking test distance between 40% and 80% of theoretical values (approximately 50 and 480 m)

• On conventional treatment, with no change in this treatment during the last month preceding the study. Conventional treatment includes calcium antagonists or beraprost.

• Subject who consents to participate in the study.

Exclusion Criteria:

Subjects with any of the following clinical features will not be included in the study:

• Pulmonary hypertension related to aortic or mitral valve disease, or extrinsic pulmonary vein compression
• Pulmonary hypertension related to hypoxia from respiratory disease with a total lung capacity < 70% or Tiffeneau index < 60% upon testing within the last 6 months (chronic obstructive lung disease, interstitial disease, sleep apnea syndrome, alveolar hypoventilation, chronic exposure to high altitudes, neonatal lung disease, or alveolar capillary dysplasia)
• Pulmonary hypertension associated with portal hypertension
• Pulmonary hypertension secondary to chronic thrombosis and/or embolism (occlusion of the proximal or distal pulmonary arteries by thrombosis)
• In the 6-minute walking test, inability to walk for 6 minutes, for any reason, or walking distance of less than 50 m
• Pregnancy, lactation, women of childbearing potential (if needed, effective contraception will be prescribed)
• History of hypersensitivity to citalopram or to medications structurally related to citalopram
• Treatment with another investigational drug within the 3 months preceding study inclusion
• Cardiovascular, hepatic, neurological or endocrine disease that is clinically significant, or any other significant disease that may interfere with the study protocol or with the interpretation of study findings
• History of drug or alcohol abuse
• Liver failure (except abnormalities related to the right ventricular failure)
• Kidney failure
• Mental status preventing the patient from understanding the nature, objectives, and possible consequences of the study
• Non stabilized psychiatric disorders
• Subject unable to comply with protocol-related constraints (e.g., uncooperative, unable to attend follow-up visits, and probably unable to complete the study).