Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension

Kawut, Steven M.; Horn, Evelyn M.; Berekashvili, Ketevan; Lederer, David J.; Widlitz, Allison; Rosenzweig, Erika B.; Barst, Robyn J.

doi:10.1016/j.pupt.2006.01.001

Cited by 58 publications

(39 citation statements)

References 19 publications

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“…The interaction with and uptake of drugs into the pulmonary artery smooth muscle cell by the serotonin transporter may be important, as medications that simply block reuptake of serotonin (selective serotonin reuptake inhibitors) increase local levels of serotonin but have not been associated with PAH in adults (10), do not increase mortality in patients with established PAH (13), and unlike the appetite-suppressant medications, do not promote smooth muscle cell growth in vitro (14). In contrast, maternal use of selective serotonin reuptake inhibitors has been linked to persistent pulmonary hypertension of the newborn; the cause for this discrepancy remains unclear (15).…”

Section: Pah Subgroupsmentioning

confidence: 99%

Pulmonary Arterial Hypertension

Rubin

2006

Proceedings of the American Thoracic Society

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Significant advances in the treatment of pulmonary arterial hypertension (PAH) have occurred over the last 10 years, starting with the approval of epoprostenol in 1998. Subsequently, multiple additional medications have received approval, including a subcutaneous prostacyclin, an inhaled prostacyclin, and oral medications in 2 separate classes. Over this same period, the classification of pulmonary hypertension has been revised with changes including the substitution of the term idiopathic for primary PAH and an expanded list of conditions felt to be associated with the development of PAH. Long-term follow-up studies have provided better information on prognosis and expected outcomes with treatment, with particularly valuable data on reassessment of prognosis after treatment with epoprostenol. Combination therapy is more frequently being used, and limited data on novel therapies such as stem cell transplantation have been published. The purpose of this review is to describe the current state of evidence for the diagnosis, prognosis, and treatment of the patient with PAH. (J Am Coll Cardiol 2008;51:1527-38)

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Section: Pah Subgroupsmentioning

confidence: 99%

Pulmonary Arterial Hypertension

Rubin

2006

Proceedings of the American Thoracic Society

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“…Pousti et al [28] observed decrease in the rate and contractile force of heart in a dose-dependent manner and they suggested that the negative chronotropic and inotropic effect of fluoxetine on isolated guinea-pig atria is probably mediated through an inhibition of the reuptake of adenosine or the A(1) receptor mechanism. Moreover, SSRI were associated with a 50% reduction in the risk of death in a small cohort of pulmonary arterial hypertensive patients [29].…”

Section: Nucleus (N) Z Lines (S) Amplification X 13200 Fig 2 -Elecmentioning

confidence: 93%

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress

Daud

Murad

Meneghini

et al. 2009

Rev Bras Cir Cardiovasc

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“…Our fi ndings are inconsistent with several previous reports. In a single-center, retrospective study of 84 patients with PAH, Kawut and colleagues 18 found that 13 patients with PAH who were exposed to highaffi nity SSRIs showed a tendency toward a reduced risk of death (HR, 0.53; 95% CI, 0.07-3.9; P 5 .53). More recently, using a combined retrospective and prospective database from Chicago that dates back to the 1980s, Shah and colleagues 19 reported that SSRI use conferred a survival advantage in both group I PAH and non-group I PH patients (HR, 0.35; 95% CI, 0.14-0.87; P 5 .023).…”

Section: Unadjusted Outcomes: Mortality and Composite End Pointmentioning

confidence: 99%

“…18,19 However, maternal SSRI use has been identifi ed as a potential risk factor for the development of persistent PH of the newborn, raising the possibility that SSRI exposure may actually be harmful to human pulmonary vascular development. 20 Furthermore, a more recent population-based study in Canada reported a positive association between SSRI use and PAH, which was ascribed to residual confounding.…”

Section: Comorbid Conditionsmentioning

confidence: 99%

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Pulmonary Arterial Hypertension

Sadoughi

Roberts

Preston

et al. 2013

Chest

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531T he serotonin hypothesis of pulmonary arterial hypertension (PAH) emerged . 40 years ago and was reemphasized in the 1990s following the association of pulmonary hypertension (PH) 1 with anorexic agents such as aminorex fumarate and fenfl uramine. [2][3][4][5] Serotonin promotes pulmonary arterial smooth muscle cell and fi broblast proliferation, pulmonary arterial vasoconstriction, and local microthrombosis-all key pathogenic features in PAH. These effects of serotonin are mediated by interactions between serotonin and its transporter and receptors. [6][7][8][9][10] In particular, the serotonin transporter (SERT) plays a key role in the pathogenesis of experimental PH; in animal models, SERT overexpression predisposes to the development of PH, whereas pharmacologic blockade of SERT is protective. 1,[11][12][13][14] In humans, a functional polymorphism in the SERT gene correlates with more severe PH associated with COPD. 15 Selective serotonin reuptake inhibitors (SSRIs) act via blockade of SERT, resulting in an extracellular accumulation of serotonin and increased activation of serotonin receptors. 16 SSRIs have been associated with both protection against and regression of PH in animal models, suggesting a possible role in the treatment of PAH in humans. 1,14,17 Early observational studies have suggested therapeutic effi cacy of SSRIs in patients with Background: Selective serotonin reuptake inhibitors (SSRIs) have been suggested to offer therapeutic benefi t in patients with pulmonary arterial hypertension (PAH). We conducted two analyses to explore the association between SSRI use and PAH outcomes using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry). Methods: First, new users (SSRI-naive patients who initiated treatment after enrollment, incident use analysis, n 5 220) were matched (1:2) with non-SSRI users (nonusers, n 5 440) by enrollment center, sex, date of most recent visit, age, and 6-min walk distance. Second, a cross-sectional design was used to compare nonusers (n 5 2,463), high-affi nity SSRI users (n 5 430), and non-high-affi nity SSRI users (n 5 125) at enrollment. Mortality and a composite end point defi ned by events indicative of clinical worsening were evaluated. Results: New users had a higher risk of death (unadjusted hazard ratio [HR], 1.74; 95% CI, 1.19-2.54; P 5 .004) and were less likely to be free from the composite end point 2 years after enrollment vs nonusers (25.7% vs 43.2%, respectively; P , .001). Similarly, among prevalent SSRI users (patients with a history of SSRI use at enrollment), high-affi nity SSRI users were less likely to be free from the composite end point vs nonusers (unadjusted HR, 1.20; 95% CI, 1.07-1.36; P 5 .003). In both analyses, differences in outcome were maintained after adjustment for clinical variables previously associated with PAH outcomes. Conclusions:In a large population of patients with PAH, incident SSRI use was associated with increased mortality and a greater risk of clinical worsening, although we could ...

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Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension

Cited by 58 publications

References 19 publications

Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Pulmonary Arterial Hypertension

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