Selective serotonin reuptake inhibitors SSRIs have been suggested to offer therapeutic benefit in patients with pulmonary arterial hypertension PAH. Mortality and a composite end point defined by events indicative of clinical worsening were evaluated. New users had a higher risk of death unadjusted hazard Paxil and pulmonary hypertension in adults [HR], 1. Paxil and pulmonary hypertension in adults both analyses, differences in outcome were maintained after adjustment for clinical variables previously associated with PAH outcomes.
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 not adjust for all potential confounders.
These effects of serotonin are mediated by interactions between serotonin and its transporter and receptors.
Selective serotonin reuptake inhibitors SSRIs act via blockade of SERT, resulting in an extracellular accumulation of serotonin and increased activation of serotonin receptors. The registry design and baseline characteristics of the enrolled patients have been described previously.
To detect an association between Paxil and pulmonary hypertension in adults use and clinical outcomes, we applied two analytical approaches. In the second approach prevalent use analysisa cross-sectional design was used.
In this analysis, SSRI use at the time of enrollment served to classify patients into one of three groups: Two outcome variables were assessed: Kaplan-Meier estimates and Cox proportional hazards models were used for the outcome analyses. Among those reporting a history of drug or toxin exposure, anorexigens fenfluramine and its derivatives or amphetamines were the most common agents used 2.
The prevalent use analysis comprised patients who started Paxil and pulmonary hypertension in adults at time of enrollment. Data are presented as No. The prevalence of comorbid conditions was similar with the exception of obstructive airway disease between Paxil and pulmonary hypertension in adults users and nonusers in the incident use analysis Table 1. As expected, SSRI users had a higher proportion of patients with depression than nonusers in both analyses There were no significant differences in hemodynamic measurements between new users and nonusers incident use analysis.
No differences were detected in mean right atrial pressure, cardiac index, or mixed venous oxygen saturation between SSRI users and nonusers in either analytic approach Table 2. See Table 1 legend for expansion of other abbreviation.
In the incident use analysis, new users were more likely than nonusers to be receiving an endothelin receptor antagonist No differences Paxil and pulmonary hypertension in adults the use of prostanoids, phosphodiesterase type 5 inhibitors, diuretics, warfarin, digoxin, thyroid hormone, or supplemental oxygen were detected. In the prevalent use analysis, high-affinity SSRI users were significantly more likely than nonusers to be Paxil and pulmonary hypertension in adults with prostanoids, diuretics, oxygen, and thyroid hormone replacement.
See Table 1 legend for expansion of other abbreviations. A small group of patients was using multiple SSRIs: A total of 16 incident use and three prevalent use subjects reported multiple SSRI use. See Table 1 legend for expansion of abbreviation.
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Kaplan-Meier survival estimates revealed that new users had significantly worse survival and were less likely to be free from the composite end point compared with matched nonusers at 2 years after enrollment In an unadjusted Cox proportional hazard model, new users demonstrated a significantly increased risk of death hazard ratio [HR], 1. In the prevalent use analysis, irrespective of SSRI affinity, there were no differences in 2-year survival from the time of enrollment between nonusers and SSRI users Fig 3A ; however, the unadjusted Cox proportional hazard model showed that high-affinity SSRI users had Paxil and pulmonary hypertension in adults worse freedom from the composite end point compared with nonusers HR, 1.
New users had a worse survival compared with matched non-SSRI users Fewer new SSRI users remained free from the composite end point vs matched nonusers See Figure 1 legend for expansion of abbreviations. See Figure 1 legend for Paxil and pulmonary hypertension in adults of other abbreviations.
See Figure 1 legend for expansion of other abbreviation. In this large, contemporary cohort of patients with PAH, our incident use analysis showed that SSRI use was associated with a greater risk of death and clinical worsening during a 2-year follow-up period from enrollment.
In the prevalent use analysis, high-affinity SSRI users had a similar survival but accelerated clinical worsening compared with nonusers. Paxil and pulmonary hypertension in adults findings were maintained despite adjustment for potentially confounding variables.
Materials and Methods In addition, a larger proportion of SSRI users were receiving PAH-specific medications, including endothelin receptor antagonists and prostanoids, compared with nonusers. Alternatively, the functional capacity Paxil and pulmonary hypertension in adults these patients could have been affected by the presence of depression, consistent with the results of a previous study indicating a trend toward worse baseline 6MWD and a higher FC in patients with symptoms suggestive of major depression.
In the prevalent use analysis, PCWP was only slightly higher among high-affinity SSRI users Paxil and pulmonary hypertension in adults with nonusers, and this difference is not considered clinically relevant. Discrepancies between hemodynamics and other indicators of severity raise the possibility that other factors like depression, obesity, or SSRI use may supplant the predictive value of baseline pulmonary hemodynamics.
Our findings are inconsistent with several previous reports. Compared with these studies, the present analysis provides greater statistical power because of the larger patient population, as well as a contemporary therapeutic background upon which to examine the association between PAH and SSRI use.
Our findings are concordant with a retrospective, population-based study examining the relationship between SSRIs and PAH in the Canadian health-care system. Although it was not associated with mortality or a worse outcome in the incident use analysis, depression may have counteracted favorable effects associated with SSRIs.
Depression is a well-established risk factor for heart failure and the progression of established atherosclerotic disease 3031 related to behaviors that impact health, particularly physical inactivity. In addition, depression may contribute directly to the pathogenesis and progression of PAH. Alternatively, alleviation of depression could have a beneficial effect on outcomes in PAH that is independent of any impact on pathogenic mechanisms; however, we were not able to evaluate any effect of SSRIs on depression in the present study.
Several aspects of our study limit our ability to definitively explore the relationship between PAH, SSRI use, depression, and serotonin biology. First, a longitudinal observational cohort study precludes conclusions about causality; we are limited to demonstrating associations.
Also, SSRI-user groups had a greater number of comorbidities compared with nonusers, raising the concern that adjustments for Paxil and pulmonary hypertension in adults cryptic group confounders were inadequate. In particular, the possibility of underreporting of depression would impede our ability to adjust for this potentially deleterious confounder.
In addition, we were unable to incorporate into our model longitudinal changes in BMI; however, we acknowledge that weight gain could impact both functional status and outcomes in these patients. Although an association was observed between anorexigen Paxil and pulmonary hypertension in adults and PAH in other SSRI users in the prevalent analysis, an evaluation of this interaction was precluded by the infrequency of exposures and lack of detail regarding the exposure intensity.
Despite these limitations, the much larger size of the REVEAL Registry database, its established validity as a resource for defining contemporary PAH epidemiology, and our ability to identify a sizable control population strengthen the present observations compared with previous cohorts.
use late in pregnancy and... These data contradict prior cohort studies demonstrating an association between improved survival and Paxil and pulmonary hypertension in adults use. Further prospective, randomized, and observational studies with more detailed analyses of PAH-associated depression and obesity will be necessary to better delineate these relationships. Dr Hill is the guarantor of the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. Miller, MS, and Michelle P.
Drs Sadoughi and Roberts contributed equally to the preparation of the manuscript. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. National Center for Biotechnology InformationU. Published online Apr 4. RobertsMD, Ioana R. Author information Article notes Copyright and License information Disclaimer.
Received Aug 22; Accepted Feb 7. This article has been cited by other articles in PMC. Outcome Measures Two outcome variables were assessed: Open in a separate window. Table 1 —Demographic and Clinical Characteristics. The number of patients within each subcategory is listed respectively by the analysis. Comorbid Conditions The prevalence of comorbid conditions was similar with the exception of obstructive airway disease between new users and nonusers in the incident use analysis Table 1.
Table 2 —Functional and Hemodynamic Variables. PAH-Specific and Other Medications at Enrollment In the incident use analysis, new users were more likely than nonusers to be receiving an endothelin receptor antagonist Mortality and Composite End Point Kaplan-Meier survival estimates revealed that new users had significantly worse survival and were less likely to be free from the composite end point compared with matched nonusers at 2 years after Paxil and pulmonary hypertension in adults Discussion In this large, contemporary cohort of patients with PAH, our incident use analysis showed that SSRI use was associated with a greater risk Paxil and pulmonary hypertension in adults death and clinical worsening during a 2-year follow-up period from enrollment.
Supplementary Material Online Supplement Click here for additional data file. Footnotes Drs Sadoughi and Roberts contributed equally to the preparation of the manuscript.
Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Blood 5-hydroxytryptamine in rats with pulmonary hypertension produced by ingestion of Crotalaria spectabilis seeds. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med.
Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Increased plasma serotonin in primary pulmonary Paxil and pulmonary hypertension in adults. A new role for an old molecule: Proliferation and signaling in fibroblasts: Analysis of responses to serotonin in the pulmonary vascular bed of the cat. Functional interactions between 5-hydroxytryptamine receptors and the serotonin transporter in pulmonary arteries.
J Pharmacol Exp Ther.
Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease.
Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells.
Relationship with the mitogenic action of serotonin. The efficacy of PAXIL was established in three week trials in adult patients failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia. A: Paxil (paroxetine hydrochloride) is in a class of medicines called Selective evaluate the Paxil and pulmonary hypertension in adults of suicidality in children, adolescents, and adults treated with these condition called persistent pulmonary hypertension of the newborn ( PPHN).
BACKGROUND: Pulmonary arterial hypertension (PAH) is a retrospective cohort study of 84 consecutive adult PAH patients who Patient-time while receiving high-affinity SSRIs (K(d)paroxetine, sertraline.
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Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn.
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