Chest
Original ResearchPulmonary Vascular DiseaseSelective Serotonin Reuptake Inhibitors and Pulmonary Arterial Hypertension: A Case-Control Study
Section snippets
Setting, Design, and Ethical Approval
We conducted a population-based, nested case-control study between January 1, 1998 and March 31, 2010, using health-care databases in Ontario, Canada. This study was approved by the research ethics board of the Sunnybrook Health Sciences Centre.
Data Sources
We examined data from the publicly funded drug programs in Ontario, Canada, which provide coverage to all Ontario residents aged 65 years or older, recipients of social assistance and disability support, as well as those whose drug costs are high
Results
We identified 460 eligible case patients and 4,539 eligible control subjects (Fig 1). Most case patients were women (n = 334, 72.6%), and the mean age at index date was 65.3 years (SD, 16.4 years). Case and control subjects were well matched with respect to age, sex, neighborhood socioeconomic status, and the type of public drug program (Table 2). As expected, case patients were more likely to have seen a psychiatrist or a rheumatologist in the year prior to the index date.
In contrast to our
Discussion
In a large population-based case-control study, we did not find evidence that treatment with SSRIs protects against the development of pulmonary arterial hypertension requiring pharmacologic treatment. Our finding of a positive association between SSRI use and the development of pulmonary arterial hypertension was unexpected. Although this raises the possibility that the use of SSRIs is a risk factor for pulmonary arterial hypertension, we suspect the finding is more likely to reflect
Acknowledgments
Author contributions: Dr Dhalla is the guarantor of the article.
Dr Dhalla: contributed to the design of the study, the analysis and interpretation of the data, writing the first draft of the manuscript, and the final draft of the manuscript.
Dr Juurlink: contributed to the design of the study, the analysis and interpretation of the data, and the final draft of the manuscript.
Ms Gomes: contributed to the design of the study, the analysis and interpretation of the data, and the final draft of the
References (21)
- et al.
Primary pulmonary hypertension in HIV infection
Chest
(1991) - et al.
Prevalence of pulmonary hypertension in limited and diffuse scleroderma
Chest
(1996) - et al.
Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension
Chest
(2009) - et al.
Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension
Pulm Pharmacol Ther
(2006) - et al.
Depressive symptoms in pulmonary arterial hypertension: prevalence and association with functional status
Psychosomatics
(2010) - et al.
Health-related quality of life in patients with pulmonary arterial hypertension
Chest
(2004) - et al.
Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry
Chest
(2010) - et al.
Clinical classification of pulmonary hypertension
J Am Coll Cardiol
(2004) - et al.
Appetite-suppressant drugs and the risk of primary pulmonary hypertension
N Engl J Med
(1996) - et al.
Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine
Mol Pharmacol
(2000)
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Pulmonary Arterial Hypertension Secondary to Drugs and Toxins
2021, Clinics in Chest MedicineCitation Excerpt :A case-control study of patients enrolled in the SOPHIA registry found a protective effect of SSRIs in PH, with a decreased rate of PAH development and lower mortality once PH developed.116 Interestingly, a population-based nested case-control study found a positive correlation between SSRI use and PAH.117 In 2013, Sadoughi and colleagues118 published the results of an analysis exploring SSRI use and PAH outcomes using the REVEAL registry.
The Use of Antidepressants and the Risk of Idiopathic Pulmonary Arterial Hypertension
2014, Canadian Journal of CardiologyCitation Excerpt :It should also be emphasized that our cohort was an idiopathic PAH population, in which all secondary or associated causes of pulmonary hypertension had been excluded. The previous studies included either all patients with pulmonary hypertension of any cause (including cardiac and pulmonary disease) or all patients with PAH without exclusion of associated diseases.5,6 Our risk estimates should therefore be considered the most accurate to date.
Use of selective serotonin reuptake inhibitors and outcomes in pulmonary arterial hypertension
2013, ChestCitation Excerpt :In that study, 460 patients with PAH (defined as patients who received one or more prescriptions for a PAH-specific medication) were matched with 4,536 control subjects, and SSRI use was associated with an increased risk of PAH requiring pharmacologic treatment (adjusted OR, 1.55). The authors concluded that SSRIs are not protective against PAH and speculated that the association between SSRIs and PAH was likely the result of residual confounders, such as depression and anxiety.21 Studies of the REVEAL Registry have shown that depression is common in patients with PAH, significantly exceeding the prevalence in the general population (25% vs 6.7%, respectively).22
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Funding/Support: This study was funded by a grant from the Ontario Ministry of Health and Long-Term Care to the Ontario Drug Policy Research Network, which is led by Muhammad Mamdani and David Juurlink. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC).
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).