The Use of Antidepressants and the Risk of Idiopathic Pulmonary Arterial Hypertension

Benjamin D. Fox, Laurent Azoulay, Sophie Dell'Aniello, David Langleben, Francesco Lapi, Jacques Benisty, Samy Suissa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Serotonin has been implicated in the development of idiopathic pulmonary arterial hypertension (IPAH). Drugs modulating serotonin pathways, including antidepressants, have been associated with the incidence of IPAH, with conflicting reports as to the direction of the effect. We aimed to determine whether antidepressant exposure is associated with the incidence of IPAH. Methods: A nested case-control study was conducted using the United Kingdom Clinical Practice Research Datalink and the Hospital Episodes Statistics repository between January 1, 1988 and September 30, 2011. Incident cases of IPAH were identified and matched to all controls in the case's risk set on age, sex, general practice, and date of registration with the practice. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated for the use of antidepressants on the risk of IPAH, with an 18-month lag period before the diagnosis. Results: One hundred ninety-five IPAH cases were identified (incidence 3.84/million per year). Use of any antidepressant was associated with a 67% increased risk of IPAH (RR, 1.67; 95% CI, 1.17-2.37). The rate of IPAH was similar across antidepressant classes, whether with selective serotonin reuptake inhibitors (SSRIs) (RR, 1.67; 95% CI, 1.09-2.57) or non-SSRI antidepressants (RR, 1.66; 95% CI, 1.07-2.59). In sensitivity and exploratory analyses, no change in risk was observed with different lag times, serotonin transporter affinities, or durations of exposure. Conclusions: The use of antidepressants was associated with a significantly increased risk of IPAH. However, the consistency of this risk across all antidepressants and absence of a dose-response relationship suggests a noncausal association.

Original languageEnglish
Pages (from-to)1633-1639
Number of pages7
JournalCanadian Journal of Cardiology
Issue number12
StatePublished - 1 Dec 2014


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