Canadian Journal of Cardiology

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

Published:October 01, 2014DOI:https://doi.org/10.1016/j.cjca.2014.09.031

      Abstract

      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.

      Résumé

      Introduction

      La sérotonine a été associée au développement de l'hypertension artérielle pulmonaire idiopathique (HTAP). Les médicaments modulant les voies de la sérotonine, y compris les antidépresseurs, ont été associés à l'émergence de l’HTAP, avec des conclusions contradictoires quant à l’orientation de leur effet. Nous avons cherché à déterminer si l'administration d’antidépresseurs est associée à la survenance de l'HTAP.

      Méthodes

      Une étude cas-témoins emboîtée a été réalisée à l'aide du « United Kingdom Clinical Practice Research Datalink » et du répertoire de l’ « Hospital Episodes Statistics » entre le 1 er janvier 1988 et le 30 septembre 2011. Les cas de survenue de l’HTAP ont été identifiés et confrontés suivant des critères d’âge, de sexe, de pratique générale et de la date d’inscription à la pratique. Le risque relatif (RR) et les intervalles de confiance à (IC) 95% ont été estimés pour la prise d’antidépresseurs sur le risque de survenue de l'HTAP, avec une période de latence de 18 mois avant le diagnostic.

      Résultats

      Cent quatre-vingt-quinze cas d’HTAP ont été identifiés (incidence 3,84/million par année). La prise d'un antidépresseur a été associée à un risque accru de 67 % d'HTAP (RR, 1,67; IC à 95 %, 1,17 - 2,37). Le taux d'HTAP est similaire selon les classes d'antidépresseurs, avec des inhibiteurs sélectifs de la recapture de la sérotonine (ISRS) (RR, 1,67; IC à 95 %, 1,09-2,57) ou des antidépresseurs non ISRS (RR, 1,66; IC 95 %, 1,07-2,59). Suivant les analyses exploratoires et de sensibilité, aucun changement du risque n’a été observé, que ce soit avec différents temps de latence, les affinités des transporteurs de la sérotonine, ou les durées d'exposition.

      Conclusions

      L'utilisation d'antidépresseurs a été associée à une augmentation significative du risque de l’HTAP. Cependant, l’uniformité de ce risque pour l’ensemble des antidépresseurs et l'absence d'une relation dose-réponse suggère une association non causale.
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