GlaxoSmithkline (GSK) have recently issued a Dear Healthcare Professional letter to notify our healthcare professionals of the preliminary findings of a retrospective epidemiological study which showed a 2-fold increase in the risk of congenital malformations in infants born to mothers who took paroxetine during the first trimester compared to other antidepressants.
Paroxetine (Seroxat®) is indicated for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalised anxiety disorder and post-traumatic stress disorder. Seroxat CR® is approved for the treatment of major depressive disorder. The company has updated the package inserts of both Seroxat® and Seroxat CR® to reflect this risk under the Pregnancy subsection.
Background
The study, initiated by GSK was conducted in 3,581 pregnant women. Preliminary analysis showed that infants of mothers who were given paroxetine in the first trimester of pregnancy have a 2.2 fold increase [adjusted odd ratios of 2.2 (95% CI: 1.34-3.63)] for congenital malformations as a whole and a 2.08 fold increase [2.08 OR (95% CI: 1.03-4.23)] for cardiovascular malformations alone. Majority of the cardiovascular malformations reported were ventricular septal defects. The prevalence of congenital malformations as a whole and cardiovascular malformations alone were approximately 4% and 2%, respectively. This study did not include a comparison to infants who were not exposed to any antidepressant. Therefore, these data should be viewed in the context of the overall prevalence of congenital malformations within the general population, which is estimated in the US to be approximately 3% for any malformation and approximately 1% for cardiovascular malformations alone.1
Other independent studies conducted earlier on pregnancy outcome following first trimester exposure to serotonin reuptake inhibitors (SSRIs), including paroxetine, have not provided evidence for an increased risk of major malformations with these medications. Additional epidemiology studies would need to be conducted to more fully understand these preliminary findings.
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Recommendations
Physicians are advised to carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy and to discuss the risks and benefits as well as treatment alternatives with their patients. Paroxetine should be used during pregnancy only if the potential benefit outweighs the possible risk to the foetus.
The workgroup of the MOH Clinical Practice Guidelines on Depression would like to refer healthcare professionals to a statement on page 17 of the guidelines which states that “In pregnancy and nursing mothers, the relative risks and benefits of using antidepressants must be carefully weighed. There is no evidence of increased risk of teratogenesis or spontaneous abortions following exposure to antidepressants such as tricyclic antidepressants and SSRIs in early pregnancy.” The workgroup would like to advise all healthcare professionals that this statement might no longer be valid in the context of the current information available on paroxetine.
References
