Paroxetine – Paxil – Linked To Increase in Cardiac Birth Defects

Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy and Director, Réseau Québécois de recherche sur le médicament (RQRM) and Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy University of Montreal and Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine

Dr. Anick Bérard

MedicalResearch.com Interview with:
Anick Bérard PhD FISPE
Research chair FRQ-S on Medications and Pregnancy
and Director, Réseau Québécois de recherche sur le médicament (RQRM)
and Professor, Research Chair on Medications, Pregnancy and Lactation
Faculty of Pharmacy University of Montreal
and Director, Research Unit on Medications and Pregnancy
Research Center
CHU Ste-Justine

Medical Research: What is the background for this study? What are the main findings?

Dr. Bérard: Paroxetine (one of the most used antidepressant during pregnancy) has been studied extensively over the past 10-12 years. In 2005, a black box warning was put on the Paxil label to caution against use during pregnancy due to the increased risk of cardiac defects. The ACOG 2010 guidelines also suggested switching to other antidepressants during pregnancy. Over the past decade, many studies, including meta-analyses, were performed on on paroxetine use during pregnancy and the risk of cardiac malformations – but results were sometimes statistically significant or not, although a consistent increased risk was observed. It was thought that these variations could be explained by different study designs, patient populations, and because maternal depression was not always taken into account correctly. Hence, we undertook another meta-analysis (the most recent and updated) to quantify the risk of cardiac defects overall as well as specific cardiac defects associated with paoxetine use during pregnancy and to assess the impact of study designs, maternal depression and patient population on the effect of the risk.

We found that women using paroxetine during the first trimester of pregnancy (critical time-window for malformations) were 23% more at risk of having a child with malformations (15 studies combined) – baseline risk of malformation is 3-5% and thus a 23% increased risk is 3.69-6.15% absolute risk; women using paroxetine during the first trimester of pregnancy were 28% more at risk of having a child with cardiac malformations (18 studies combined) – baseline risk of cardiac malformation is 1% and thus a 28% increased risk is 1.28% absolute risk. We found that paroxetine was increasing the risk of many specific cardiac defects as well. Although the estimates varied depending on the comparator group, study design, and malformation detection period, a trend towards increased risk was observed.

Medical Research: What should clinicians and patients take away from your report?

Dr. Bérard: Depression is an important and prevalent condition during pregnancy. It should not be left untreated. Antidepressants are one treatment option for mild to moderate depression – 80-85% of depressed pregnant women have mild to moderate depression.

1) plan your pregnancy – discuss treatment options such as exercise, psychotherapy, antidepressants (evaluating the risks and benefits for each treatment options),

2) wichever option choosen, acknolwedge the risk and benefit,

3)never stop antidepressants overnight – discussion with your treating physician is essential.

In our previous research, we have shown that over 20% of depressed pregnant women remain depressed throughout pregnancy even while using antidepressants. The benefit of using these drugs during pregnancy is not guaranteed. Indeed, given that pregnancy increases metabolism, an increase in dosage should be initiated once the pregnancy begins in order to have the same pre-pregnancy efficacy. In practice however, dosage remains the same of is decreased once the pregnancy is diagnosed because of fear of teratogenicity – risk/benefit ratio is not in favor of benefits in the majority of the cases unlike people might think.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Bérard: Given that the occurence of malformations is due to the inhibition of serotonin caused by paroxetine (an SSRI), the current research (under way) focuses on the class effect for all SSRI. Given their similar mechanism of action, paroxetine seems to be similar to other SSRI. Hence, there seems to be class effect (and not a drug specific effect).

Citation:

Br J Clin Pharmacol. 2015 Nov 27. doi: 10.1111/bcp.12849.

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: A systematic review and meta-analysis.

Bérard A1,2, Iessa N1,2, Chaabane S1,2, Muanda FT1,2, Boukhris T1,2, Zhao JP1,2.

Anick Bérard PhD FISPE (2016). Paroxetine – Paxil – Linked To Increase in Cardiac Birth Defects