麻豆传媒

The use of paroxetine (Paxil) during the first trimester of pregnancy was associated with major cardiac and congenital malformations in the fetus compared to women who were unexposed to the drug, according to a small meta-analysis.

There were 23 studies included in the meta-analysis, and the 19 that examined major cardiac malformations found an overall increased risk of 28% (pooled odds ratio 1.28, 95% CI 1.11-1.47), reported , of the University of Montreal in Quebec, Canada, and colleagues.

The 16 studies that examined congenital malformations found a statistically significant 23% increased risk of major congenital malformations versus the non-exposure group (pooled OR 1.23, 95% CI 1.10-1.38), they wrote in the , although the absolute risks appear to still be very low.

Bérard told 麻豆传媒 that her team chose to examine paroxetine because not only have other studies shown that maternal use of the drug during pregnancy has been linked with heart defects, but because it is one of the most used antidepressants overall, there is a high prevalence of exposure. She added that she chose a meta-analysis because of the questions that still persist about whether observational study design or patient population (such as not accounting for maternal depression) contributed to the findings of prior studies.

"Maternal depression is a very important, debilitating condition associated with a lot of comorbidities, so from a public health point of view, it was very important to know what was going on with these women," said Bérard.

Risk of major cardiac malformations actually increased when looking at the 13 studies with adjusted estimates (pooled OR 1.35, 95% CI 1.23-1.62). These associations persisted even when evaluating women with paroxetine exposure compared to women prescribed a nonparoxetine antidepressant (pooled OR 1.66, 95% CI 1.05-2.12), but the authors note higher inter-study heterogeneity in this subgroup (I²=30.9%).

In eight studies, there was a 42% increased risk of bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07-1.89). Four studies apiece found that the risk more than doubled for atrial septal defects (pooled OR 2.38, 95% CI 1.14-4.97) and right ventricular outflow track obstruction defects (pooled OR 2.29, 95% CI 1.06-4.93) in the paroxetine group versus the group with no exposure.

Increased risk of pulmonary valve defects (unadjusted OR 1.84, 95% CI 0.75-4.54), left-sided defects (adjusted OR 2.1, 95% CI 0.5-8.7), and "other anomalies of the peripheral vascular system" (unadjusted OR 2.91, 95% CI 1.82-4.65) were each observed in one study.

When adjusted for publication bias, there was a slight attenuation in risk for congenital and cardiac malformations (pooled OR 1.16, 95% CI 1.01-1.33 and pooled OR 1.20, 95% CI 1.05-2.69, respectively).

But due to these risks, Bérard emphasized the importance of clinicians talking to patients with chronic conditions about the importance of planning their pregnancies, especially if they will have to continue to take medication throughout.

"Clinicians should advise patients with chronic conditions to plan their pregnancies to make things easier," she said. "At least they can understand and better manage the risks and the benefits [of their medication during pregnancy]."

The authors examined studies published between 1966 and 2015 from a variety of countries, including the U.S., Canada, U.K., Australia, and various European countries. Four studies used a case control design, while the remaining were cohort studies. The most common data sources were prescription databases linked to birth registries. The majority (nine studies) defined the exposure time window as 30 days prior to conception through the end of the first trimester.

Limitations include that the prevalence of specific defects are small, and more difficult to study, which explains why they are less likely to be reported in individual studies. Also, the report did not provide estimates of the absolute risks for malformations in paroxetine-exposed pregnancies. Estimates from put the absolute risk for right ventricular outflow track obstruction defects at 0.2% in pregnancies with paroxetine exposure.

Bérard pointed out that antidepressants are only one such treatment for depression -- that exercise and psychotherapy are other good options for this patient population, especially since the majority of pregnant patients only exhibit mild to moderate depressive symptoms. She said that more study is needed on the benefits of medication during pregnancy.

"We're always thinking there's a lot of benefit to using the medication, but so far in the literature, there are almost no studies that have looked at the benefits of using these medications," said Bérard. "The only way to re-frame the paradigm is to start studying the real benefits of these medications in pregnancy instead of imagining that it's really beneficial without having evidence-based data."

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