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

Abstract

AIMSThe aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category. METHODA systematic review of studies published between 1966 and November 2015 was conducted using EMBASE and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. RESULTSTwenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed. CONCLUSIONSParoxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

Patterns of antidepressant use during pregnancy: a nationwide population‐based cohort study

“…In Canada, between 2006 and 2015, only 55% of antidepressant prescriptions were given for depression while 19% were for anxiety disorders . In any case, the prevalence of antidepressant use during pregnancy in France appeared much lower than the estimated prevalence of depression during pregnancy, ranging from 7% to 20% . This raises the question of the extent of the potential undertreatment during pregnancy, while optimal management should be promoted owing to the risk of untreated depression, both for mother and child .…”

Selective Serotonin Reuptake Inhibitors as First‐Line Antidepressant Therapy for Perinatal Depression

“…The use of paroxetine (Paxil) during pregnancy is now commonly avoided, given concerns about potential risk for fetal cardiac malformations. Women who become pregnant when they are taking paroxetine are typically advised to discontinue use and substitute another SSRI if ongoing antidepressant therapy is desired …”

Meta‐analysis requires independent observations and freedom from bias

“…The recent meta‐analysis by Berard et al . associating exposure to paroxetine during pregnancy and risk of cardiac malformations suffers from two major problems: 1) duplication of data in the meta‐analyses and 2) difficulty disentangling the effect of paroxetine from confounding by indication (i.e. effects owed to depression, anxiety and correlated risk factors).…”

“…, analyzed by Berard et al . in one meta‐analysis, are also likely to include some duplicative subjects [ page 237].…”