Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors.

Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clinical Therapeutics (Impact Factor: 2.59). 06/2007; 29(5):918-26. DOI: 10.1016/j.clinthera.2007.05.003
Source: PubMed

ABSTRACT Antidepressants have been commonly used by women of childbearing age. Recent studies suggest that paroxetine, a selective serotonin reuptake inhibitor (SSRI), might specifically increase teratogenic risk.
The purpose of this study was to quantify first-trimester exposure to paroxetine and birth defects and examine potential sources of bias in the in utero or postnatal detection of more congenital malformations among women with depression. We also sought to examine whether paroxetine was used for the same indications as other SSRIs among pregnant women.
This meta-analysis was designed to quantify malformation rates associated with the use of paroxetine. A search of the literature from 1985 to 2006 (English language) found in MEDLINE, EMBASE, REPROTOX, Scopus, and Biological Abstracts was conducted using the following terms: pregnancy outcome, congenital or fetal AND anomalies, malformations, cardiac/heart defects, AND selective serotonin reuptake inhibitors, paroxetine, and Paxil. Administrative databases of medication and medical services use in the Province of Quebec, Canada, were used to calculate the rates of ultrasound and echocardiogram in pregnancy and infancy in women/infants exposed to SSRIs and to compare the indications for general SSRI use versus paroxetine use.
Based on the studies analyzed, first-trimester paroxetine exposure was associated with a significant increase in the risk for cardiac malformation (odds ratio [OR], 1.72; 95% CI, 1.22-2.42). Women using antidepressants in pregnancy had a 30% higher rate of utilization of ultrasound in pregnancy. Infants of women who received SSRIs underwent approximately twice as many echocardiograms in the first year of life compared with children of women who used nothing. Significantly more women receiving paroxetine used the drug for anxiety or panic than women receiving other SSRIs (OR, 4.11; 95% CI, 2.39-7.08).
Based on the results of this metaanalysis, first-trimester exposure to paroxetine appears to be associated with a significant increase in the risk for cardiac malformation. However, a detection bias cannot be ruled out as contributing to the apparent increased detection of cardiovascular malformation of children exposed in utero to paroxetine. A significantly greater number of women were using paroxetine for anxiety or panic when compared with women using other SSRIs.

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    ABSTRACT: Part of three systematic reviews on the effects of psychotropic medication exposure in pregnancy, this paper critically reviews the literature on adverse effects of antidepressant use during pregnancy, and derives recommendations for clinical practice. Electronic databases were searched for original research studies examining the effects of gestational exposure to antidepressants on pregnancy, neonatal and longer-term developmental outcomes. Most results were derived from cohort (prospective and retrospective) and casecontrol studies. There were no randomized controlled trials. Congenital malformations: 35 studies identified, 12 demonstrated a significant association between antidepressant use in early pregnancy and congenital malformations. Pregnancy outcomes: 35 articles identified, outcomes measured rates of spontaneous abortion (4 out of 7 studies reporting elevated risk), preterm birth (15 out of 19 reporting elevated risk) and abnormal birth weight (8 out of 23 reporting elevated risk). Neonatal outcomes: 17 controlled studies including one meta-analysis were identified concerning neonatal adaptation. 15 studies showed an association between gestational exposure to antidepressants and neonatal adaptation difficulties. Three studies examined an association between selective serotonin reuptake inhibitor (SSRI) exposure and persistent pulmonary hypertension in the neonate with conflicting results. Longer-term developmental outcomes: 6 of 7 studies comparing developmental outcomes of children exposed to antidepressants in utero with non- exposed children reported no significant differences. Most of these medications remain relatively safe in pregnancy, but some significant areas of concern exist, particularly some evidence of higher risk of preterm birth, neonatal adaptation difficulties and congenital cardiac malformations (with paroxetine). The impact of these findings on the risk-benefit analysis when treating pregnant women with antidepressants is discussed.
    Australian and New Zealand Journal of Psychiatry 11/2010; 44(11):978-96. DOI:10.3109/00048674.2010.507543 · 3.77 Impact Factor