Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors.
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: In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use.Drug, Healthcare and Patient Safety 09/2014; 6:109-29. DOI:10.2147/DHPS.S43308
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ABSTRACT: Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10–20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children’s developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers’ anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring’s emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams’ pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim Test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7–21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.Neuroscience 11/2014; DOI:10.1016/j.neuroscience.2014.10.044 · 3.33 Impact Factor