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: Introduction: Psychiatric disorders are among the leading causes of disability in Western societies. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant drugs during pregnancy and the postpartum period. Over the last decade, conflicting findings regarding the safety of SSRI drugs during pregnancy and lactation have questioned whether such treatments should be used during this period. Areas covered: We discuss the main criteria that should be considered in the risk/benefit assessment of SSRI treatment in pregnant and/or breastfeeding patients (i.e., risks associated with SSRI use and with untreated depression as well as therapeutic benefits of SSRI and some alternative treatment strategies). For each criterion, available evidence has been synthesized and stratified by methodological quality as well as discussed for clinical impact. Expert opinion: Currently, it is impossible for most of the evaluated outcomes to distinguish between the effects related to the mother's underlying disease and those inherent to SSRI treatment. In women suffering from major depression and responding to a pharmacological treatment, introduction or continuation of an SSRI should be encouraged in order to prevent maternal complications and to preserve maternal-infant bonding. The choice of the right drug depends above all on individual patient characteristics such as prior treatment response, diagnoses and comorbid conditions.Expert Opinion on Drug Safety 01/2015; 14(3):1-15. DOI:10.1517/14740338.2015.997708 · 2.74 Impact Factor
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ABSTRACT: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth, and reduced birth weight after first trimester exposure to TNF-α inhibitors. Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol, or golimumab were evaluated in a prospective observational cohort study and compared to outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. In total, 495 exposed and 1532 comparison pregnancies were contributed from 9 countries. The risk of major birth defects was increased in the exposed (5.0%) compared to the non-exposed group (1.5%; ORadj 2.2; 95% CI 1.0-4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69; 95% CI 1.1-2.5), but not the risk of spontaneous abortion (16.2%; HRadj 1.06; 95% CI 0.7-1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (p = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs. This article is protected by copyright. All rights reserved.British Journal of Clinical Pharmacology 03/2015; DOI:10.1111/bcp.12642 · 3.69 Impact Factor
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ABSTRACT: There is controversy about the use of antidepressant medication during pregnancy. Decisions about their use are affected by understanding the risks of these medications causing pregnancy loss, congenital malformations, neonatal adaptation syndrome, persistent pulmonary hypertension of the newborn, autism spectrum disorder, or long-term neurocognitive deficits. Although some research has raised concerns about antidepressants causing harm to the fetus and neonate, other studies have disputed these findings or noted that any risks found do not exceed the risk of congenital problems found in 1% to 3% of neonates in the general population. Untreated depression during pregnancy can also cause harm from poor diet, substance abuse, suicidal behavior, or prematurity. Decisions about the use of antidepressants during pregnancy must be based on a risk-benefit analysis based on the best evidence of the risks of treating or not treating maternal depression.Journal of Nervous & Mental Disease 03/2015; 203(3):159-63. DOI:10.1097/NMD.0000000000000256 · 1.81 Impact Factor