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


OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Bar-Oz
Benjamin
B
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neonatology, Hadassah and Hebrew University Medical Center, Jerusalem, Israel.
Einarson
Thomas
T
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland.
Einarson
Adrienne
A
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Boskovic
Radinka
R
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
O'Brien
Lisa
L
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Malm
Heli
H
Department of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Bérard
Anick
A
The Ivey Chair in Molecular Toxicology, Department of Medicine, University of Western Ontario, London, Ontario, Canada; School of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Koren
Gideon
G
Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: gkoren@sickkids.ca.
D000014:Abnormalities, Drug-Induced / Q000000981:diagnostic imaging / Q000453:epidemiology*; D000328:Adult; D000649:Amniocentesis; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications / Q000188:drug therapy; D003863:Depression / Q000150:complications / Q000188:drug therapy; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011264:Pregnancy Trimesters; D014463:Ultrasonography
D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine