Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review.
BACKGROUND
There is ongoing debate about the safety of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic/noradrenergic antidepressants when used during pregnancy.


OBJECTIVE
This article reviews the available literature on the main safety concerns associated with the use of SSRIs and other serotonergic/noradrenergic antidepressants (serotonin-norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants) during pregnancy.


METHODS
English-language reports of analytical and descriptive studies, including case reports, case series, and meta-analyses, were identified through searches of MEDLINE, EMBASE, and PsycINFO (1966-April 2009). The search terms were fluoxetine, paroxetine, sertraline, Citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, reboxetine, duloxetine, SSRI, SNRI, NaSSA, and NRI in association with depression, pregnancy, prenatal exposure, miscarriage, spontaneous abortion, malformation, in utero exposure, and neonatal complications.


RESULTS
Paroxetine has been associated with significant risks of major malformation, particularly cardiac defects, when used during pregnancy. Significant associations between maternal exposure to SSRIs and both persistent pulmonary hypertension of the newborn and a self-limiting neonatal behavioral syndrome have been reported in a number of recent original studies and meta-analyses. Some studies have suggested a relationship between the use of SSRIs or other serotonergic/noradrenergic antidepressants and the occurrence of miscarriage, although these studies had methodologic limitations that affected the strength of the data. Evidence for a possible association between in utero exposure to SSRIs or other serotonergic/noradrenergic antidepressants and alterations in neurobehavioral development, bleeding, and QTc-interval prolongation is currently weak.


CONCLUSIONS
The available evidence suggests that SSRIs and other serotonergic/noradrenergic antidepressants should be used with caution during pregnancy, with careful follow-up of infants exposed to these agents in utero.
Tuccori
Marco
M
Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy.
Testi
Arianna
A
Antonioli
Luca
L
Fornai
Matteo
M
Montagnani
Sabrina
S
Ghisu
Narcisa
N
Colucci
Rocchina
R
Corona
Tiberio
T
Blandizzi
Corrado
C
Del Tacca
Mario
M
D000014:Abnormalities, Drug-Induced; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013723:Teratogens
D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; D013723:Teratogens