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The Pediatric Forum |

Neonatal Adverse Reactions After In Utero Exposure to Selective Serotonin Reuptake Inhibitors: Still Controversial

Louise Beaulac-Baillargeon, BPharm, PhD; Nina Boucher, BPharm, MSc
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Copyright 2006 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

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Arch Pediatr Adolesc Med. 2006;160(8):855-856. doi:10.1001/archpedi.160.8.855-b
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Levinson-Castiel et al1 reported neonatal abstinence syndrome (NAS) in 30% of selective serotonin reuptake inhibitor (SSRI)–exposed neonates in late pregnancy using the Finnegan NAS score. Although other reports exist of antidepressant-exposed neonates having a positive Finnegan score,2 the score was designed to assess opiates and not SSRI withdrawal. Moreover, the fact that newborns exposed to SSRIs in late pregnancy share some clinical features compatible with NAS does not indicate that the Finnegan score is representative of the same prevalence of symptoms or that all important symptoms are taken into account. We are currently analyzing data from a retrospective cohort of 66 SSRI- or serotonin-norepinephrine reuptake inhibitor–exposed newborns in late pregnancy; more than 20% showed decreased reactivity and/or decreased tonus during the first 72 hours of life, symptoms that are not assessed by the Finnegan score. Newborns also showed symptoms compatible with NAS in that time frame. Decreased reactivity or tonus have been reported in other cases and studies.3 This discrepancy shows that the etiology of these symptoms is still unclear.

An important point is that symptoms could be related either to serotonergic toxic effects,4 withdrawal syndrome, or adverse effects. Using the terms withdrawal or abstinence is assuming that the drug has disappeared, or nearly so, from the newborn's serum. The correlation between higher SSRI doses in the mother and higher Finnegan score does not demonstrate that symptoms are related to withdrawal. In fact, neonates' serum levels are essential to establish differential diagnosis between a toxic reaction and withdrawal5 and to decide treatment if necessary.

Time elapsed between birth and the emergence of symptoms should be interpreted with caution. It is unlikely that symptoms in the first days of life will be linked to withdrawal from fluoxetine because this drug and its active metabolite have a long half-life (4-6 days and 4-16 days, respectively) and, most likely, are still present in the newborn's serum. On the other hand, the fact that symptoms have not appeared during the first 24 hours of life does not demonstrate that it was a withdrawal reaction. Here again, drug levels may be helpful. However, drug action, which is slow to appear, may be slow to disappear, and relation to drug concentration might be hard to interpret.

Controversy remains on whether neonatal adverse reaction is due to a toxic reaction or to a form of withdrawal. Because both entities could be present,5 each case is unique and generalization is not yet possible.

AUTHOR INFORMATION

Correspondence: Dr Beaulac-Baillargeon, Faculty of Pharmacy, Laval University, Pavillon Vandry, 2230, Quebec G1K 7P4, Canada (louise.beaulac-baillargeon@pha.ulaval.ca).

Funding/Support: Dr Boucher received a doctorate scholarship from St-Francois d’Assise Hospital Research Center.

Levinson-Castiel  R, Merlob  P, Linder  N, Sirota  L, Klinger  G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants Arch Pediatr Adolesc Med 2006;160173- 176
PubMed
Rampono  J, Proud  S, Hackett  LP, Kristensen  JH, Ilett  KF. A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate Int J Neuropsychopharmacol 2004;7329- 334
PubMed
Nordeng  H, Spigset  O. Treatment with selective serotonin reuptake inhibitors in the third trimester of pregnancy: effects on the infant Drug Saf 2005;28565- 581
PubMed
Hegerl  U, Bottlender  R, Jurgen  G.  et al.  The serotonin syndrome scale: first results on validity Eur Arch Psychiatry Clin Neurosci 1998;24896- 103
PubMed
Koren  G. A new indication for therapeutic drug monitoring in the neonate Ther Drug Monit 2006;281
PubMed

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Levinson-Castiel  R, Merlob  P, Linder  N, Sirota  L, Klinger  G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants Arch Pediatr Adolesc Med 2006;160173- 176
PubMed
Rampono  J, Proud  S, Hackett  LP, Kristensen  JH, Ilett  KF. A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate Int J Neuropsychopharmacol 2004;7329- 334
PubMed
Nordeng  H, Spigset  O. Treatment with selective serotonin reuptake inhibitors in the third trimester of pregnancy: effects on the infant Drug Saf 2005;28565- 581
PubMed
Hegerl  U, Bottlender  R, Jurgen  G.  et al.  The serotonin syndrome scale: first results on validity Eur Arch Psychiatry Clin Neurosci 1998;24896- 103
PubMed
Koren  G. A new indication for therapeutic drug monitoring in the neonate Ther Drug Monit 2006;281
PubMed

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