Pharmacological aspects of neonatal antidepressant withdrawal.
Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary.


BACKGROUND
Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to explain the importance of antidepressant therapy during pregnancy and postpartum, summarize the important neonatal effects of antidepressants, and describe the potential teratogenic effects of antidepressants.
Ter Horst
Peter G J
PG
Department of Clinical Pharmacy, Isala Clinics, Zwolle, The Netherlands.
Jansman
Frank G A
FG
van Lingen
Richard A
RA
Smit
Jan-Pieter
JP
de Jong-van den Berg
Lolkje T W
LT
Brouwers
Jacobus R B J
JR
D000928:Antidepressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009357:Neonatal Abstinence Syndrome; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome
D000928:Antidepressive Agents; D003577:Cytochrome P-450 Enzyme System