NEONATAL FLUOXETINE WITHDRAWAL SYNDROME – A MOVEMENT DISORDER SECONDARY TO MATERNAL USE DURING PREGNANCY

Objectives: To document and report a movement disorder in newborn children exposed to maternal use of fluoxetine during pregnancy for the treatment of maternal depression/obsessive compulsive disorder, and alert clinicians to the abnormal neurologic status noted throughout the first month of life associated with an agent reportedly safe in pregnancy.

Methods: Four full term infants born to mothers utilizing fluoxetine in dosages of 60 to 80mg per day for treatment of depression or obsessive compulsive disorder are reported. These infants demonstrated within two hours of birth features of tachypnea, tachycardia, jitteriness, poor suck, hyperactivity and temperature instability. Measurment of norfluoxetine levels were obtained and correlated between mother and infant. Evaluation for other etiologies was carried out including chemistries, metabolic studies, thyroid studies, toxicology screens, sepsis evaluation, neuroimaging, cardiology, and neonatology consultations. Infants were monitored weekly following discharge and at two and three months. Developmental evaluation at six months months was available for three of the four infants.

Results: Full term infants exposed to prenatal fluoxetine throughout pregnancy with maternal doses of 60–80mg per day demonstrated a withdrawl syndrome that correlated with elevated fluoxetine levels in the exposed infants. Those infant serum levels were in the range of: 1–265ng/ml. The withdrwal syndrome resolved in 4–5 weeks in affected infants. Breast feeding was initially discouraged throughout this period. The findings of tremors/jitteriness, and shivering, hypertonicity, tachycardia and tachypnea were present in 4/4 infants. Presentation of clinical findings occurred within 24–72 hours in 3 infants, and at one week in 1 infant. Fluoxetine metabolites may be measured in breast milk and may also contribute to the syndrome. Other laboratory studies, electroencephalography, and neuroimaging were all normal. With sequential follow up, development assesed by clinical observation and developmental testing of these infants revealed that development and behavior were normal. Neonatal abnormalities after in utero exposure to fluoxetine could be quantified with maternal exposure and were self limited. Conclusion: Selective serotonin reuptake inhibitors have been reported to be safe during pregnancy. They are used extensively for the treatment of depression, mood disorders, and obsessive compulsive disorders. We have demonstrated that a specific withdrawl syndrome may be diagnosed in infants exposed in utero to fluoxetine. Fluoxetine doses greater than 20mg per day in pregnant women may produce this syndrome. Serum norfluoxetine levels in infants correlate with level of exposure. Breast feeding should be discouraged. Additional reports have documented no fetal anomalies but neurobehavioral findings in infants exposed to in utero SSRIs. Published reports suggest that SSRI exposure in developing animals is associated with altered neurotransmitter concentrations in brain regions; this model has been demonstrated with fluoxetine. Abrupt SSRI cessation may lead to decreases in intrasynaptic serotonin and rebound increases in receptor sensitivity. Variable presentation clinically post birth may be related to a combination of acute toxicity versus drug withdrawl. Other SSRIs have been evaluated for safety in pregnancy and lactation. Infants in this study were normal neurologically at the 2 and 3 month follow up evaluations and subsequently at 6 months without any long term effects. Fluoxetine has a prolonged half-life as does norfluoxetine The recognition of this syndrome and its ultimately favorable outcome is important as the use of SSRIs is widespread throughout the world during pregnancy.