Use of SSRIs During Pregnancy May Cause Neurologic Symptoms in Newborns

Laurie Barclay, MD

July 15, 2003

July 14, 2003 — Newborns of mothers receiving fluoxetine or citalopram exhibited symptoms of central serotonin overstimulation for about four days, according to the results of a prospective trial published in the July issue of the Archives of General Psychiatry. The investigators warn of potential neurologic adverse effects from selective serotonin reuptake inhibitors (SSRIs) used during late pregnancy.

"SSRIs have gained wide acceptance in the treatment of mental disorders in pregnant women, but there seems to be an increased risk for neonatal adaptation problems after exposure to SSRIs in late pregnancy," write Kari Laine, MD, PhD, from the University of Turku in Finland, and colleagues. They cite previous studies suggesting that exposure to SSRIs during the third trimester may cause irritability, constant crying, eating and sleeping difficulties, and even seizures in newborns.

Between January 1, 1997, and August 31, 2000, Dr. Laine's group enrolled 40 pregnant women, including 20 who were taking SSRIs during pregnancy and breast-feeding and 20 who were not taking any psychoactive medications. All infants had neurologic assessments during the first four days of life and at two weeks and two months of age after delivery, as well as brain ultrasound and magnetic resonance imaging (MRI) 38 to 42 weeks after conception and at two months of age.

During the first two months of life, blood pressure, heart rate, and body temperature were similar in both groups. During the first four days of life, the serotonergic symptom score reflecting tremor, restlessness, and rigidity was four times higher in the SSRI group than in the control group (P = .008). Serotonin-related symptoms declined significantly in the SSRI group from the first four days to two weeks, and there was no significant difference in serotonergic symptom score between the two groups at two weeks.

Cord blood concentration of 5-hydroxyindoleacetic acid (5-HIAA) was significantly lower in the SSRI group than in the control group (P = .02). Umbilical vein 5-HIAA concentration was inversely correlated with serotonergic symptom score in the SSRI group (r = -0.66; P = .007) but not in the control group.

Because the symptoms resolved quickly while SSRI concentrations were decreasing, the authors suggest that the symptoms are related to central nervous system serotonergic overstimulation rather than to SSRI withdrawal syndrome.

"We report increased risk for central nervous system serotonergic adverse effects during the first days of life in newborns of mothers taking the SSRIs citalopram or fluoxetine during the third trimester of pregnancy," they write. "The clinical relevance of the present results is awareness of the psychiatrists who prescribe SSRIs during pregnancy and the pediatricians who treat the serotonin-related neurologic symptoms of the newborns during the first days of life. Although these effects seem to subside quickly, they may expose the infants to more serious neonatal complications such as convulsions."

The Turku University Hospital Research Fund supported this study.

Arch Gen Psychiatry. 2003;60:720-726

Reviewed by Gary D. Vogin, MD