Paroxetine and neonatal withdrawal syndrome

Abstract

We report a case of neonatal withdrawal syndrome after in utero exposure to paroxetine 20 mg/day. The infant’s symptoms, such as poor neonatal adaptation, respiratory distress, decerebrate posturing, irritability and tremors, commenced soon after birth and persisted for 5 days. All neonates exposed to antidepressants, particularly serotonin reuptake inhibitors (SSRIs), during the last trimester should be followed-up closely for adverse symptoms.

Background

Depressive symptoms and major depressive disorders are not uncommon in pregnant women, ranging between 7% and 20%.¹ SSRIs are among the most commonly used medications, with a prescription frequency of 2.3% in pregnant women. Although most babies born to women who take SSRIs during pregnancy have no adverse outcomes,² there is accumulating evidence that maternal SSRIs treatment during pregnancy may cause adverse pregnancy outcomes, such as a higher rate of spontaneous abortions,³ lower birth weight and shorter gestation,⁴ or an increased proportion of children with minor anomalies.⁵ Maternal SSRIs treatment during the third trimester has been linked to various neonatal complications, including symptoms of neonatal withdrawal⁶ and persistent pulmonary hypertension of the newborn.⁷ We report a case of neonatal withdrawal syndrome after in utero exposure to paroxetine.

Case presentation

A boy was born at 38 weeks’ gestation (birth weight 3.060 kg) to a 32-year-old mother who had used paroxetine 20 mg/day during the last 6 months of pregnancy. At birth, the infant showed poor neonatal adaptation, respiratory distress (Apgar score at 1’=4) that required intensive treatment for a short period of time (Apgar score at 5’=8). Soon after birth, the infant became tachypnoeic, he put on decerebrate posturing, showed increased tonus and reflexes, irritability and tremors.

Investigations

The blood tests gave no evidence of infection or derangement of electrolytes; the blood glucose value was normal. An electroencephalogram (EEG) performed at 3 h of life was normal as was the cerebral ultrasound and the diffusion weighted MRI.

Treatment

At 6 h of life the infant developed seizure-like movements and lorazepam bolus was administered intravenously. The symptoms were interpreted as withdrawal syndrome but the chlorpromazine treatment was not started because neonatal abstinence score was repeatedly under 8.

Outcome and follow-up

Only supportive care was needed and symptoms disappeared by 5 days of age.

Discussion

The increasing use of SSRIs during pregnancy warrants careful examination of their effects on the fetus and newborn infant. Fetal exposure to SSRIs has not been associated with an increased incidence of major congenital malformations, but there is growing evidence that it is associated with a neonatal abstinence syndrome (NAS).⁸ Some symptoms of withdrawal, such as jitteriness, tachypnoea, hypertonicity, temperature instability and diarrhoea, can be attributed to serotoninergic hyperstimulation⁹ and maximum severity of symptoms would be expected to occur shortly after birth, because drug exposure does not continue. Even if it is difficult to assess the specific SSRIs that are more likely to cause NAS symptoms, infants exposed to paroxetine show the more severe neonatal withdrawal syndrome. This case report confirms the severity of this syndrome and its correlation with paroxetine treatment in the last two trimesters of pregnancy. Infants exposed to the drug only during the first and second trimesters did not exhibit neonatal complications as did those exposed in the third trimester. This strongly suggests that paroxetine exposure near term may compromise fetal and neonatal health and that brief adverse events further support drug exposure as the causing mechanism.¹⁰ The decision whether to use antidepressants in pregnancy should be taken after careful consideration of the benefits and risks for both mother and child. In some cases, the benefits of treatment may well outweigh the risks. Untreated depression in pregnancy appears to carry substantial perinatal risks, such as preterm birth, restricted fetal growth, pre-eclampsia, spontaneous abortions and delayed cognitive and emotional development. These adverse effects may be caused by psychopathological events that have physiological effects on the fetus. Depression may also lead to unhealthy behaviour that can indirectly affect the outcome of the pregnancy.¹¹ A recent cohort study has also found out that women who discontinue antidepressant medication, close to conception, experience more frequent relapses of major depression during pregnancy than those who maintain their medication.¹²

Infants exposed to SSRIs should be closely monitored after birth for a minimum of 48 h and, particularly those who develop severe symptoms, should be followed to assess the long term effects of prolonged exposure to SSRIs.

The high prevalence of NAS in infants exposed to SSRIs in utero should be brought to the attention of family doctors, psychiatrists, gynaecologists, paediatricians, and the possibility of such symptoms needs to be discussed with women.

Learning points

• The high prevalence of NAS in infants exposed to SSRIs in utero should be brought to the attention of family doctors, psychiatrists, gynaecologists, paediatricians, and the possibility of such symptoms needs to be discussed with women.

• Infants exposed to SSRIs should be closely monitored after birth for a minimum of 48 h and, particularly those who develop severe symptoms, should be followed to assess the long-term effects of prolonged exposure to SSRIs.

• Further research is needed to better define the effects of SSRIs on newborns.