What is known about the use of sertraline during pregnancy?

Fråga: What is known about the use of sertraline during pregnancy?

Sammanfattning: Sertraline and the other SSRIs do not appear to increase the risk of teratogenic effects, but the available data on sertraline in this area is limited (with 855 exposures found). There have, however, been case reports of neonatal withdrawal syndrome. Dose reduction prior to delivery has been suggested but this can cause an increased risk of relapse. No data on long-term effects after in utero exposure to sertraline has been found.

Svar: This question has previously been dealt with in Drugline (1-5) and an update and summary of the information in this area has been done. In general, published studies of treatment with sertraline during pregnancy are limited. Available data concerning the use of sertraline and the other selective serotonin reuptake inhibitors (SSRIs) during pregnancy do not suggest an increased risk of teratogenicity. As a precaution, antidepressive therapy should always be administered at the lowest effective dose during pregnancy.

Data from the Swedish Medical Birth Register concerning the use of sertraline in pregnant women does not imply an increased risk of malformations compared to the general population (6). Among, 568 women exposed to sertraline during pregnancy, 11 (1.94%) delivered a child with a malformation. With a probability of 99% the malformation rate is between 0.44 and 3.43%. The overall malformation rate in the population is 3.53%. In 1999, a study from the Swedish Medical Birth Registry was published (7). The study contained 546 women using SSRIs during pregnancy out of which 34 used paroxetine. The frequency of stillborn infants, minor and major malformations did not differ from the general population.

In a prospective cohort study, the pregnancy outcome in 267 women treated with sertraline, paroxetine or fluvoxamine was evaluated (2-3,8-9). Out of these, 147 women used sertraline. No significant differences in the incidence of major malformations, miscarriages, stillbirths, birth weight or gestational age between the cases and controls were found. The outcomes of women who took an SSRI throughout the pregnancy were no different to those treated only during the first trimester. One of the major limitations of this study is that the three antidepressants were analysed as a group, instead of analysing each substance separately (10).

Prematurity and neonatal adaptation difficulties have been observed with increased frequency in infants exposed to sertraline in the third trimester (11). The study confirming this has, however, been criticized for its unrandomized groups and the fact that they did not correct for the severity of the disease in women requiring pharmacotherapy (10). Prematurity is seen not only for the SSRIs but also for other antidepressants and is possibly due to patient related conditions or other factors rather than the antidepressants themselves (7). For example, women using antidepressants smoke more during their pregnancy than other women.

Regarding the possibility of neonatal withdrawal syndrome, few case reports have been published. There is one case of a boy who at the age of day one had symptoms of agitation, restlessness, poor feeding, constant crying, insomnia and an enhanced startle reaction (1,2,5). The symptoms were intense for 48 hours and then began to subside over the next few days. A second case report describes an infant born with nystagmus to a mother treated with sertraline two weeks prior to delivery (12). Nystagmus is an occasional side effect of sertraline treatment in adults. The nystagmus disappeared spontaneously after 72 hours.

The WHO adverse drug reaction-monitoring centre in Uppsala has received reports of a total of eight cases of neonatal withdrawal syndrome (13). It should be noted that the WHO database does not include a homogeneous evaluation of reported cases due to differences among reporting countries. Infants exposed to SSRIs during the last trimester might need close follow-up for withdrawal syndromes after birth. Dose reduction or discontinuation of drug therapy a few weeks before labour has been suggested (10,14). This may, however, cause a relapse of the disease, which can be of greater clinical importance.

SSRIs are known to cause bleeding disorders in adults. Two case reports involving infants with increased hemorrhagic tendency after exposure to fluoxetine and paroxetine in utero have been reported (15). It is important to be aware of this increased risk of hemorrhage in the newborn after SSRI treatment.

The decision to prescribe an antidepressant during pregnancy must always be made after consideration of the risks and benefits in each individual case (16,17). Discontinuation of antidepressant therapy may be associated with an increased risk of relapse and with an increased risk of suicide. Besides risk to the mother, there is an increased risk to the infant with prematurity and low birth weight. The development of the infant may also be affected, with delayed motor development, reduced growth and lower IQ than infants of mothers treated for their depression. Long-term effects in infants whose mothers were treated with sertraline during their pregnancy have not been studied and any conclusions in that area can therefore not be done. One study, observing children between the ages of 16 and 86 months who had been exposed to fluoxetine in utero has been done (18). The authors concluded that fluoxetine did not seem to affect neurobehavioural development.