What is known about the use of fluvoxamine during pregnancy?

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

Sammanfattning: There are limited data on treatment with fluvoxamine during pregnancy, a total of 113 exposures have been found. However, there is no need to end a pregnancy due to exposure to the drug. Treatment with other SSRIs that have been studied (such as citalopram and fluoxetine) have not been associated with an increased risk for teratogenicity and these might be a better choice.

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 fluvoxamine during pregnancy are very limited and exposure should preferably be avoided. However, the available data does not suggest any major teratogenic risk when using fluovoxamine during pregnancy and there is no need to terminate the pregnancy if the fetus has been exposed at an early stage.

No cases have been found in the Swedish Medical Birth Registry (6).

In a prospective cohort study, the pregnancy outcome in 267 women treated with sertraline, paroxetine or fluvoxamine was evaluated (7-9). Out of these, 26 women used fluvoxamine. No significant differences in the incidence of major malformations, miscarriages, stillbirths, birth weight or gestational age between the cases and the controls were found. The outcomes of women who took a selective serotonin reuptake inhibitor (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).

In a large report on pregnancy outcomes with women treated with antidepressants, 66 women had been treated with fluvoxamine (11). No relationship could be established between in utero exposure to antidepressants and adverse pregnancy outcome. In another report, fluvoxamine was taken during the first trimester in 21 pregnancies (7,12). The outcomes included one ectopic pregnancy, five spontaneous abortions, two elective abortions (where one was due to a 47XXX chromosomal abnormality), nine normal full term newborns, one premature delivery and three lost to follow-up.

In general, women treated with antidepressants have a tendency to deliver pre-term more often than other women (13,14). This is seen not only for the SSRIs but also for other antidepressants and is possibly due to the patients underlying conditions or other factors (ie women using antidepressants tend to smoke more during their pregnancy than other women) rather than the antidepressant.

Neonatal withdrawal syndrome has been observed for the other four SSRIs (14-17), but no case reports on such incidence have been observed for fluvoxamine. 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 (18). 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 the consideration of the risks and benefits in each individual case (14,19). 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. Theoretically the development of the infant may also be affected, with delayed motor development, reduced growth and lower IQ than in infants of mothers treated for their depression. However, long-term effects of infants whose mothers were treated with fluvoxamine during pregnancy have not been studied and any conclusions in that area can therefore not be drawn. One study, observing children between the ages of 16 and 86 months who had been exposed to fluoxetine in utero has been done (15). The authors concluded that fluoxetine did not seem to affect neurobehavioral development.