On 27 February 2011, several Danish media addressed the side effects from the antidepressant fluoxetine including death in newborns whose mothers were treated with fluoxetine.
There is a risk of side effects in the foetus and newborn when pregnant women receive treatment with fluoxetine. The risk of serious side effects from use of antidepressants is, however, small and should be weighed against the beneficial effect in pregnant women who suffer from a serious disorder requiring treatment. Doctors must carefully weigh the benefits against the risks from antidepressant therapy in pregnant women and prescribe the lowest possible dose for the shortest period of time.
Two reports of neonatal death following use of fluoxetine
Two cases of death have been reported where the mother's use of fluoxetine during pregnancy is suspected to have had a contributory role.
In the first case, the newborn died ten hours after birth. According to the autopsy report, death was due to heart-lung failure with pulmonary oedema and haemorrhage. There were no malformations, but suspicion of high pressure in the pulmonary circulation (persistent pulmonary hypertension). The risk of this complication is described in the Danish Medicines Agency’s newsletter Danish Pharmacovigilance Update from April 2010.
In the second case, the newborn died 11 days after birth. It appears from the medical history that there was suspicion of the newborn having withdrawal symptoms due to the mother’s use of fluoxetine. According to the autopsy report, the suspected cause of death was cerebral or circulatory disturbances due to exposure to fluoxetine in a newborn which already has an immature brain with relatively mild sequelae following anoxia from premature birth.
The Danish Medicines Agency’s comments
Pregnant women’s use of fluoxetine may be associated with a risk of side effects in the foetus and the newborn child when treatment is given in the beginning of pregnancy, but also when it is given at the end of pregnancy. If the mother has taken fluoxetine in the beginning of pregnancy, there is a risk of cardiac malformation. The risk of this complication was described in Danish Pharmacovigilance Update from April 2010. If the mother takes fluoxetine at the end of pregnancy, there is a risk of persistent pulmonary hypertension or withdrawal symptoms in the newborn. All three conditions may be life-threatening for the newborn.
However, there are also risks associated with not treating pregnant women who suffer from a disorder requiring treatment. For example, a severe depression that is not adequately treated may be associated with an increased suicidal risk. A depression could mean that the pregnant woman or recent mother is incapable of properly taking care of herself or her newborn child. Consequently, fluoxetine is not contraindicated during pregnancy.
Therefore, when doctors prescribe antidepressants to pregnant women, they should:
- carefully weigh the benefits against the risks of treatment
- use the lowest possible dose for the shortest period of time.
Reports related to other medicines of the SSRI type
Fluoxetine belongs to the class of selective serotonin reuptake inhibitors (SSRIs). In the period 1 January 1990 to 22 February 2011, the Danish Medicines Agency’s database of side effects received 20 reports describing side effects in newborns occurring as a result of the mother’s use of an antidepressant of the SSRI type during pregnancy.
The reports were distributed on citalopram (ten reports), sertraline (six reports), fluoxetine (two reports) and paroxetine (two reports). In addition to cardiac malformation, persistent pulmonary hypertension and withdrawal symptoms, the reported side effects were premature birth and low birth weight, etc.
In addition to the two reported cases of neonatal death after fluoxetine treatment, we have received reports of one case of intra-uterine death (in week 8) in connection with sertraline treatment, one case of acrania (absence of the cranium), verified in week 16, and subsequent induced abortion in connection with citalopram treatment, and one case of intra-uterine death (in week 33) in connection with paroxetine treatment.
The Institute for Rational Pharmacotherapy under the Danish Medicines Agency has recently reviewed the newest knowledge about side effects of antidepressants and pregnancy. Read the review (in Danish only) via the link in the factbox to the right.
The Danish Medicines Agency publishes a monthly newsletter called Danish Pharmacovigilance Update. You can subscribe to this newsletter via the link in the right-hand factbox.