Is there any risk to the fetus when the mother is treated with buspirone and nefazodone during preg

Fråga: Is there any risk to the fetus when the mother is treated with buspirone and nefazodone during pregnancy? Is there any risk of neonatal withdrawal symptoms? A 42-year-old woman, pregnant in week 9, is treated with buspirone (Buspar) and nefazodone (Nefadar).

Sammanfattning: According to the limited data available, use of buspirone and nefazodone during pregnancy does not seem to increase the risk of congenital malformations. Long-term effects on the developing brain have not been studied. No reports of neonatal withdrawal symptoms have been found.

Svar: Questions concerning the use of buspirone and nefazodone during pregnancy have previously been dealt with in Drugline (1,2,3). There is very limited clinical data on the use of either of these substances during pregnancy.

Buspirone is an anti-anxiety agent with a high affinity for serotonergic receptors. No congenital malformations have been observed in small studies (4). Late appearing side-effects, such as neurobehavioural changes, have not been investigated.

Nefazodone is an antidepressant, which combines SSRI activity and antagonistic properties at the 5-HT2A receptor. One recently published article with 147 women taking either nefazodone (89) or trazodone (58) during their pregnancy has been found (5). No increased risk of major malformations compared to the normal population was found. The study did not investigate neurobehavioural changes in the children.

For both drugs it is recommended to use them with care during pregnancy, but exposure in early pregnancy is not an indication for abortion (6, 7). In the Swedish Medical Birth Registry there are 84 exposures for buspirone with three children having a malformation (3.6 %) (8). For nefazodone there was one child (out of a total of 41 exposures) with a malformation (2.4 %). This is comparable with the incidence in the normal population (3.5 %).

No reports of neonatal withdrawal symptoms have been found for any of the drugs. Reports have however been found for SSRIs and might therefore also be expected for nefazodone (9).

Drugs during pregnancy should always be administered in the lowest effective dose. Both buspirone and nefazodone is metabolised by cytochrome P-450 3A4 (CYP3A4). Nefazodone is also a potent inhibitor of the same enzyme (10). Higher concentrations of buspirone might therefore occur, which must be taken into consideration.