A woman with depression and anxiety is in week 5-6 of pregnancy. The patient now requires treatment

Fråga: A woman with depression and anxiety is in week 5-6 of pregnancy. The patient now requires treatment with antidepressants. What is the risk for teratogenicity from treatment with clomipramine (Anafranil), paroxetine (Seroxat), citalopram (Cipramil) and fluvoxamine (Fevarin)?

Sammanfattning: There is no documentation of fetal damage associated with maternal use of tricyclic antidepressants. However, these drugs may give rise to neonatal adaption disturbances at parturition. Documentation of teratogenicity with the newer antidepressants, such as paroxetine, citalopram and fluvoxamine, is lacking. An older and more well-documented antidepressant, eg a tricyclic antidepressant, might be the best choice in the present case, since paroxetine, citalopram and fluvoxamine are relatively new drugs and documentation concerning their safety is limited. When using a tricyclic antidepressant, the plasma concentration can also be measured at the Department of Clinical Pharmacology, Huddinge Hospital, which would facilitate dose adjustments.

Svar: The question of teratogenicity in connection with the above-mentioned drugs has earlier been dealt with at the Drug Research and Information Centre (1,2,3,4). In summary: clomipramine, paroxetine, citalopram and fluvoxamine belong to category C concerning drug use during pregnancy, as do other antidepressants, which means that there is a possible risk of negative effects on the fetus without being directly teratogenic.

In treatment wiht clomipramine, adaptation disturbances have been seen in neonates whose mothers were treated with clomipramine at doses higher than 75 mg/day before delivery. It is recommended that if it is possible to discontinue the therapy, the drug should be stopped at least 10 days before partus in normal cases, but the required drug-free period is dependent upon the individual´s variations in metabolism (1,2).

Concerning paroxetine, an increased risk for human fetal damage has not been reported and documentation concerning neonatal adaption disturbances is lacking. Since paroxetine is a new drug which has been registered in Sweden for only three years, information on its safety is rather limited (3).

Documentation of treatment with citalopram in pregnant women is limited (4). In animal studies, a decreased postsurvival rate has been seen but no increased frequency of malformations.

There is no evidence of impaired fertility, reproductive performance or teratogenic effects from animal studies of treatment with fluvoxamine, but in the absence of further studies it has (5) been recommended that fluvoxamine not be given to pregnant women (5).

In general, exposure during the first three or four weeks after last menstrual period can be expected to lead to an all-or-none effect, with an early miscarriage if the fetus has been harmed (4). If the pregnancy proceeds normally, the risk of malformations caused by the drug is therefore negligible. 1 Drugline nr 09510 (year 1992)

2 Drugline nr 09308 (year 1992)
3 Drugline nr 09765 (year 1993)
4 Drugline nr 09575 (year 1992)

5 Dollery, Therapeutic drugs. 1991; 1: