In addition to spina bifida and facial abnormalities, valproic acid and carbamazepine are associated with vitamin K-dependent clotting factor deficiency, possibly increasing the risk of bleeding in the fetus and neonate. It is not known whether folate supplementation beyond routine prenatal supplementation decreases these risks. Carbamazepine appears to increase the risk of cardiac malformations, oral clefts and urinary tract defects. Valproic acid may cause developmental delay. Because the newer anti-epileptic drugs lamotrigine (Lamictal), gabapentin (Neurontin) and topiramate (Topamax) are second-line agents for the treatment of BD and because there are very limited data for in utero exposure to these agents, these medications cannot be recommended for use in pregnancy (Morrell, 1996).

In a small (n=37) naturalistic report by Wisner et al. (2002), verapamil (Calan, Isoptin) effectively treated acute manic episodes and maintained mood stability in pregnant and nonpregnant women with BD. The authors noted that verapamil does not appear to be teratogenic but that further study is needed.

Until recently, high-potency neuroleptics were considered the safest antipsychotic medications in pregnancy (Altshuler et al., 1996). However, a study by Goldstein et al. (2000) found no evidence of increased risk in 23 cases of olanzapine (Zyprexa) exposure. This raises the question of whether olanzapine should be included as a possible treatment for pregnant women requiring an antipsychotic and/or a mood stabilizer. More data are needed.

The data on benzodiazepine use in pregnancy are mixed. Overall, the data suggest a very small (12 in 10,000) but increased risk of oral clefts associated with first trimester use (Altshuler et al., 1996; Dolovich et al., 1998). Late third-trimester use of benzodiazepines can be associated with perinatal syndromes such as hypotonia, withdrawal, poor feeding, apnea and low Apgar scores (Altshuler et al., 1996; McElhatton, 1994). Infrequent use, however, doesnot appear problematic.

When carried out with a multidisciplinary treatment team comprising a psychiatrist, anesthesiologist and obstetrician, ECT is safe in pregnancy and can rapidly treat severe psychiatric illness, including psychotic depression and uncontrollable mania (Miller, 1994). Special precautions must be taken during the procedure.

Conclusion

When treating women during pregnancy, a careful review of the most recent research is essential. A number of pharmaceutical manufacturers maintain registries of pregnancy outcomes in women using psychotropic medications. Referring to the Expert Consensus Guideline Series: Treatment of Depression in Women (Altshuler et al., 2001) and obtaining a consultation from a perinatal psychiatrist who specializes in treating women of childbearing age can be extremely helpful.

Dr. Zisook is a fellow in women's health at the Neuropsychiatric Institute and Hospital at the University of California, Los Angeles.

Dr. Burt is professor of clinical psychiatry and director of the Women's Life Center at UCLA's Neuropsychiatric Institute and Hospital.
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