Update on bipolar disorder. (Drugs, Pregnancy, and Lactation).

Bipolar disorder is a chronic relapsing illness with a deteriorating course over time, particularly if there have been multiple episodes. This creates a bind for women in their reproductive years because stopping the medication increases their relapse risk.

Complicating the matter is the trend away from treatment with lithium and divalproex sodium (Depakote), toward newer anticonvulsants and atypical antipsychotics. We know more about the reproductive safety of lithium and divalproex sodium, even though both are teratogenic. But data on newer antimanic drugs are sparse, putting the clinician between a teratologic rock and a clinical hard place.

Last month at the American Psychiatric Association's annual meeting, we reported on the first prospective study of bipolar women who had discontinued mood stabilizers at about the time they got pregnant. Within 3 months, half of the 50 women had relapsed, and by 6 months about 70% had relapsed. This supports the findings of our earlier study a chart review, which found a high relapse rate among women who had stopped taking lithium during pregnancy.

Lithium is clearly safer during pregnancy than divalproex sodium. Many of us learned in medical school that lithium is a known teratogen and should not be used in pregnancy but we now know that its teratogenicity is relatively modest: The risk of Ebstein's anomaly is about 0.05% among babies exposed to lithium in the first trimester.

Divalproex sodium, which is increasingly used as first-line therapy is about 100 times more teratogenic than lithium, with a 5% risk for neural tube defects among children exposed to this anticonvulsant during the first 12 weeks of gestation. This makes it a less-than-ideal choice for women during the childbearing years.

The anticonvulsants that are being used increasingly are topiramate (Topa-max), gabapentin (Neurontin), and lamotrigine (Lamictal). These drugs are sometimes used as monotherapy and often as adjunctive therapy raising concerns because there are almost no reproductive safety data on these agents.

There are no human studies of topiramate and gabapentin. The manufacturer of lamotrigine has a pregnancy registry, and preliminary data do not suggest that risk of malformations is increased when this drug is used as monotherapy but it is too early to reach conclusions.