Bipolar disorder.(Drugs, Pregnancy, And Lactation)

As the use of anticonvulsants to treat bipolar illness has grown over the past decade, so has the number of women successfully treated with these medications who have questions about whether they should discontinue these drugs before they attempt to conceive, or what to do if they are already pregnant.

The anticonvulsants that have been most widely used for bipolar illness are sodium valproate and carbamazepine, and more recently, gabapentin (Neurontin), lamotrigine (Lamictal), oxcarbazepine (Trileptal), and tiagabine (Gabitril). Until recently, there have been few reproductive safety data available on the newer anticonvulsants.

Many women and their physicians are caught in a particularly vexing bind because two of the mainstays of bipolar therapy, lithium and sodium valproate, are known teratogens, though the teratogenicity of these two compounds is particularly different. The risk associated with first-trimester exposure ranges from a relatively modest 0.05% risk of Ebstein's anomaly with lithium to an approximately 8% risk of cardiovascular malformations and neural tube defects with sodium valproate. The latter is based on recent findings from the Antiepileptic Drug Registry at Massachusetts General Hospital (Am. J. Obstet. Gynecol. 187[6 pt. 2]:s137, 2002).

But the data that are accumulating on lamotrigine, approved in June for maintenance treatment of bipolar disorder, provide some welcome news for reproductive-aged women with bipolar disorder. An interim report on cases collected by the lamotrigine pregnancy registry maintained by the manufacturer, GlaxoSmithKline, since September 1992 indicates that the drug does not appear to be teratogenic. The report does note, however, that the sample size is not large enough to make definitive conclusions.

As of March, the pregnancy registry had collected information on more than 500 first-trimester exposures in women treated with the drug for bipolar illness and for epilepsy which did not demonstrate an increase in major birth defects associated with first-trimester exposure, supporting earlier reports.

The risk of teratogenicity was significantly increased with first-trimester exposure to the combination of lamotrigine and sodium valproate (more commonly used for epilepsy), but not with lamotrigine monotherapy: Among the 302 pregnancies exposed to monotherapy in the first trimester, there were 9 (3%) major birth defects, compared with 7 (10.4%) major birth ...