Topiramate (marketed as a Topamax), in addition to its use for the treatment of epilepsy, is now being prescribed to reproductive aged women for a broad spectrum of indications, including migraine headaches, weight control, and mood stabilization. Limited information is available on its reproductive safety; however, the preliminary data we do have raises some concerns regarding the use of topiramate in pregnancy.
Because breastfeeding has many psychological and medical benefits for both the mother and her child, many women would like to breastfeed. However, all medications taken by the mother are secreted into the breast milk. While various studies have addressed the safety of antiepileptic drugs (AEDs) in nursing infants, none have systematically assessed the long-term effects of exposure to these drugs on the cognitive development of children exposed to these agents through breastfeeding. This is an especially important issue as it has been demonstrated that certain AEDs, most notably valproic acid, may negatively affect the developing brain, a process which occurs in utero and into the first few decades of the child’s life.
Previous studies have indicated that infants exposed to valproic acid in pregnancy are at increased risk for a range of malformations, including neural tube defects. While these studies have shown an association between valproic acid and various malformations, they have been limited in their ability to quantify the risk of certain, less common malformations. To do this, large population-based case–control studies are more appropriate.
Anticonvulsants are not only used for the treatment of epilepsy but are now used with increasing frequency for the treatment of mood disorders, such as bipolar disorder. Recent studies have indicated that anticonvulsants may negatively affect bone mineral density, as well as increase fracture risk. This seems to be especially common with the older anticonvulsants (e.g., phenobarbital, carbamazepine, phenytoin, and valproate); however, the data regarding lamotrigine and other newer anticonvulsants is much more limited. While bone loss is more often seen with long-term use of these medications, several reports indicate that decreased bone density may also be detected within the first 1-5 years of use.
After last week’s post, we received several comments regarding the use of mood stabilizers in breastfeeding women, specifically asking which is safer: lithium or lamotrigine.
Women with bipolar disorder are vulnerable to postpartum illness, and it is generally recommended that mothers continue treatment with a mood stabilizer throughout the postpartum period to reduce their risk of relapse; however, this recommendation is complicated by the all mood stabilizers are secreted into the breast milk, although their concentrations appear to vary considerably (Chaudron and Jefferson, 2000).
There are strong parallels between the clinical management of bipolar disorder and epilepsy, and women with these disorders face significant challenges while pregnant or planning to conceive. In this setting, treatment decisions must balance the risks of recurrence of severe illness with the risks of potential harm to the fetus when certain medicines are taken during pregnancy.
A clinician asks: “I am a psychiatrist treating a patient with Bipolar Disorder on Seroquel and Topamax. I would like to know what information is available regarding the safety of these medications to the infant if used during breastfeeding.”
While anticonvulsants, such as lamotrigine (Lamictal), topiramate (Topamax), and gabapentin (Neurontin), are being used with increasing regularity for the treatment of women with bipolar disorder, we have limited information with respect to the reproductive safety of the newer anticonvulsant agents. In 2006, we reported on preliminary data indicating an increased risk of oral clefts among infants exposed to lamotrigine during the first trimester of pregnancy.
Women with bipolar disorder are at increased risk for recurrence of illness during pregnancy. Therefore, many women with bipolar disorder elect to continue treatment with medications during pregnancy after weighing the risks and benefits of various treatment options with their physicians. Lamotrigine (Lamictal) is an anticonvulsant used to treat bipolar disorder. While the safety data on this relatively new anticonvulsant in pregnancy is limited, pregnancy registry data suggests that lamotrigine may pose less of a risk to the developing fetus than with older anticonvulsants, such as valproate (Depakote). With lamotrigine emerging as an effective and relatively safe treatment for pregnant women with bipolar disorder, more attention is now being paid to the effects of pregnancy on lamotrigine levels.
