Last week in clinical rounds we discussed a case of a woman with bipolar disorder who was planning a pregnancy. She had a long history of illness, experiencing primarily depressive episodes since her early 20’s. The only mood stabilizer that seems to have worked for her has been oxcarbazepine (Trileptal) and she is currently taking 300 mg twice per day. Previous medication trials included lithium, lamotrigine, and carbamazepine. None of these mood stabilizers were particularly effective for her compared to oxcarbazepine. She has also tried several atypical antipsychotics including aripiprazole, quetiapine, and olanzapine, either as monotherapy or in combination with a mood stabilizer. She has had difficulty tolerating these medications due to various side effects.
She stated that she wanted to maintain treatment with oxcarbazepine throughout her pregnancy, because earlier this year, when she attempted to taper the medication, she experienced a depressive relapse after reducing her dosage of medication by half.
Reproductive Safety Data for Oxcarbazepine
While we have sufficient data to support the use of certain anticonvulsants, such as lamotrigine (Lamictal), during pregnancy, there is less data on some of the other newer anticonvulsants, such as gabapentin (Neurontin) and topiramate (Topamax). We have even less information on the reproductive safety of oxcarbazepine.
Looking at the data from a Cochrane Database Review published last year, there have been a total of four studies which have included data on children exposed to oxcarbazepine monotherapy. The prevalence of major malformations for children exposed to oxcarbazepine (N = 238) was 2.39%, which did not differ from the prevalence observed in the control groups.
While these preliminary findings are certainly reassuring, the number of exposed children included in this analysis is very small. In order to identify a twofold increase in risk for relatively common malformations, such as cardiovascular defects, we need to analyze about 600-800 exposures. So when it comes to oxcarbazepine, we still have a ways to go.
These are difficult clinical decisions to make, and there is no “right” or “perfect” answer in these sorts of situations. The ultimate decision requires a consideration of the risks of exposure to a particular medication, but must also take into consideration personal preferences. In our discussion, we reviewed the following possible options.
Would it be possible to stop the oxcarbazepine during the first trimester of pregnancy to reduce the risk of exposure during the vulnerable time of organ formation? We know from previous studies that women with bipolar disorder who attempt to discontinue treatment with a mood stabilizer during pregnancy experience high rates of relapse, often during the first trimester. In addition, this might not be the best option for this particular patient as she experienced recurrent symptoms with a reduction in her dosage.
Would it be possible to find an alternative that is safer, or at least better characterized, with regard to reproductive safety? Lamotrigine rises to the top of that list; it is frequently used during pregnancy, and the most recent studies indicate that lamotrigine exposure during pregnancy has not been associated with an increased risk of malformations. This particular patient did not respond to lamotrigine as well as oxcarbazepine. Nor did she respond particularly well to other mood stabilizers. Some might consider a retrial of some of these medications, including lamotrigine; however, this switch may increaser her risk of relapse.
Would it be reasonable to consider maintaining treatment with oxcarbazepine during the course of her pregnancy? There are often settings where the best option for a particular patient may be to consider maintaining treatment with a particular medication in the absence of adequate reproductive safety data.
Ruta Nonacs, MD PhD
Weston J, Bromley R, Jackson CF, Adab N, Clayton-Smith J, Greenhalgh J, Hounsome J, McKay AJ, Tudur Smith C, Marson AG. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2016 Nov 7;11:CD010224. Review.