Amritha Bhat, MD, MPH
In the United States, about 1 in 10 fetuses are exposed to psychotropic medications. It is important to maintain optimal mental and physical health for the mother in the perinatal period, and at the same time ensure a safe environment for fetal growth, and perinatal mental health providers are often faced with the dilemma–to prescribe or not to prescribe?
There are several improvements in the availability of data and the FDA’s new Pregnancy and Lactation Labeling rule is more informative than previously defined pregnancy risk categories. But there is still minimal high-quality data to guide the prescribing of medications during pregnancy and lactation.
Here I review recent updates in information on prescribing mood stabilizers in pregnancy and postpartum.
In recent years, lamotrigine has become the preferred medication to treat bipolar disorder during pregnancy. Initial concerns for risk of cleft lip and palate in a baby exposed in utero to lamotrigine have not been supported by recent cohort studies and meta-analyses, and the current consensus is that there is no increased risk of malformation in the fetus if the mother is prescribed lamotrigine during pregnancy. There are reports that when used by breastfeeding mothers, lamotrigine can lead to high concentrations in infant serum. However a review of 122 women with bipolar disorder and epilepsy showed no increase in the number of infant adverse events reported. These data suggest that mothers may continue to take lamotrigine while breastfeeding, and the infant needs to be monitored for possible adverse effects such as rash. A very recent naturalistic cohort study of women with bipolar disorder also suggests that lamotrigine is as effective as lithium in preventing severe postpartum episodes.
For women who require lithium to treat their bipolar disorder, we have new information on lithium dosing strategies based on a retrospective cohort study of a 113 pregnancies. The authors recommend that, as lithium levels drop in the first and second trimesters, lithium should be monitored once every three weeks until 34 weeks gestation and then once a week until delivery. Lithium is excreted by the kidney, and renal functions normalize slowly in the postpartum period, so levels should be monitored twice weekly for the first two weeks postpartum. It is important to obtain preconception lithium levels so that the dose during pregnancy can be adjusted to maintain levels in the therapeutic range. Dosing lithium twice a day can minimize side effects. Previous recommendations to decrease or discontinue lithium at onset of labor are no longer emphasized as it is possible to continue lithium while closely monitoring levels. In the postpartum period it may be advisable to administer lithium targeting a higher therapeutic level (>0.8mmol/L) in order to reduce the risk of postpartum relapse.
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.
Valproate , of course, should never be prescribed during pregnancy. Although valproate is compatible with breastfeeding, the high teratogenicity and other risks such as polycystic ovarian disease imply that it should not be a medication of choice in reproductive age women.
There is some new information on less frequently used mood stabilizers such as gabapentin, which is associated with increased rates of preterm birth and low birth weight, and topiramate, which is associated with higher risks of oral clefts, hypospadias, and coarctation of aorta.
There is a new medication on the horizon for the treatment of postpartum depression. Not yet ready for clinical use but showing promise is the intravenous infusion of brexanolone, which is a derivative of a progesterone metabolite. Women with severe depression showed significant improvements within 24 hours of receiving this medication. Stay tuned for updates as the phase three clinical trials for this medication are completed!
Information in this field changes rapidly, and some useful resources for you to access for updated information include ReproTox and LactMed . To speak to a perinatal psychiatrist and obtain consultation on any mental health related question for perinatal patients, you can call the free telephone consultation service for providers, the Perinatal Psychiatry Consultation Line at 206-685-2924.