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 fact that all mood stabilizers are secreted into the breast milk, although their concentrations appear to vary considerably (Chaudron and Jefferson, 2000).
At this point, lamotrigine (Lamictal) is one of the most commonly used mood stabilizers in reproductive-aged women with bipolar disorder and has become a first-line treatment for childbearing women with epilepsy. We last reported on the use of lamotrigine in breastfeeding women in 2010.
Several small case series have reported that lamotrigine is passed to infants through the breast milk in relatively high doses and that infant serum levels range from 23 to 50% of levels found in the mother’s serum.
To date, the largest study we have on lamotrigine and breastfeeding comes from Newport and colleagues and includes a total of 30 women taking lamotrigine and their nursing infants. The authors reported that milk/plasma ratios were highly variable, ranging from 5.7% to 147.1%. The mean milk/plasma ratio was 41.3%. This type of variability has been reported in studies of antidepressants and other medications in nursing infants, indicating that milk/plasma ratios may be of limited utility in estimating the extent of exposure in the nursing infant.
Using measurements of maternal and infant plasma concentrations, it was estimated that the relative infant dose (RID) of lamotrigine was 9.2% and that the theoretical infant dose (TID) was o.51 mg/kg per day. This RID of 9.2% is lower than the RID cutoff of 10% frequently used as an empiric cutoff for assuming safety during lactation. The authors caution that clinicians should be advised that this rule of thumb is arbitrary and has not been objectively verified. However, it is reassuring that this dose is considerably lower than the dose of lamotrigine used to treat seizures in infants.
In these reports, no adverse events were observed in the nursing infants. To my knowledge, there has been only one published report of a serious adverse event in a breastfed infant. In this case, a 16-day-old infant experienced apneic episodes, followed by a cyanotic episode requiring resuscitation. The mother had used increasing doses of lamotrigine during her pregnancy, and at the time of her infant’s apneic episodes, she was taking 850 mg/day. The neonatal lamotrigine serum concentration was in the high therapeutic range. After the termination of breastfeeding, the infant recovered fully. Given that the mother was taking a dose of lamotrigine that was two to three times higher than the dose typically used, this case most likely represents an unusual event.
Various studies have addressed the short-term safety of antiepileptic drugs (AEDs) in nursing infants; however few have systematically assessed the long-term effects of exposure to these drugs on cognitive development. In a prospective study from Meador and colleagues which included 78 breastfed children exposed to AEDs (including but not limited to lamotrigine), no adverse effects of AED exposure through breast milk were observed in children at 6 years of age. In fact, breastfed children exhibited higher IQ and enhanced verbal abilities.
While the majority of professional and nutritional organizations support breast milk as the ideal form of nutrition for the infant in the first year of life, women taking psychotropic medications, such as lamotrigine, must weigh the benefits of breastfeeding against the risks of exposure to medication. More research is required to better assess the safety of lamotrigine in nursing infants; however, these findings are reassuring and are consistent with previous reports. Lamotrigine levels were detected in all infants assessed; however, the risk of adverse events is very low.
Ruta Nonacs, MD, PhD
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