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Treatment in Psychiatry   |    
Lamotrigine Dosing for Pregnant Patients With Bipolar Disorder
Crystal T. Clark, M.D., M.Sc.; Autumn M. Klein, M.D., Ph.D.; James M. Perel, Ph.D.; Joseph Helsel, B.S.; Katherine L. Wisner, M.D., M.S.
Am J Psychiatry 2013;170:1240-1247. doi:10.1176/appi.ajp.2013.13010006
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Presented in part at the international biennial congress of the Marcé Society for Perinatal Mental Health, Paris, October 3–5, 2012; and at the 52nd annual meeting of the New Clinical Drug Evaluation Unit, Phoenix, May 29–June 1, 2012.

The authors report no financial relationships with commercial interests.

Dr. Klein died in April 2013.

Supported by NIMH grant R01 MH 075921 to Dr. Wisner.

From the Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago; the Departments of Neurology, Obstetrics and Gynecology, Psychiatry, and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh.

Address correspondence to Dr. Clark (crystal.clark@northwestern.edu).

Copyright © 2013 by the American Psychiatric Association

Received January 02, 2013; Revised March 13, 2013; Accepted March 25, 2013.


Objective  Little information is available on the need for dosage changes for lamotrigine in pregnant women with bipolar disorder. The authors present new data on serial serum levels of lamotrigine in pregnant patients on lamotrigine monotherapy. They also review the epilepsy literature on use of lamotrigine during pregnancy.

Method  Lamotrigine serum samples were obtained from eight mother-infant pairs at different time points during pregnancy and the postpartum period.

Results  All of the women were taking lamotrigine throughout pregnancy. Serum-level-to-dose ratios were lower during pregnancy than the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg. Three patients had an increase of 50 mg to their daily dose across pregnancy. The change in serum lamotrigine levels in the postpartum period ranged from a 30% decrease to a 640% increase compared with the first level obtained during pregnancy. Level-to-dose ratios obtained within 4 weeks after delivery reflected a mean level 402% greater than the baseline level during gestation. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels.

Conclusions  The pattern of lamotrigine changes during pregnancy in these women with bipolar disorder was consistent with that described in the epilepsy literature.

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FIGURE 1. Ratio of Lamotrigine Serum Level to Daily Dose During Pregnancy and the Postpartum Perioda

a Ratio was calculated using the following formula: lamotrigine level (µg/mL) × 100/prescribed daily lamotrigine dose (mg).

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TABLE 1.Demographic and Clinical Characteristics of Eight Mothers Taking Lamotrigine During Pregnancy and Their Infantsa
Table Footer Note

a MDI=Mental Development Index; PDI=Psychomotor Development Index; GED=General Educational Development certificate; n/a=not available (patient 3 did not provide consent for her infant’s participation).



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