Newer anticonvulsants: lamotrigine, topiramate and gabapentin.
BACKGROUND The second generation antiepileptic drugs (AEDs), which include lamotrigine, topiramate, and gabapentin, have been introduced during the past 20 years. Because the newer AEDs differ in their pharmacokinetics from the first generation AEDs, it is hoped that the second generation AEDs will be less teratogenic. METHODS The findings in pregnancy cohorts and case-control studies concerning lamotrigine, topiramate and gabapentin-exposed pregnancies have been analyzed. RESULTS The rate of all malformations in lamotrigine monotherapy-exposed pregnancies has been between 2.0 and 5.6%, in comparison to baseline rates of 1.1 to 3.6% in two unexposed comparison groups. Compared to reference populations, a higher risk (0.4%) of isolated oral clefts has been observed in one cohort of 1562 lamotrigine-exposed pregnancies, but the risk was lower (0.1%) in other studies. In topiramate-exposed pregnancies, the rate of all malformations has been 4.2 to 4.9%, with an increase in oral clefts with and without other anomalies. The limited information available now for gabapentin has shown no evidence of teratogenicity. Concerning other developmental effects of these drugs, young children exposed to lamotrigine in utero have shown no deficits in cognitive function. Prenatal exposure to topiramate has been associated with an elevated frequency of small size for gestational age newborns. CONCLUSIONS The information available suggests an increased risk of oral clefts in infants exposed to topiramate, and perhaps lamotrigine, early in pregnancy, and of growth retardation for topiramate-exposed infants. Larger sample sizes are needed to clarify the questions that have been raised.
Genetics Unit, MassGeneral Hospital for Children, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114, USA. holmes.lewis@mgh.harvard.edu
Lewis B
LB
Holmes
Sonia
S
Hernandez-Diaz
D000014:Abnormalities, Drug-Induced; D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002972:Cleft Palate / Q000139:chemically induced*; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077206:Gabapentin; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000077213:Lamotrigine; D007858:Learning / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D012042:Registries; D012306:Risk; D000077236:Topiramate; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects*
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077213:Lamotrigine