Teratogenicity lamotrigine

Of the newer anticonvulsants, lamotrigine, gabapentin, tiagabine, and vigabatrin have little or no teratogenic potential in animals, whereas oxcarbazepine and topira-mate are teratogenic in rodents. However, animal studies are not necessarily apphcable to humans and chnical data are stiU insufficient to assess the effects of newer drugs on the development of the human fetus (153). 

Vajda FJ, Graham JE, Hitchcock AA, O Brien TJ, Lander CM, Eadie MJ. Is lamotrigine a significant human teratogen Observations from the Australian Pregnancy Register. Seizure 2010 19(9) 558-61. 

The risk of foetal malformation is increased in women with epilepsy compared with the general population. Minor dysmorphic features are most frequent, but more severe forms such as facial clefts and neural tube defects are not uncommon. The two major forms of neural tube defects are (i) anence-phaly, a lethal malformation, and (ii) spina bifida—a closure defect in the spinal eolumn that may lead to paralysis of the lower limbs. The rates of malformations are about 3% with CBZ and lamotrigine (LTG), 7% with VPA, and 15% with combinations of two or more AEDs. It is probable that AEDs have several different teratogenic mechanisms. Low folate levels appear to be associated with increased risks of foetal malformations in women on AEDs. Furthermore, it has been suggested that maternal C677T MTHFR polymorphism or some abnormality related to methionine synthetase increase the risk of foetal malformation in patients on AEDs (Mills et al. 1995). 

All new information on the teratogenic effects of the most frequently used antiepileptic drugs has been reviewed [61 ]. T e prevalence of major congenital malformations associated with exposure to carbamazepine or lamotrigine was only marginally increased from expected, while malformation rates with valproate have been reported to be 2-4 times higher. This adverse outcome appears to be dose-related. 

Teratogenicity A female infant was born with micrognathia, low-set ears, facial dys-morphism, and unilateral radius aplasia to a mother who had used lamotrigine 1(X) mg/day and oxcarbazepine 12(X) mg/day during pregnancy for seizures [170 ]. 

Berwaerts K, Sienaert P, De Fruyt J. Teratogenic effects of lamotrigine in women with bipolar disorder. Tijdschr Psychiatr 2009 51(10) 741-50. 

An analysis of birth defects associated with newer generation antiepileptic medications was performed [45 ]. Lamotrigine was associated with a slightly higher risk of isolated oral clefts (0.1-0.4%) compared to reference populations. The rate of all malformations associated with topiramate was 4.2-4.9%, with an increase in oral clefts with and without other anomalies. The limited information available now for gabapentin has shown no evidence of teratogenicity. 

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