How does lamotrigine compare with other antiepileptic drugs in terms of congenital malformations in children?

CIAPPONI, AGUSTÍN

Cochrane Clinical Answers

Cochrane Clinical Answers

Año: 2019

Reviewers assessed the incidence of congenital malformations in children associated with lamotrigine versus carbamazepine, gabapentin, levetiracetam, oxycarbazepine, phenobarbital, phenytoin, topiramate, zonisamide, and valproate; no trial compared lamotrigine with primidone. Major malformations were rare, occurring most commonly with valproate (8% of infants; all values on average), phenytoin (7%), and phenobarbital (6%); rates for lamotrigine ranged from 1.8% to 3.5% across comparisons. In absolute numbers, the greatest reductions with lamotrigine were observed when compared with valproate (23 vs 83 per 1000 infants), phenytoin (35 vs 66 per 1000 infants), and phenobarbital (18 vs 55 per 1000 infants). Reviewers assessed neural tube, cardiac, orofacial cleft/craniofacial, and skeletal/limb malformations separately; similarly, highest rates were observed with valproate, phenytoin, and phenobarbital, although rates were ≤ 4% in all groups across all comparisons. It is worth noting that none of the studies were RCTs and all were classified as being at high risk for selection bias and high or unclear risk for blinding of outcome assessment. In addition, details of the regimens used for each antiepileptic drug were not reported, making it difficult to assess the generalizability of results to clinical practice.