OBJECTIVE: To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate. MATERIALS AND METHODS: Use of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester. RESULTS: Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose-related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure. CONCLUSIONS: Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.
OBJECTIVE: To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate. MATERIALS AND METHODS: Use of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester. RESULTS: Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose-related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure. CONCLUSIONS: Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.
Authors: Helen Dolk; Hao Wang; Maria Loane; Joan Morris; Ester Garne; Marie-Claude Addor; Larraitz Arriola; Marian Bakker; Ingeborg Barisic; Berenice Doray; Miriam Gatt; Karin Kallen; Babak Khoshnood; Kari Klungsoyr; Anna-Maria Lahesmaa-Korpinen; Anna Latos-Bielenska; Jan P Mejnartowicz; Vera Nelen; Amanda Neville; Mary O'Mahony; Anna Pierini; Anke Rißmann; David Tucker; Diana Wellesley; Awi Wiesel; Lolkje T W de Jong-van den Berg Journal: Neurology Date: 2016-04-06 Impact factor: 9.910
Authors: G M Goodwin; P M Haddad; I N Ferrier; J K Aronson; Trh Barnes; A Cipriani; D R Coghill; S Fazel; J R Geddes; H Grunze; E A Holmes; O Howes; S Hudson; N Hunt; I Jones; I C Macmillan; H McAllister-Williams; D R Miklowitz; R Morriss; M Munafò; C Paton; B J Saharkian; Kea Saunders; Jma Sinclair; D Taylor; E Vieta; A H Young Journal: J Psychopharmacol Date: 2016-03-15 Impact factor: 4.153