Lamotrigine in the Prevention of Migraine With Aura

A Narrative Review

Dan Buch, MD; Hugues Chabriat, MD, PhD


Headache. 2019;59(8):1187-1197. 

In This Article

The Safety and Tolerance of Lamotrigine Appears Among the Highest of all Molecules Preventing Migraine Attacks

Furthermore, among 122 randomized controlled trial of LTG monotherapy totalizing 18,698 patients, Bloom and Amber found only 8.3% of benign and self-limited morbiliform rash but 0.04% of Stevens-Johnson syndrome and Lyell syndrome.[87] Fatal severe cutaneous adverse reactions related to LTG use are extremely rare and estimated at 0.01 per 1000 patient-year (3.5% of severe cutaneous adverse reactions) and imposes strict compliance with the drug scheduled regimen as well as the immediate cessation of drug intake at first signs suggestive of immunoallergic reactions (eg, high fever, influenza-like symptoms, conjunctival itching, cutaneous erythema, progressive blistering, mucosal erosions, or hematological abnormalities).[88] But common adverse effects of LTG, observed in more than 1/10 cases, include headache and benign cutaneous rash.[89,90] Of utmost importance, the risk of major congenital malformations among children who were exposed to LTG appears null in a prospective registry of 18 years.[91] In addition, among 96 studies including 58,461 individuals, the risk observed under LTG did not differ from that reported in healthy individuals in contrast with findings obtained with most other antiepileptic drugs.[92,93] Moreover, a large prospective cohort study shows that fetal exposure to LTG does not affect IQ or any detectable neuropsychological ability in children up to 6 years of age.[94] LTG concentration increases linearly with a first-order pharmacokinetics and its half-life elimination can vary between individuals from 24.5 to 43.4 hours (mean value of 31.2 hours). LTG can be also administered only once daily using its extend release formulation.[95] LTG is only subject to a reciprocal plasmatic level reduction of approximately 50% with using estroprogestative pills. Abrupt increases of LTG plasmatic level can be thus observed during the free-pills periods in women.[96–98] Progestin use does not lead to such a reciprocal plasmatic level change.[99] Interestingly, the lack of important GABAergic modulation of LTG may explain the lack of significant sedative effects and cognitive dysfunction in contrast with that observed with Topiramate or Valproate also used as migraine preventive treatments.[100] LTG can be finally used in its generic form which is also of potential interest in the large population of migraineurs.