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

Among Potential Migraine-preventative Drugs, Lamotrigine Interferes With Voltage-gated Ionic Channels and Reduces Experimental CSD

Lamotrigine (LTG) (Lamictal®, GSK) (6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine) is a phenyltriazine derivative that differs chemically from other types of antiepileptic drugs. LTG was initially approved for treatment of generalized and partial seizures.[52] At clinically relevant doses, LTG strongly reduces brain hyperexcitability and CSD in various experimental models.[45,47,53–55] The drug inhibits several voltage-gated sodium channels in the CNS[22] through a voltage- and frequency-dependent blockade. Administration of LTG results in limiting intense firing while single-action potentials and basal activity remains unaffected.[33] LTG also blocks TRESK potassium channels with moderate affinity.[56] Interestingly, LTG has high affinity and can inhibit similarly N-(Cav2.2), P/Q-(Cav2.1), and R-type (Cav2.3) voltage-gated calcium channels.[32,57] These presynaptic channels are key players for spreading depolarization and glutamate release during CSD.[58] Other potential effects include the blockade of HCN channels,[59] 5-HT1,[60] and 5-HT3 receptors[61] or the reduced synthesis of nitric oxide[62] which all may represent potential therapeutic targets in migraineurs.[63]