Clinical Medicine Reviews in Therapeutics

Lamotrigine (LTG) is a newer antiepileptic medication that has multiple indications for epilepsy including add-on therapy for partial onset epilepsy in adults. The primary antiseizure mechanism of action is blockage of voltage-sensitive sodium channels which stabilizes neuronal membranes and inhibits excitatory presynaptic neurotransmitter release. It has linear pharmacokinetics with rapid absorption with a tmax < 3 hours and no first pass metabolism. Bioavailability is nearly 100% with approximately 55% protein binding. Glucuronidation is the mechanism of elimination with a half life of approximately 24 hours. Co administration with an enzyme inducer shortens the half life to approximately 15 hours while enzyme inhibitors such as valproic acid lengthen the half life to over 60 hours. Immediate release preparations can be given once a day alone or with enzyme inhibitors and the recently available extended release preparation can be given once a day even with enzyme inducers. Pregnancy and oral contraceptive pills significantly alter the metabolism of LTG. Efficacy has been demonstrated in multiple clinical trials with a satisfactory safety profile. The most commonly reported CNS related adverse events include dizziness, diplopia, ataxia, headache and somnolence. The most commonly reported non-CNS related adverse event is rash, which is typically benign and self limited with only rare occurrence of Stevens-Johnson syndrome. LTG is a particularly good choice of antiepileptic medication in persons with comorbid mood disorders as it also has an indication for treatment of bipolar disorder and in the elderly population due to its tolerability, lack of interaction with anticoagulants and antiplatelet agents and linear pharmacokinetics.