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Lamotrigine for Migraine with Aura
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: The strong correlation between reduction of aura symptoms and migraine attacks stresses the potential role of aura-like events and possibly cortical spreading depression as a trigger for trigeminal vascular activation, and subsequently the development of migraine headaches.
Source: Lampl C, et al. Lamotrigine Reduces Migraine Aura and Migraine Attacks in Patients with Migraine with Aura. J Neurol Neurosurg Psychiatry. 2005:76:1730-1732.
In this controlled, 3-year, prospective, open study, 59 patients suffering from migraine with aura, or migraine aura without headache, for at least 1 year, received lamotrigine beginning at 25 mg/day for 1 month, and if needed, increasing by 25 mg/day each month to a maximum of 300 mg/day. Entry criteria required at least 1 headache/month graded as moderate to severe on a 4-step scale, and exclusion criteria included prophylactic headache medication in the 3 months preceding enrollment, previous seizure history treated with lamotrigine, hepatic, renal, or cardiac disease, and pregnancy or possibility thereof. Drug efficacy was evaluated by the maintenance of headache diaries documenting frequency and duration of headache and/or aura. Primary outcome measure was percentage of patients with at least a 50% reduction of migraine aura frequency, and secondary outcome measures included reduction of migraine headache and migraine aura frequency per month and reduction of migraine aura duration. Paired t test and Pearson's correlation were used for statistical analysis.
Lamotrigine significantly reduced monthly migraine aura frequency and duration in 44 of 59 patients, and 77% of responders (34/44) further experienced significantly fewer migraine headaches per month (mean, 2.1 vs 1.1; P < 0.001). Mean dose was 166.94 mg/d, most responding to 75-150 mg/d, and mean time to reach primary end point was 4.8 months (SD, 2.3 months). Lamotrigine appears to be an effective prophylaxis for migraine with aura, and up to 6 months of treatment should be offered before considering it ineffective. Given the open nature of this trial, further study of this potentially beneficial medication is warranted.
First approved in 1994 as adjunctive therapy for adult onset focal epilepsy, lamotrigine acts primarily by blocking sodium, and to a lesser extent, calcium channels. As monotherapy for seizures, it is comparable to phenytoin and carbamazepine, with fewer side effects and lower withdrawal rates. Adverse events mandate its discontinuation in 10.2% of patients (n = 3501), most often due to rash (3.8%), which, however, may be prevented by lower initial dosage, slower titration schedule, and avoiding co-administration of valproate, which slows lamotrigine metabolism. Stevens-Johnson syndrome occurs less often with lamotrigine compared to phenytoin, carbamazepine, and phenobarbital and, as a further advantage, lamotrigine is only minimally sedating (JAMA. 2004;291;605-614).
Lamotrigine is metabolized by the liver but has no effect on hepatic enzymes and, hence, no effect on the metabolism of oral contraceptives or other antiepileptic medication. In epilepsy, it provides the advantage of a broad-spectrum agent with minimal sedation or drug interactions. Ataxia, dizziness, diplopia, somnolence, and headache are the most frequently reported side effects, with additional adverse events including vomiting and tremor. Its most significant drawback is its slow titration schedule, requiring 2-3 months to reach a therapeutic maintenance dose, something that must be respected when used for migraine therapy as well.