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

Accumulating Evidence Suggests That Lamotrigine may Reduce the Frequency and Duration of Aura Manifestations in Various Conditions

In common forms of migraine with aura, a potential benefit of LTG was repeatedly observed in multiple small pilot and open studies (Table 2). D'Andrea et al reported first in 24 MA patients whose mean frequency of attacks was 6.1 ± 4.1 during a run-in period of 1 month, a decrease of MA attacks at 0.7 ± 1.3 per month with LTG administered over 3 months at 100 mg/day. No MA attack was reported in 13 among 21 patients who completed the study.[64] At the same time, in an open study of 13 individuals with typical MA attacks and 2 patients who reported only auras without headache, the median frequency of MA attacks at 1.3 per month observed during the 3 first months of treatment by LTG dropped to 0.1 during the posttreatment period of 4 months. Aura duration was reduced from a median value of 23–4 minutes.[65] More recently, in 57 MA patients among whom 3 had only auras without headache and 8 reported transient paresis during their auras, a reduction of the frequency of MA attacks larger than 50% was reported in 75% of individuals. Among the 44 responders, LTG significantly reduced not only the monthly mean frequency of attacks (1.5 ± 0.6 to 0.4 ± 0.7) but also the mean duration of aura manifestations (from 26.9 ± 10.8 min to 8.3 ± 13.6 min). The effect of treatment did not seem to differ according to aura types. One in 4 patients did not have any aura symptoms for more than 6 months. The mean dose of LTG was 167 mg (range 50–300) and no adverse event was reported.[66] In patients with more severe or complex aura symptoms, analysis of retrospective data also suggests a potential benefit of LTG. Thus, a structured questionnaire sent to patients having disabling aura manifestations and for whom a decision of treatment by LTG was made by a panel of neurologists (mean dose of 100 mg/day (range 50–300)) showed that the monthly frequency of MA attacks decreased from 4.2 to 0.7 attacks per month after 6 months of treatment in 30 participants.[67] The sample included particularly patients who suffered from repeated auras without headache (n = 6), migraine with aphasia during their aura (n = 8), migraine with prolonged aura (>60 minutes, n = 7), basilar-type migraine (n = 6), or hemiplegic migraine (n = 2). In line, Cologno et al reported in 3 patients having repeated basilar-type migraine who were treated by LTG at 100 mg/day, a total disappearance of MA attacks over 5 years.[68] The benefit of LTG was also reported in 3 cases of hemiplegic migraine belonging to a family diagnosed with FHM of type 2[69] and 2 patients with FHM of type 1.[70,71] LTG was also used in 9 patients with prolonged aura symptoms that usually did not respond to any preventative treatment, 2 individuals reported a partial remission and 3 others a complete relief of their attacks.[72,73] Finally, although metoprolol[74] and flunarizine[75] were usually deemed as the most effective treatment of vestibular migraine, the frequency of attacks was found more than halved in 18 of 19 patients with vestibular migraine who were treated by LTG and a complete relief was even detected in one fourth of them.[76] In a different study, a significant improvement was observed in 58 of 65 patients with vestibular migraine who were treated by LTG (reduction of headache, decrease of episodes of vertigo and of the dizziness handicap inventory score and increased reluctance to discontinue LTG).[77] In patients with rare conditions associated with aura-like symptoms, LTG was used only in few cases. In the rare visual snow syndrome for whom multiple preventative treatments of migraine (nonsteroidal anti-inflammatory drugs, amitriptyline, beta-blockers, benzodiazepines, serotonin reuptake inhibitors) appear ineffective, LTG tested in 5 patients was found either partially (n = 4) or totally effective (n = 1).[72,78–80] In one case of Sturge-Weber syndrome who had refractory headache associated with aura-like manifestations, a remarkable improvement was reported under LTG at 25 mg/day.[81] In another individual, escalation of LTG dose up to 200 mg/day prevented the occurrence of repeated and long-lasting hemiplegic aura-like manifestations.[82] These manifestations with a long progression of aura symptoms appear clearly distinct from ictal headache commonly misdiagnosed as MA.[83] The diagnosis of MA remains, however, challenging in the Sturge-Weber syndrome that can also lead to frequent epileptic seizures. In contrast, LTG was not evaluated in CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), the most frequent hereditary small vessel diseases that can lead to frequent attacks of MA.[84]