Levetiracetam in the preventive treatmentof transformed migraine: A prospective, open-label, pilot study

Abstract

Background: Most preventive agents used for transformed migraine (TM) have not been studied specifically for the treatment of this syndrome. Openlabel trials have demonstrated the effectiveness of levetiracetam in the treatment of refractory headaches.Objective: The aim of this study was to assess the effectiveness and tolerability of levetiracetam in the preventive treatment of refractory TM. Methods:This prospective, open-label, pilot study was conducted at The New England Center for Headache, Stamford, Connecticut. We included patients aged ~18 years with refractory TM according to the criteria proposed by Silberstein et al. All participants had failed on at least 1 but not more than 3 preventive drugs. Other preventive drugs were allowed if they had been received at a stable dose for >30 days. The dosage of the levetiracetam tablets ranged from 1000 to 3000 mg/d in 2 divided doses. The treatment phase lasted 3 months. The primary end point was headache frequency (expressed as the number of headache days per month), and the secondary end point was the frequency of moderate or severe headache (d/mo). Other end points were headache score, Migraine Disability Assessment (MIDAS) Questionnaire score, and Headache Impact Test (HIT-6) score. Statistical analyses were performed in the intent-totreat (ITT) population (patients who received at least 1 dose of study medication) using data subjected to the last-observation-carried-forward algorithm. We also conducted per-protocol (PP) analyses in patients who completed the study. Results:The ITT population consisted of 36 patients (26 women, 10 men; A.M. Rapoport et aLvs baseline). At baseline, the mean number of moderate or severe headache days was 16.8 d/mo compared with 13.2, 11.9, and 9.7 d/mo at 1, 2, and 3 months, respectively (P = NS, <0.01, and <0.01, respectively). The mean MIDAS score was significantly reduced at 3 months compared with baseline (40.8 vs 62.8 d/mo; P = 0.01). The mean HIT-6 score was 59.4 at 3 months versus 63.4 at baseline (P < 0.01). In the PP population, the mean (SD) headache frequency was reduced from 26.1 (4.1) d/mo at baseline to 14.3 (4.8) d/mo at the end of the study (P < 0.001). The mean (SD) headache score was reduced from 51.3 (17.1) at baseline to 34.0 (22.0) at 3 months (P < 0.016). Conclusion:The results of this study in patients with TM support the role of levetiracetam in the preventive treatment of refractory TM. (Curr Ther Res Clin Exp. 2005;66:212-221)

Efficacy and safety of levetiracetam for migraine prophylaxis: A systematic review

“…18 Six of the 11 studies included patients who had previously tried and failed, or were unable to tolerate, at least one other medication used for migraine prophylaxis. 19,21,26 The response rates and reduction in headache frequency and severity appear to be similar in these studies, when compared to the five studies that only included prophy- Based on available data, levetiracetam seems to be best tolerated by adults between 18 and 60 years old. 19,21,26 The response rates and reduction in headache frequency and severity appear to be similar in these studies, when compared to the five studies that only included prophy- Based on available data, levetiracetam seems to be best tolerated by adults between 18 and 60 years old.…”

“…While 2 studies showed statistically significant improvement in headache frequency after 1 month of treatment, 21,26 the studies in which patients were treated for 2-6 months showed that response rates continued to improve and outcomes were more likely to significantly differ from the comparator when treated for at least 2 months. While 2 studies showed statistically significant improvement in headache frequency after 1 month of treatment, 21,26 the studies in which patients were treated for 2-6 months showed that response rates continued to improve and outcomes were more likely to significantly differ from the comparator when treated for at least 2 months.…”

“…While 2 studies showed statistically significant improvement in headache frequency after 1 month of treatment, 21,26 the studies in which patients were treated for 2-6 months showed that response rates continued to improve and outcomes were more likely to significantly differ from the comparator when treated for at least 2 months. 18,19,21,23,26,27 Of these, 3 studies included only patients who had trialled other medications for migraine prophylaxis. 18,19,21,23,26,27 Of these, 3 studies included only patients who had trialled other medications for migraine prophylaxis.…”

“…The studies conducted for 6 months indicated that levetiracetam remains effective for migraine prophylaxis for the en- TA B L E 2 Recommended dosing schedule of levetiracetam for migraine prophylaxis [21][22][23][24][25][26][27][28] mood disorders such as irritability, which often were transient or could be improved by decreasing the dose. The longest treatment duration in any of the included studies was 6 months on levetiracetam.…”

Antiepileptic drugs and migraine

“…Limited information from retrospective and open label trials suggests that levetiracetam may have utility in migraine prophylaxis (Drake et al, 2001;Krusz, 2001a;Cochran, 2004;Miller, 2004;Rapoport et al, 2005;Vaisleb et al, 2005;Brighina et al, 2006). Levetiracetam has been marketed for epilepsy therapy since 2000, but its molecular target in brain was only recently identifed (Lynch et al, 2004).…”