Background: Migraine is characterized by moderate to severe recurrent headache lasting for 4–72 h. Cortical hyperexcitability may play a crucial role in migraine onset. Therefore, antiepileptic drugs, such as levetiracetam, may be beneficial. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of levetiracetam in migraine prophylaxis. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on migraine prophylaxis and levetiracetam published before May 2020. The main outcomes were number of patients with >50% headache frequency reduction, frequency of headache, and headache severity. Results: We identified 4 RCTs involving 192 patients and 4 prospective studies involving 85 patients. The overall data on number of patients with >50% headache frequency reduction, headache frequency, and headache severity were subjected to meta-analysis, which revealed significant differences between the levetiracetam and the placebo groups (risk ratio [RR] of number of patients with >50% headache frequency reduction = 0.46, 95% confidence interval [CI] = 0.35 to 0.61; weighted mean difference [WMD] of headache frequency per month = −3.78, 95% CI = −5.52 to −2.03; standard mean difference [SMD] of headache severity = −2.42, 95% CI = −4.47 to −0.37). Conclusion: Our study indicated that levetiracetam can significantly reduce headache frequency and severity in adults and children. Thus, oral levetiracetam can be a therapeutic option for migraine prophylaxis, especially concerning with the adverse effects or teratogenicity of other preventive treatments.

Original languageEnglish
Pages (from-to)755-764
Number of pages10
JournalJournal of the Formosan Medical Association
Issue number1
Publication statusPublished - Jan 2021


  • Antiepileptic drugs
  • Headache disorders
  • Levetiracetam
  • Meta-analysis
  • Migraine prophylaxis

ASJC Scopus subject areas

  • General Medicine


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