Anticonvulsant drugs for migraine prophylaxis

Abstract

Background: This review has been split and updated in a series of four new reviews, all with the author byline Linde M, Mulleners WM, Chronicle EP, McCrory DC. The new titles are: 1. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. 2. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010611. DOI: 10.1002/14651858.CD010611. 3. Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010609. DOI: 10.1002/14651858.CD010609. 4. Antiepileptics other than gabapentin, pregabalin, topiramate, and valproate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010608. DOI: 10.1002/14651858.CD010608. Readers are referred to those reviews for updated results. Anticonvulsant drugs seem to be useful in clinical practice for the prophylaxis of migraine. This might be explained by a variety of actions of these drugs in the central nervous system. Objectives: To describe and assess the evidence from controlled trials on the efficacy and tolerability of anticonvulsants for preventing migraine attacks in adult patients with migraine. Search methods: We searched PubMed (1966-December 2005), EMBASE (1974-December 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2005), and handsearched Headache and Cephalalgia through April 2006. Selection criteria: Studies were required to be prospective, controlled trials of anticonvulsant drugs taken regularly to prevent the occurrence of migraine attacks and/or to reduce the intensity of those attacks. Data collection and analysis: Studies were selected and data extracted by two independent reviewers. For migraine frequency data, standardized mean differences (SMDs) were calculated for individual studies and pooled across studies. For dichotomous data on significant reduction in migraine frequency, odds ratios (ORs) and numbers-needed-to-treat (NNTs) were similarly calculated. Adverse events were analyzed by calculating numbers-needed-to-harm (NNHs) for studies using similar agents. Main results: Twenty-three papers met the inclusion criteria. In total, data from 2927 patients were considered. Analysis of data from 10 trials (n = 902) demonstrates that anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days as compared to placebo (WMD -1.31; 95% confidence interval [CI] -1.99 to -0.63). Data from 13 trials (n = 1773) show that anticonvulsants, considered as a class, also more than double the number of patients for whom migraine frequency is reduced by 50% or more relative to placebo (RR 2.25; 95% CI 1.79 to 2.84; NNT 3.9; 95% CI 3.4 to 4.7). For six trials of sodium valproate and divalproex sodium, NNHs for five clinically important adverse events ranged from 7.0 to 18.8. For six trials of topiramate, NNHs for seven adverse events (100 mg dose) ranged from 2.4 to 31.2. Authors' conclusions: Anticonvulsants appear to be both effective in reducing migraine frequency and reasonably well tolerated. There is noticeable variation among individual agents, but there are insufficient data to know whether this is due to chance or variation in true efficacy. Acetazolamide, clonazepam, lamotrigine and vigabatrin were not superior to placebo (one trial each). Relatively few robust trials are available for agents other than sodium valproate/divalproex sodium and topiramate; gabapentin in particular needs further evaluation. Trials designed with sufficient power to compare different drugs are also necessary.