Topiramate Not Superior to Valproate or Placebo in Juvenile Myoclonic Epilepsy

Girl hooked up to EEG machine
This systematic review does not provide sufficient evidence to support topiramate for the treatment of people with juvenile myoclonic epilepsy.

Study results published in the Cochrane Database of Systematic Reviews found little evidence to support the superiority of topiramate over valproate or placebo for managing juvenile myoclonic epilepsy (JME).1

The Cochrane Register of Studies was used to search for ongoing trials, conference proceedings, and randomized controlled trials that compared topiramate with either placebo or another anti-epileptic drug in patients with JME or co-existent primarily generalized tonic-clonic seizures (PGTCS) with electroencephalogram-confirmed JME.

Outcomes of interest included the percentage of responders (ie, ≥50% reduction in seizure frequency from baseline to end of therapy), number of patients who attained seizure-free status, and the percentage of individuals who experienced ≥1 adverse event.

A total of 3 studies consisting of a pooled cohort of 83 participants were included in the systematic review.

In 1 study,2 a higher percentage of patients who received topiramate experienced a ≥50 reduction in PGTCS compared with patients who received placebo (73% vs 18%, respectively; risk ratio [RR] 4.00; 95% CI, 1.08-14.75; P =.04).

The median PGTCS reduction after 20 weeks was 64% in the topiramate group and 38% in the placebo group, which was not significantly different.

An intention-to-treat analysis in another study3 found that a non-significantly lower percentage of patients in the topiramate group had a ≥50 reduction in myoclonic seizures vs patients who took valproate (85% vs 100%, respectively; RR 0.88; 95% CI, 0.67-1.15).

While a higher percentage of patients who took topiramate also had a greater reduction in PGTCS vs patients who received valproate, these findings were also not significant (91% vs 75%, respectively; RR 1.22; 95% CI, 0.68-2.21).

In the third study,4 participants in the topiramate group completed 24-week maintenance therapy, in which 64% (7/11) were seizure-free. Of the 16 participants in the valproate group who completed a 24-week follow-up, only 56% were seizure-free. This was not significantly different (RR 1.13; 95% CI, 0.61-2.11).

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Topiramate was better tolerated,  but no more effective, than valproate based on the information from these trials. Although topiramate seemed to work better than placebo, this result was based on a small number of included people.

Limitations of the included studies were the lack of data on allocation concealment, lack of a double-blind design, and the very low quality of evidence.

“This review does not provide sufficient evidence to support topiramate for the treatment of people with JME,” wrote the researchers. “Well-designed, double-blind, randomized controlled trials with large samples are required to test the efficacy and tolerability of topiramate in people with JME,” they concluded.


1. Liu J, Wang LN, Wang YP. Topiramate for juvenile myoclonic epilepsy [published online January 28, 2019]. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD010008.pub4

2. Biton V, Montouris GD, Ritter F, Riviello JJ, Reife R, Lim P, Pledger G; Topiramate YTC Study Group. A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Neurology. 1999;52(7):1330-1337.

3. Levisohn PM, Holland KD. Topiramate or valproate in patients with juvenile myoclonic epilepsy: a randomized open-label comparison. Epilepsy Behav. 2007;10(4):547-552.

4. Park KM, Kim SH, Nho SK, Shin KJ, Park J, Ha SY, Kim SE. A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy. J Clin Neurosci. 2013;20(8):1079-1082.