Topiramate for juvenile myoclonic epilepsy

Background

Juvenile myoclonic epilepsy (JME) is characterized by involuntary (uncontrolled) twitching of muscles in the shoulders and arms after awakening, often starting in childhood.

Study characteristics

We searched scientific databases for clinical trials comparing the antiepileptic medication, topiramate, with placebo (a pretend treatment) or another antiepileptic drug in people with JME. We wanted to evaluate how well topiramate worked and if it had any side effects. The evidence is current to July 2018.

Key results

We included and analyzed three randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 83 participants. Based on the information in these trials, it seems that topiramate is better tolerated than valproate, but is no more effective than valproate. Topiramate seemed to work better than placebo, but this result was based on a small number of included people.

Quality of the evidence

The quality of the evidence from the studies was very low and the results should be interpreted with caution. More randomized controlled trials with large numbers of participants are required to test how effective and well tolerated topiramate is in people with JME. Future trials should be well-designed and double-blinded (where neither the participant nor the researcher know which treatment has been given until after the results have been collected).

Conclusions
This review does not provide sufficient evidence to support topiramate for the treatment of people with JME.

Authors' conclusions: 

We have found no new studies since the last version of this review was published in 2017. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Read the full abstract...
Background: 

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2017.

Objectives: 

To evaluate the efficacy and tolerability of topiramate in the treatment of JME.

Search strategy: 

For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies.

Selection criteria: 

We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs).

Data collection and analysis: 

Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.

Main results: 

We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate and valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS, or becoming seizure-free. Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group.

Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged all three studies to be at low to unclear bias for the remaining risk of bias domains (random sequence, allocation, blinding). We judged the quality of the evidence from the studies to be very low.

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