Felbamate as an add-on therapy for refractory epilepsy

This review is an update of a previously published review in The Cochrane Database of Systematic Reviews (Issue 1, 2011) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and its effects as an add-on therapy to standard drugs are assessed in this review.

To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with refractory partial-onset epilepsy.

We searched the Cochrane Epilepsy Group Specialized Register (24 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), and PubMed (24 July 2013). This search was run for the original review on 20 May 2010. There were no language and time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.

Randomized placebo-controlled add-on studies of people of any age with refractory partial-onset seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel or crossover design.

Two review authors independently selected studies for inclusion and extracted information. We resolved disagreements by discussion. If disagreements persisted, the third review author arbitrated. We assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.

Three randomised controlled trials with a total of 153 participants were included. The first was a parallel design, the second had a two-period crossover design, and the third had a three-period crossover design. One study was at unclear risk of bias for random sequence generation and allocation concealment. And in the same study, there was no description of how to blind outcome assessment, performance blinding was for participants, might not be for doctors. Two studies were at high risk of bias for incomplete outcome data. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the results. None of the three studies reported 50% or greater reduction in seizure frequency. Only one study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness.

In view of the methodological deficiencies, limited number of individual studies and differences in outcome measure, we have found no reliable evidence to support the use of felbamate as an add-on therapy in patients with refractory partial-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.Since the last version of this review no new studies have been found.