Felbamate as an add‐on therapy for refractory partial epilepsy
Abstract
Background
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2014) 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 we have assessed its effects as an add‐on therapy to standard drugs in this review.
Objectives
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add‐on treatment for people with refractory partial‐onset epilepsy.
Search methods
For the latest update we searched the Cochrane Epilepsy Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, up to 20 October 2016. 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 We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.
Selection criteria
Randomised 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 cross‐over design.
Data collection and analysis
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.
Main results
We included four randomised controlled trials with a total of 236 participants. Two trials were parallel design, the third had a two‐period cross‐over design, and the fourth had a three‐period cross‐over design. Two studies were at an unclear risk of bias for random sequence generation and allocation concealment. These two studies did not include any description of their methods for outcome assessment and performance blinding (i.e. participants or 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. Only one study reported 50% or greater reduction in seizure frequency. One study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. One study reported percentage reduction in seizure frequency compared to placebo, but there were no P values. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness.
Authors' conclusions
In view of the methodological deficiencies, limited number of individual studies and differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add‐on therapy in people with refractory partial‐onset epilepsy. A large‐scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.
PICOs
Plain language summary
Felbamate as an add‐on therapy for refractory partial epilepsy
Review question
This review aimed to assess whether felbamate has an impact on people with refractory partial‐onset epilepsy when used with other antiepileptic drugs.
Background
Up to 30% people with epilepsy still suffer epileptic seizures despite the use of multiple treatments. Felbamate is a second‐generation antiepileptic drug. However, it is not clear whether felbamate is efficient when used with other antiepileptic drugs.
Study characteristics
We conducted a review of all available, relevant evidence about the impact of felbamate on epilepsy when used with other antiepileptic drugs. This review examined four randomised controlled trials.
Key results
We found no clear evidence to suggest that felbamate was better than placebo at reducing the seizure frequency of 50% or more, nor reducing seizure frequency. Additionally, there was no clear evidence that participants discontinued taking felbamate for intolerable adverse effects.
Certainty of the evidence
It is important to note that the four trials in this review are small and the quality of the evidence is low. The evidence is current to 20 October 2016.
