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Felbamate add‐on therapy for drug‐resistant focal epilepsy
Shi, Li Li Bresnahan, Rebecca Martin-McGill, Kirsty J. Dong, JianCheng Ni, HengJian Geng, JinSong
Shi, Li Li
Bresnahan, Rebecca
Martin-McGill, Kirsty J.
Dong, JianCheng
Ni, HengJian
Geng, JinSong
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2019-08-01
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Abstract
This is an updated version of the Cochrane Review previously published in 2017.
Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to
30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require
treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug
that can be used as add-on therapy to standard antiepileptic drugs.
Objectives
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for
people with drug-resistant focal-onset epilepsy.
Search methods
For the latest update we searched the Cochrane Register of Studies (CRS Web), MEDLINE, ClinicalTrials.gov and
the WHO International Clinical Trials Registry Platform (ICTRP), on 18 December 2018. There were no language or
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unpublished or ongoing studies.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
We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal
seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or crossover design.
Data collection and analysis
Two review authors independently selected studies for inclusion and extracted information. In the case of
disagreements, the third review author arbitrated. Review authors 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, representing a total of 236 participants, in the review. Two trials
had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period
cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the
incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and
from participants having unstable drug regimens during experimental treatment in one trial. Due to significant
methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to
perform a meta-analysis of the extracted data.
Only one study reported the outcome, 50% or greater reduction in seizure frequency, whilst three studies
reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure
reduction of 35.8% with add-on felbamate while another study claimed a more modest reduction of 4.2%. Both
studies reported that seizure frequency increased with add-on placebo and that there was a significant difference
in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study
reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between
treatments was not significant. There were conflicting results regarding treatment withdrawal. One study
reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies
reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment
withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%),
suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew
from treatment due to adverse effects. The adverse effects consistently reported by all four studies were:
headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated
participants versus 3% to 15% of placebo-treated participants.
We assessed the evidence for all outcomes using GRADE and found it as being very-low certainty, meaning that
we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the
narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could
likely be significantly different from that reported in this current review update.
Authors' conclusions
In view of the methodological deficiencies, the limited number of included studies and the differences in
outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in
people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a
longer period of time is required to inform clinical practice.
Citation
Shi, L.L., Bresnahan, R., Martin‐McGill, K. J., Dong, J., Ni, H., & Geng, J. (2022). Felbamate add‐on therapy for drug‐resistant focal epilepsy. Cochrane Database of Systematic Reviews 2019, Issue 8. Art. No.: CD008295. https://doi.org/10.1002/14651858.CD008295.pub5.
Publisher
Wiley
Journal
Cochrane Database of Systematic Reviews
Research Unit
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1469-493X