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Meta-Analysis
. 2018 Oct 24;10(10):CD001415.
doi: 10.1002/14651858.CD001415.pub3.

Gabapentin add-on treatment for drug-resistant focal epilepsy

Mariangela Panebianco  1 , Sarah Al-Bachari, Jennifer Weston, Jane L Hutton, Anthony G Marson
Affiliations
Meta-Analysis

Gabapentin add-on treatment for drug-resistant focal epilepsy

Mariangela Panebianco et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: This is an updated version of the Cochrane Review previously published in 2013.Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy.

Objectives: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy.

Search methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web, 20 March 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 March 2018), ClinicalTrials.gov (20 March 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 20 March 2018). We imposed no language restrictions.

Selection criteria: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin.

Data collection and analysis: For this update, two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models.

Main results: We included 12 trials representing 2607 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall RR for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 trials, 1206 participants; moderate-quality evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-quality evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-quality evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-quality evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-quality evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-quality evidence). There were no significant differences for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-quality evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-quality evidence). Overall, the studies were rated at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall quality of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals.

Authors' conclusions: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types.

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Conflict of interest statement

SB: none known.

JW: none known.

MP: none known.

JLH: none known.

AGM: a consortium of pharmaceutical companies (GSK, EISAI, UCB Pharma) funded the National Audit of Seizure Management in Hospitals (NASH) through grants paid to the University of Liverpool. Professor Tony Marson is part funded by National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care North West Coast (NIHR CLAHRC NWC).

Figures

1
1
Study flow diagram. Date of search 20 March 2018. RCT: randomised controlled trial.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Gabapentin versus placebo, outcome: 1.1 Reduction in seizure frequency ≥ 50%.
1.1
1.1. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 1 Reduction in seizure frequency ≥ 50%.
1.2
1.2. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 2 Treatment withdrawal.
1.3
1.3. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 3 Adverse effects.
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References

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