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Gabapentin add-on for drug-resistant partial epilepsy.

Abstract

BACKGROUND

The majority of 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 partial seizures. In this review we summarise the current evidence regarding the antiepileptic drug gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy.

OBJECTIVES

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

SEARCH METHODS

This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 4. We searched the Cochrane Epilepsy Group's Specialised Register (14 May 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4, The Cochrane Library) (April 2013) and MEDLINE (1946 to 14 May 2013). We imposed no language restrictions.

SELECTION CRITERIA

Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant partial epilepsy. Trials using an active drug control group or which compared doses of gabapentin were also included in the review.

DATA COLLECTION AND ANALYSIS

Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (a) seizure frequency and seizure freedom; (b) treatment withdrawal (any reason); (c) adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best and worst-case analyses. We estimated summary risk ratios for each outcome and evaluated dose-response in regression models.

MAIN RESULTS

Eleven trials were included representing 2125 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for 50% or greater reduction in seizure frequency compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55). Dose regression analysis (for trials in adults) shows increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to 1800 mg of gabapentin 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). Adverse effects were significantly associated with gabapentin compared to placebo. Risk ratios were as follows: ataxia 2.01 (99% CI 0.98 to 4.11), dizziness 2.43 (99% CI 1.44 to 4.12), fatigue 1.95 (99% CI 0.99 to 3.82) and somnolence 1.93 (99% CI 1.22 to 3.06). No significant differences were found for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35) or nausea (RR 0.95, 99% CI 0.52 to 1.73). Overall the studies together are rated as low/unclear risk of bias due to information on each risk of bias domain not being available.

AUTHORS' CONCLUSIONS

Gabapentin has efficacy as an add-on treatment in people with drug-resistant partial 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.

Authors+Show Affiliations

Department of Neurology, Royal Preston Hospital, Preston, UK. sarahalbachari@yahoo.co.uk.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

23888424

Citation

Al-Bachari, Sarah, et al. "Gabapentin Add-on for Drug-resistant Partial Epilepsy." The Cochrane Database of Systematic Reviews, 2013, p. CD001415.
Al-Bachari S, Pulman J, Hutton JL, et al. Gabapentin add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2013.
Al-Bachari, S., Pulman, J., Hutton, J. L., & Marson, A. G. (2013). Gabapentin add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews, (7), CD001415. https://doi.org/10.1002/14651858.CD001415.pub2
Al-Bachari S, et al. Gabapentin Add-on for Drug-resistant Partial Epilepsy. Cochrane Database Syst Rev. 2013 Jul 25;(7)CD001415. PubMed PMID: 23888424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin add-on for drug-resistant partial epilepsy. AU - Al-Bachari,Sarah, AU - Pulman,Jennifer, AU - Hutton,Jane L, AU - Marson,Anthony G, Y1 - 2013/07/25/ PY - 2013/7/27/entrez PY - 2013/7/28/pubmed PY - 2013/12/21/medline SP - CD001415 EP - CD001415 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 7 N2 - BACKGROUND: The majority of 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 partial seizures. In this review we summarise the current evidence regarding the antiepileptic drug gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH METHODS: This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 4. We searched the Cochrane Epilepsy Group's Specialised Register (14 May 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4, The Cochrane Library) (April 2013) and MEDLINE (1946 to 14 May 2013). We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant partial epilepsy. Trials using an active drug control group or which compared doses of gabapentin were also included in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (a) seizure frequency and seizure freedom; (b) treatment withdrawal (any reason); (c) adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best and worst-case analyses. We estimated summary risk ratios for each outcome and evaluated dose-response in regression models. MAIN RESULTS: Eleven trials were included representing 2125 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for 50% or greater reduction in seizure frequency compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55). Dose regression analysis (for trials in adults) shows increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to 1800 mg of gabapentin 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). Adverse effects were significantly associated with gabapentin compared to placebo. Risk ratios were as follows: ataxia 2.01 (99% CI 0.98 to 4.11), dizziness 2.43 (99% CI 1.44 to 4.12), fatigue 1.95 (99% CI 0.99 to 3.82) and somnolence 1.93 (99% CI 1.22 to 3.06). No significant differences were found for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35) or nausea (RR 0.95, 99% CI 0.52 to 1.73). Overall the studies together are rated as low/unclear risk of bias due to information on each risk of bias domain not being available. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant partial 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/23888424/Gabapentin_add_on_for_drug_resistant_partial_epilepsy_ L2 - https://doi.org/10.1002/14651858.CD001415.pub2 DB - PRIME DP - Unbound Medicine ER -