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Meta-Analysis
. 2014 Feb 5;2014(2):CD001908.
doi: 10.1002/14651858.CD001908.pub3.

Tiagabine add-on for drug-resistant partial epilepsy

Jennifer Pulman  1 , Jane L Hutton, Anthony G Marson
Affiliations
Meta-Analysis

Tiagabine add-on for drug-resistant partial epilepsy

Jennifer Pulman et al. Cochrane Database Syst Rev. .

Abstract

Background: Epilepsy is a common neurological condition that affects almost 0.5% to 1% of the population. Nearly 30% of people with epilepsy are resistant to currently available drugs. Tiagabine is one of the newer antiepileptic drugs; its effects as an adjunct (add-on) to standard drugs are assessed in this review.

Objectives: To evaluate the effects of add-on treatment with tiagabine on seizures, adverse effects, cognition and quality of life for people with drug-resistant localisation-related seizures.

Search methods: This is an updated version of the original Cochrane review published in 2012 (Issue 5). We searched the Cochrane Epilepsy Group Specialised Register (November 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 10) and MEDLINE (1946 to November 2013). No language restrictions were imposed. We also contacted the manufacturers of tiagabine and experts in the field to seek any ongoing or unpublished studies.

Selection criteria: Randomised placebo-controlled add-on trials of people of any age with localisation-related seizures in which an adequate method of concealment of randomisation was used were included. The studies could be double-blind, single-blind or unblinded and of parallel or cross-over design. They had to have a minimum treatment period of eight weeks. Trials using an active drug control group were also included.

Data collection and analysis: Two review authors independently selected trials for inclusion and extracted data. Disagreements were resolved by discussion. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were performed by intention-to-treat. Worst-case and best-case analyses were calculated for seizure outcomes. Dose response was evaluated in regression models. Risk of bias in each study was assessed by two review authors using the Cochrane 'Risk of bias' tool.

Main results: Four parallel-group and two cross-over group trials were included. The overall risk ratio (RR) with 95% confidence intervals (CIs) for a 50% or greater reduction in seizure frequency (tiagabine vs placebo) was 3.16 (95% CI 1.97 to 5.07). Because of differences in response rates among trials, regression models were unable to provide reliable estimates of response to individual doses. The RR for treatment withdrawal was 1.81 (95% CI 1.25 to 2.62). The 99% CIs for the adverse effects of dizziness, fatigue, nervousness and tremor did not include unity, indicating that they are significantly associated with tiagabine. For cognitive and quality of life outcomes, the limited available data suggested no significant effects on cognition and mood and adjustment. Two of the five studies were judged as having low risk of bias, three studies unclear risk of bias and one study high risk of bias. Overall study quality was rated as high using the GRADE approach.

Authors' conclusions: Tiagabine reduces seizure frequency but is associated with some adverse effects when used as an add-on treatment for people with drug-resistant localisation-related seizures.

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Conflict of interest statement

Prof Marson has received payment for speaking and for attending conferences by Sanofi‐Synthelabo, the current manufacturers of tiagabine, and GSK. In addition, a consortium of pharmaceutical companies (GSK, EISAI, UCB Pharma) funded the National Audit of Seizure Management in Hospitals (NASH) through grants paid to University of Liverpool.

Jennifer Pulman and Jane L Hutton have no conflicts of interest.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 3
Figure 3
Forest plot of comparison: 1 Tiagabine versus placebo control—50% or greater reduction in seizure frequency, outcome: 1.1 Intention‐to‐treat analysis.
Analysis 1.1
Analysis 1.1
Comparison 1 Tiagabine versus placebo control—50% or greater reduction in seizure frequency, Outcome 1 Intention‐to‐treat analysis.
Analysis 1.2
Analysis 1.2
Comparison 1 Tiagabine versus placebo control—50% or greater reduction in seizure frequency, Outcome 2 Worst‐case scenario.
Analysis 1.3
Analysis 1.3
Comparison 1 Tiagabine versus placebo control—50% or greater reduction in seizure frequency, Outcome 3 Best‐case scenario.
Analysis 2.1
Analysis 2.1
Comparison 2 Treatment withdrawal, Outcome 1 Treatment withdrawal.
Analysis 3.1
Analysis 3.1
Comparison 3 Adverse effects, Outcome 1 Ataxia.
Analysis 3.2
Analysis 3.2
Comparison 3 Adverse effects, Outcome 2 Dizziness.
Analysis 3.3
Analysis 3.3
Comparison 3 Adverse effects, Outcome 3 Fatigue.
Analysis 3.4
Analysis 3.4
Comparison 3 Adverse effects, Outcome 4 Nausea.
Analysis 3.5
Analysis 3.5
Comparison 3 Adverse effects, Outcome 5 Somnolence.
Analysis 3.6
Analysis 3.6
Comparison 3 Adverse effects, Outcome 6 Headache.
Analysis 3.7
Analysis 3.7
Comparison 3 Adverse effects, Outcome 7 Infection.
Analysis 3.8
Analysis 3.8
Comparison 3 Adverse effects, Outcome 8 Nervousness.
Analysis 3.9
Analysis 3.9
Comparison 3 Adverse effects, Outcome 9 Tremor.
Analysis 4.1
Analysis 4.1
Comparison 4 Tiagabine versus topiramate, Outcome 1 50% or greater reduction in seizure frequency (ITT).
Analysis 4.2
Analysis 4.2
Comparison 4 Tiagabine versus topiramate, Outcome 2 Treatment withdrawal (ITT).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies excluded from this review

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References to other published versions of this review

    1. Pulman J, Hutton J, Marson A. Tiagabine add‐on for drug‐resistant partial epilepsy. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD001908.pub2] - DOI - PMC - PubMed

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