Tiagabine add-on for drug-resistant partial epilepsy.
Author(s): Pulman J(1), Hutton JL, Marson AG.
Affiliation(s): Author information:
(1)Department of Molecular and Clinical Pharmacology, Institute of Translational
Medicine, University of Liverpool, Clinical Sciences Centre for Research and
Education, Lower Lane, Fazakerley, Liverpool, Merseyside, UK, L9 7LJ.
Publication date & source: 2014, Cochrane Database Syst Rev. , 2:CD001908
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experts in the field to seek any ongoing or unpublished studies.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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