Epilepsy is a disorder in which recurrent seizures are caused by abnormal electrical discharges from the brain. Most seizures can be controlled by a single antiepileptic drug (AED); this approach is known as monotherapy. Unfortunately, some people require more than one antiepileptic drug to control their seizures, especially if these originate from one area of the brain (partial epilepsy), instead of being generalised.
Tiagabine is a newer antiepileptic drug that has been used as an additional AED to monotherapy. This review looks at the evidence about how effective tiagabine is in reducing seizures, as well as the side effects that may be associated with its use.
A search of databases was carried out on 11 November 2013. Six trials were found that included 900 people with partial epilepsy. These trials were all randomised controlled trials (RCTs) that compared the antiepileptic drug topiramate versus a placebo drug or a different AED for a period of up to 24 weeks. By taking all evidence from the trials into account, the review found that tiagabine is effective when used with other drugs to reduce the number of seizures in drug-resistant partial epilepsy. However, adding tiagabine to the usual treatment is associated with an increase in side effects such as dizziness, fatigue, nervousness and tremor.
Trials were assessed with regards to bias and quality, and overall, the quality of evidence for the outcome of seizure reduction was rated as high. The trials included in this review did not examine the long-term effects of topiramate as an add-on treatment. Future research is needed to determine how this drug performs in comparison with other newer antiepileptic drugs.
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.
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.
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.
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.
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.
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.
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.