Eslicarbazepine acetate add-on for drug-resistant focal epilepsy

Review question

This review is an update of a review previously published in the Cochrane Library 2011, Issue 12. We reviewed the evidence on the efficacy and safety of eslicarbazepine acetate when used as an add-on treatment for medicine-resistant focal epilepsy.

Background

Eslicarbazepine acetate is an antiepileptic medicine that can be added (called an 'add-on' treatment) along with other medicines to treat people who are taking other antiepileptic medication but continue to have seizures. This drug may be beneficial for people who are taking other antiepileptic medicine but continue to have seizures (fits). This review looked at how well eslicarbazepine acetate worked when used as an add-on treatment and at some of the harms or side effects of the medicine.

Study characteristics

The evidence is current to December 2016. We included five clinical trials with 1799 participants aged 16 to 77 years. The included studies had different treatment periods of 12 to 14 weeks. All five trials were randomized controlled trials, which means that people were randomly divided into groups and compared.

Key results

This review found that eslicarbazepine acetate was effective when used in combination with other medicines to reduce the number of seizures in drug-resistant focal epilepsy. People who took eslicarbazepine acetate were more likely to have no seizures than people who took the placebo (a pretend tablet), but they were more likely to withdraw from eslicarbazepine acetate treatment because of side effects. Side effects associated with eslicarbazepine acetate were dizziness, nausea (feeling sick), somnolence (feeling sleepy), vomiting (being sick) and diplopia (having double vision).

Quality of evidence

Altogether the five trials used good methods, but information was missing from the trials for between 10% and 45% of people taking each medicine in each trial. This missing information may have introduced uncertainty into results so the evidence in this review is of moderate quality. More research is needed to look at the long-term effects of eslicarbazepine acetate and to explore how well it works in children with epilepsy.

Authors' conclusions: 

ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant focal epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.

Read the full abstract...
Background: 

This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.

The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant focal epilepsy.

Objectives: 

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

Search strategy: 

The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies.

Selection criteria: 

Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant focal epilepsy.

Data collection and analysis: 

Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models.

Main results: 

We included five trials (1799 participants) rated at low risk of bias apart from a high risk of attrition bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate due to a high discontinuation rate.

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