Calcium antagonists as an add-on therapy for drug-resistant epilepsy

Background

Nearly a third of people with epilepsy do not have their seizures controlled with current treatments. Continuous attempts have been made to find new antiepileptic drugs based on increasing knowledge of cellular and molecular biology involved in the genesis of epilepsy and seizures. Therefore calcium antagonists that can alter the effects of calcium on brain cells have been investigated for effect on epileptic seizures.

Objectives

To evaluate the effects of calcium antagonists when used as an add-on therapy for people with drug-resistant epilepsy.

Search strategy

We searched the Cochrane Epilepsy Group's Specialized Register (22 December 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2006) and MEDLINE (January 1966 to December 2006).

Selection criteria

Randomized placebo-controlled add-on trials of any calcium antagonists in people with drug-resistant epilepsy.

Data collection and analysis

Two review authors (Rungsan Chaisewikul and Nick Baillie) independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal and adverse effects. Analyses were by intention-to-treat.

Main results

Eleven trials were included. One parallel and seven crossover trials of flunarizine, two crossover trials of nimodipine and one crossover trial of nifedipine.

For flunarizine, the odds ratio (OR) with 95% confidence intervals (CI) for a 50% or greater reduction in seizure frequency for the parallel trial was 1.64 (95% CI 0.55 to 4.94) indicating a non-significant advantage of flunarizine. We were unable to acquire data for this outcome from the seven crossover trials. The overall OR for treatment withdrawal for flunarizine was 5.83 (95% CI 2.06 to 16.45) indicating individuals were significantly more likely to have flunarizine withdrawn than placebo. No adverse effects were statistically associated with flunarizine.

For nifedipine we were unable to acquire the data we required for our specified outcomes.

For nimodipine, we had data only from the first treatment period from one of the two crossover trials (17 participants). The ORs for a 50% or greater reduction in seizure frequency was 11.34 (95% CI 1.00 to 128.03) and for treatment withdrawal was 2.46 (95% CI 0.22 to 27.75).

Authors' conclusions

Flunarizine may have a weak effect on seizure frequency, but had a significant withdrawal rate probably due to adverse effects, and should not be recommended for use as an add-on treatment. Similarly, there is no convincing evidence to support the use of nifedipine or nimodipine as add-on treatments for epilepsy.