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

Chaisewikul R, Baillie N, Marson AG

Published Online:

August 10, 2011

No evidence to suggest that calcium antagonists have a useful effect on seizures.

Nearly a third of people with epilepsy become resistant to antiepileptic drugs. These older drugs do not prevent seizures for everyone, and they have adverse effects. A range of new drugs have been tested as 'add-on' treatments to try and improve the results from older drugs. The calcium antagonist drugs flunarizine, nifedipine and nimodipine have been tested in this way. The review of trials found no evidence to show an effect of these drugs on seizures. Adverse effects include dizziness, fatigue and unsteadiness (ataxia).

Abstract (click to read)

Background:

This is an updated version of the original Cochrane review published in The Cochrane Library 2001, Issue 4.

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 (12 May 2011), the Cochrane Central Register of Controlled Trials ((CENTRAL) The Cochrane Library 2011, Issue 2) and MEDLINE (1948 to May 2011).

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:

We included 11 trials with a total of 424 participants. One parallel and seven cross-over trials of flunarizine, two cross-over trials of nimodipine and one cross-over 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 other seven cross-over 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 cross-over 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.

This record should be cited as:

Chaisewikul R, Baillie N, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD002750. DOI: 10.1002/14651858.CD002750

Assessed as up to date:

July 5, 2011

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Primary Review Group:

Epilepsy Group

Health topics:

Neurology > Epilepsy > Drugs for broad populations

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

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