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New antiepileptic drugs: a systematic review of their efficacy and tolerability

^a Department of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Liverpool L9 1AE

Correspondence to: Dr Marson (marjon01{at}liv.ac.uk).

Abstract

Objectives: To evaluate the efficacy and tolerability of the newly developed antiepileptic drugs gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide in patients with refractory partial epilepsy.
Design: Systematic review of published and unpublished randomised controlled trials of add-on treatment with new antiepileptic drugs.
Subjects: 20 published and eight unpublished trials representing 3883 patients with refractory partial epilepsy.
Main outcome measures: Proportion of patients who (a) showed 50% or greater reduction in frequency of seizures (50% responders) and (b) withdrew from each study for any reason.
Results: Odds ratios (95% confidence intervals) relative to placebo for 50% responders were 2.29 (1.53 to 3.43) for gabapentin, 2.32 (1.47 to 3.68) for lamotrigine, 3.03 (2.01 to 4.58) for tiagabine, 4.22 (2.80 to 6.35) for topiramate, 3.68 (2.45 to 5.51) for vigabatrin, and 2.47 (1.36 to 4.47) for zonisamide. Odds ratios for withdrawal were 1.36 (0.75 to 2.49) for gabapentin, 1.19 (0.79 to 1.79) for lamotrigine, 1.81 (1.21 to 2.70) for tiagabine, 2.42 (1.43 to 4.11) for topiramate, 2.58 (1.26 to 5.27) for vigabatrin, and 5.70 (1.76 to 18.49) for zonisamide. Comparing results for each drug showed that all of the 95% confidence intervals overlapped, indicating that they were not significantly different in terms of efficacy and tolerability.
Conclusions: All six drugs were significantly better than placebo at reducing frequency of seizures. These results do not allow an evidence based choice between these drugs as we have no conclusive indication of differences in efficacy or tolerability.

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