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


METHODS
Systematic review of published and unpublished randomised controlled trials of add-on treatment with new antiepileptic drugs.


METHODS
20 published and eight unpublished trials representing 3883 patients with refractory partial epilepsy.


METHODS
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.
Department of Neurological Science, University of Liverpool. marjon01@liv.ac.uk
A G
AG
Marson
Z A
ZA
Kadir
D W
DW
Chadwick
D000085:Acetates / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000588:Amines; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000078308:Tiagabine; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use; D020888:Vigabatrin; D000078305:Zonisamide; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D007555:Isoxazoles; D009557:Nipecotic Acids; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D000077213:Lamotrigine; D000078308:Tiagabine