Gabapentin add-on for drug-resistant partial epilepsy

The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding a new antiepileptic drug, gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy.

To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for patients with drug-resistant partial epilepsy.

We searched the Cochrane Epilepsy Group's trial register, the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2000). In addition, we contacted Parke Davis (manufacturers of gabapentin) and experts in the field to seek any ongoing studies or unpublished studies.

Randomized placebo controlled double blind add-on trials of gabapentin in patients with drug-resistant partial epilepsy.

Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios were estimated for each outcome. Dose response was evaluated in regression models, and Number Needed to Treat (NNTs) were calculated for individual doses.

Five trials were included representing 997 randomized patients. Overall odds ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in seizure frequency compared to placebo was 1.93 (1.37 - 2.71). Dose regression analysis shows increasing efficacy with increasing dose, with 28.5% (21.5 - 36.7) of patients responding to 1800mg of gabapentin compared to placebo, NNT 6.7 (3.0 - 10.5). Treatment withdrawal OR (95% CI) compared to placebo 1.05 (0.68 - 1.61); Side effects: OR (99% CI) compared to placebo. Dizziness 2.22 (1.28 - 3. 85); fatigue 2.28 (1.15 - 4.52); somnolence 2.01 (1.24 - 3.28) were significantly associated with gabapentin.

Gabapentin has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.