Purpose: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,000-4,800 mg/day) in patients with medically refractory partial epilepsy.
Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed.
Results: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,400-4,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related.
Conclusions: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.