CONVERSION TO HIGH-DOSE GABAPENTIN MONOTHERAPY IN PATIENTS WITH MEDICALLY REFRACTORY PARTIAL EPILEPSY

Purpose: To evaluate the safety and efficacy of high dose gabapentin ( GBP) monotherapy (3,000-4,800 mg/day) in patients with medically refra ctory) partial epilepsy. Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label ph ase of a double-blind, dose-controlled, GBP monotherapy trial. For tho se who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while main tained on the highest daily GBP dose was compared to the seizure frequ ency 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 pat ients participated in the open-label phase of the trial and 23 (51%) w ere converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of foll ow-up was 252 days. Compared to baseline, there was a mean reduction o f 54%, 43%, and 14% for simple partial, complex partial and secondaril y generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosag e (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 frequ ency and total daily GBP dose or with serum levels. High-dose GBP mono therapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepin ess and was not dose-related. Conclusions: GBP monotherapy is well tol erated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.