HIGH-DOSE GABAPENTIN IN REFRACTORY PARTIAL EPILEPSY - CLINICAL OBSERVATIONS IN 50 PATIENTS

Fifty patients with refractory partial seizures took part in a prospec tive, observational study of adjuvant gabapentin (GBP) in increasing d oses. Thirty-three were started on 400 mg GBP daily with further weekl y increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, trot fully controlled on low dose GBP, followed the same regimen. All patie nts took the drug three times daily. Comparisons were made with seizur e numbers during a 3-month baseline during which antiepileptic medicat ion remained unchanged. Overall, 24 of the 50 patients documented a se izure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nin e appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1.4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, hea dache and diplopia. On GBP doses exceeding 3600 mg daily, three patien ts developed flatulence and diarrhoea and two more had myoclonic jerks . Mean circulating GBP concentrations (mg/l) at each 1200 mg dose leve l were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg-13.2; 4800 mg-15. 5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily , GBP concentrations continued to rise linearly at each dosage increme nt. Although limited, our results do not support the suggestion that G BP absorption is saturable. High dose GBP may be effective in controll ing seizures in patients with refractory partial epilepsy. (C) 1998 El sevier Science B.V.