AUStralian Study of Titration to Effect Profile of Safety (AUS-STEPS): High-dose partial gabapentin (Neurontin) in partial seizures

Purpose:To evaluate the safety, tolerability, efficacy, and impact on quali ty of life of gabapentin (Neurontin GBP) as adjunctive therapy in patients with refractory partial seizures. Methods: AUS-STEPS was an open-label, multicenter, prospective study in pat ients experiencing partial seizures who were inadequately controlled with o ne to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrat ed to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to ac hieve an efficacious and tolerable dosage. Efficacy was assessed by seizure -frequency data. Quality of life was evaluated by using the QOLIE- 10 quest ionnaire, and safety was assessed by adverse-event reports and clinical lab oratory findings. Results: A total of 176 patients received treatment with GBP, with 174 eval uable for intention-to-treat (ITT) efficacy analysis. A reduction of > 50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adve rse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events nece ssitating discontinuation as the dose of GBP was titrated upward. Conclusions. This study indicates that patients with partial epilepsy may b e effectively treated with GBP at dosages of less than or equal to4,800 mg/ day, without altering the safety profile of the drug.