Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study

Purpose: To evaluate the tolerability and safety of gabapentin (GBP) as add -on therapy for seizure control. Methods: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages less than or equal to 1,800 versus >1,800 mg/day, when these doses were required to achieve the most e ffective seizure control. Two analyses of adverse events are presented: tol erability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP l ess than or equal to 1,800 versus >1,800 mg/day. The safety analysis requir ed patients to receive at least one dose of GBP and have a followup contact . Results: A total of 2,216 patients enrolled in this open-label, 16-week stu dy and were evaluable for safety. Of these, 74.0% completed the 16-week stu dy, and 281 met the tolerability criteria. Within these 281 patients, two m utually exclusive groups were compared (a) those reporting adverse events a t only less than or equal to 1,800 mg/day (low dose); and (b) those reporti ng adverse events at only >1,800 mg/day thigh dose). Three adverse events ( asthenia, headache, and dizziness) were observed in a statistically signifi cantly larger number of patients at only the low dose than in the group rep orting these same adverse events at only the high dose, suggesting that pat ients who tolerated GBP at less than or equal to 1,800 mg/day did not exper ience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely w ithdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good fo r 78.5% of all patients. Conclusions: Gabapentin doses >1,800 mg/day were as well tolerated as doses less than or equal to 1,800 mg/day and were not associated with more adver se events.