Topiramate titration and tolerability

OBJECTIVE: To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onse t seizures, with or without secondary generalization, in a multicenter, dou ble-blind trial. METHODS: After a two-week baseline phase, 188 patients were randomized to e ither a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg /d increments at weekly intervals; n = 95) or to a 100/200 titration schedu le (initial dosage 100 mg/d increased by 100-200 mg/d at weekly intervals; n = 93). The maximum dosage of 400 mg/d was therefore achieved in eight wee ks or three weeks respectively. RESULTS: Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment-emergent adver se events (TEAEs) leading to changes in topiramate therapy (i.e., dosage re ductions, interruptions or discontinuations of therapy) (p = 0.048) and sig nificantly reduced treatment interruptions or withdrawals due to TEAEs (p = 0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic response s were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33%, proportion of patients with greater tha n or equal to 50% seizure reduction was 42% vs. 38%, and proportion of pati ents with no seizures during double-blind treatment was 14% vs. 10%, respec tively. Seizure frequency was substantially reduced from baseline during to piramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the median percen t seizure reduction was 51% and 54%, respectively. CONCLUSIONS: Gradual initiation of topiramate therapy can significantly enh ance patient tolerability without delaying therapeutic response.