Abstracts

Rationale: The FDA-recommended maximum dose for levetiracetam (LEV), a commonly used antiepileptic drug, is 3000mg/day. Limited data exist regarding the efficacy of using AED doses at higher than FDA-approved doses. One small, double-blind, randomized parallel group study suggests that LEV dose of 4000 mg/day may be safe and effective (Betts et al., Seizure 2000; 9: 80-87). We examined the rate of efficacy and intolerable side effects in patients who were "pushed" to higher than FDA dose in attempts to control seizures. Methods: We reviewed the records of 750 adults newly started on LEV at Columbia between 1/1/00 and 1/1/10. We examined the efficacy outcome (defined as ≥12 month seizure freedom) and intolerability (defined as adverse effect [AE] requiring dose decrease) stratified by two types of doses: (1) a HIGH LEV dose (3001-4000mg/day), and (2) a VERY HIGH dose (>4000mg/day). Analysis was done using IBM SPSS Statistics 19. Results: As seen in Figure 1, of 750 adults who newly started LEV, 107 (14.3%) failed the FDA-approved dose and were placed on either HIGH (95 patients) or VERY HIGH (23 patients) doses. Of the 95 patients that tried HIGH dose, 4 out of 80 (5.0%) attained ≥12 month seizure remission. The remaining 15 patients had fewer than 12 months of follow up and were still on HIGH dose at last visit. In those who could tolerate HIGH dose, 4 out of 43 (9.3%) attained ≥12 month seizure remission. Among the 23 patients who tried VERY HIGH dose, 1 out of 20 (5.0%) attained ≥12 month seizure remission. The remaining 3 patients had fewer than 12 months of follow up and were still on VERY HIGH dose at last visit. In those who could tolerate VERY HIGH dose, 1 out of 10 (10.0%) attained ≥12 month seizure remission. Twenty-three patients had used HIGH dose for a period ≥12 months. Three patients had used a VERY HIGH dose for a period ≥12 months. Of note, mean duration of HIGH or VERY HIGH doses was 12.9 months (SD 24.2). The most common intolerable AE on HIGH dose was drowsiness (12.6%) (n=95). The most common intolerable AEs on VERY HIGH dose were psychiatric AEs (13.0%), cognitive AEs (8.7%), and drowsiness (8.7%) (n=23). Among patients who discontinued HIGH dose (n=63), 33.3% discontinued due to intolerability. Among patients who discontinued VERY HIGH dose (n=19), 63.3% discontinued due to intolerability. Conclusions: Our findings suggest that using LEV at higher than FDA-recommended dose can lead to long-term seizure freedom in about 5% of patients who failed the FDA-recommended dose, and about 10% of patients if the patient does not discontinue the high dose for intolerability. At these high doses, sedation, psychiatric and cognitive effects were common.