Abstracts

Rationale: About 5% of all epilepsy cases are caused by traumatic brain injury, and seizures caused by traumatic brain injury are often resistant to treatment (Herman, Neurology, 2002; 59:21-26). The purpose of this study was to evaluate the efficacy and safety of add-on pregabalin treatment for partial seizures in patients with post-traumatic epilepsy in clinical trials. Methods: Data were pooled from 6 randomized, double-blind, placebo-controlled trials of add-on pregabalin treatment in patients with partial seizures (dosages: 150-600 mg/d, flexible- or fixed-dosage regimens, BID or TID). Patients were males or females ≥12 years old with a diagnosis of epilepsy with partial seizures, post-traumatic etiology. The percent change from baseline, responder rates, and seizure-freedom rates at endpoint were evaluated in all treatment groups combined vs placebo (all partial seizures considered). Treatment-emergent adverse events (AEs) were also assessed. Results: 203 intent-to-treat patients had a post-traumatic epilepsy etiology (n=25: pregabalin 150 mg/d, 26: pregabalin 300 mg/d, 76: pregabalin 600 mg/d, 11: pregabalin flexible-dosage, 65: placebo). Median age was 42.0 years (range: 16.0-82.0 years). Median baseline seizure rate ranged from 7.8-15.8. For percent change from baseline to endpoint in seizure frequency, the Hodges-Lehman estimate for treatment difference between pregabalin and placebo (-39.9%) favored pregabalin (95% confidence interval: -54.9 to -24.4). The proportion of 50% responders in the pregabalin group (43.5%) was significantly greater compared with placebo (16.9%, P=.0002). Similarly, the proportion of 75% responders in the pregabalin group (18.8%) also favored pregabalin as compared with placebo (6.2%, P=.0125). More patients in the pregabalin group (16.2%) achieved seizure freedom during the last 28-day period compared with patients in the placebo group (5.4%, P=.0504). The most common treatment-emergent AEs for pregabalin were dizziness (31.9%), somnolence (22.5%), ataxia (19.6%), asthenia (13.8%), and accidental injury (12.3%). The most common treatment-emergent AEs for placebo were somnolence (18.5%), dizziness (18.5%), asthenia (15.4%), headache (12.3%), and accidental injury (10.8%). Conclusions: Pregabalin as add-on treatment for partial seizures is an effective and well-tolerated treatment for patients with post-traumatic epilepsy. Study funded by Pfizer Inc.