Abstract:
Purpose: To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. Methods: Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg-day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Results: Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59percent completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was ≥300 mg-day; over half took ≥450 mg-day. There was a mean reduction in the 28-day seizure rate of 25-40percent, and more than 40percent of all patients had a ≥50percent reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6percent were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Conclusions: Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up. ©2010 International League Against Epilepsy.