Abstracts

Rationale: To formulate appropriate pharmacological management of epilepsy, it is important to understand the long-term patterns of response to antiepileptic drugs (AEDs). The goal of this project was to explore the temporal patterns of outcome, to determine the probability of seizure freedom with successive regimens and to identify factors predictive of poorer prognosis in patients with newly diagnosed epilepsy.Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into four patterns: (A) early and sustained seizure freedom; (B) delayed but sustained seizure freedom; (C) fluctuation between periods of seizure freedom and relapse; (D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared and predictive outcome measures were explored. Seizure freedom was defined as no seizures for at least the previous year on an unchanged AED regimen.Results: A total of 1,098 patients were included (median age 32 years, range 9 to 93) in the analysis. At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Just 70 (6%) patients remained controlled on a combination of two or more drugs (67 on duotherapy). Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%) and pattern D in 272 (25%) patients. Pattern C patients had episodes of relapse (149 had one relapse, 17 had 2, 4 had 3, 1 each had 4 or 5) intercalated with periods of seizure freedom. Based on the cohorts followed up for at least the respective number of years, 68% (749/1,098) patients were seizure-free continuously for at least 1 year, and 69% (747/1,086), 61% (461/759) and 52% (188/360) for at least 2, 5 and 10 years, respectively (longest 25 years). There was a higher probability of seizure freedom (p<0.001) in patients receiving one compared to two drug regimens, and two compared to three regimens (Fig. 1). This difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens, but a few did so on their sixth or seventh drug schedule. Patients who received two (p<0.001) and three regimens (p<0.01) had a lower probability of seizure freedom if the first drug failed at higher dosage (Fig. 2). Localization-related epilepsies (p<0.02), younger age at diagnosis (p=0.001) and the presence of psychiatric comorbidities (p=0.004) were associated with poorer prognosis.Conclusions: The majority of adolescents and adults with newly diagnosed epilepsy demonstrated a constant course, whether good or bad, that could usually be predicted early. The remainder had a fluctuating course containing periods of remission and relapse. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third, although a few patients had a sustained response to their 5th, 6th or even 7th schedules. Failure at higher dosage of the first drug predicted poorer long-term outcomes.