Patterns of treatment response in newly diagnosed epilepsy

Abstract

Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.

Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: (A) early and sustained seizure freedom; (B) delayed but sustained seizure freedom; (C) fluctuation between periods of seizure freedom and relapse; and (D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year.

Results: A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. 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. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The 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 regimen.

Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.

Figure 1. Patient flow throughout the study in terms of seizure outcome

Seizure-free represents a patient with no seizure for at least the previous 12 months. Pattern A (early and sustained seizure freedom): patients became seizure-free within 6 months of starting treatment and remained seizure-free. Pattern B (delayed and sustained seizure freedom): patients became seizure-free after 6 months of starting treatment and remained seizure-free. Pattern C (fluctuating course): patients fluctuating between periods of seizure freedom and relapse. Pattern D: patients never seizure-free for any complete year.

Figure 2. Cumulative probability of being seizure-free by time from start of treatment and number of antiepileptic drug regimens tried

(A) All patients (n = 1,098; 700 tried 1, 230 tried 2, 100 tried 3, 36 tried 4, and 32 tried 5 or more regimens); (B) patients with idiopathic epilepsies (n = 251; 220 tried 1–2, 31 tried 3 or more regimens); and (C) patients with symptomatic or cryptogenic (nonidiopathic) epilepsies (n = 847; 710 tried 1–2, 137 tried 3 or more regimens).