Drug-resistant epilepsy in adults: Outcome trajectories after failure of two medications.

OBJECTIVE: To examine the seizure trajectories of adults with epilepsy developing drug-resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome. METHODS: Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors. RESULTS: Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure-free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow-up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00-14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88-5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53-9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69-81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern. SIGNIFICANCE: Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period.

Comparative efficacy of unique antiepileptic drug regimens in focal epilepsy: An exploratory study.

OBJECTIVE: To compare efficacy of unique antiepileptic drug (AED) polytherapy regimens among patients with focal epilepsy. METHODS: From a longitudinal study of AED treatment, we identified patients with active focal epilepsy who had attempted at least two unique AED regimens (mono-, duo-, or tri-therapy). Efficacy was defined as the presence of at least one six-month period of continuous seizure freedom during exposure to a regimen. To control for individual variations in response and epilepsy severity, we used within-patient comparison approaches, in which we: 1) compared head-to-head unique regimens tried within the same patients; 2) compared one regimen versus aggregate of other regimens attempted in that patient; and 3) compared aggregated monotherapy versus polytherapy regimens. RESULTS: 757 patients met our criteria and had collectively attempted 170 unique regimens. In the head-to-head analysis, lamotrigine monotherapy was more effective than phenytoin monotherapy. Two regimens were more effective than the aggregate of other regimens attempted: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other regimens exhibited slightly better efficacy but did not reach statistical significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine. Patients who previously attempted at least four regimens had slightly better outcomes on polytherapy than monotherapy, though this was not significant. SIGNIFICANCE: We identified two unique regimens more likely to be associated with ≥6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Polytherapy may be an effective alternative to monotherapy for patients with focal epilepsy and persistent seizures.