Reducing versus stopping antiepileptic medications after temporal lobe surgery

Abstract

ObjectiveTo study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery.MethodsWe reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using Cox-proportional hazard modeling and adjusted for, while comparing longitudinal seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped.ResultsA total of 609 patients (86% adults) were analyzed. Follow-up ranged from 0.5 to 16.7 years. Most (64%) had hippocampal sclerosis. Overall, 229 patients had remained on their same baseline AEDs, while 380 patients stopped (127 cases) or reduced (253 cases) their AEDs. Mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) compared to those seizure-free at last follow-up (1.44 years; P-value 0.03). Whether AEDs were withdrawn 12 or 24 months after surgery, there was a 10–25% higher risk of breakthrough seizures within the subsequent 2 years. However, 70% of patients with seizure recurrence after AED discontinuation reachieved remission, as opposed to 50% of those whose seizures recurred while reducing AEDs (P = 0.0001). Long-term remission rates were similar in both AED discontinuation and “unchanged” groups (82% remission for AEDs withdrawn after 1 year and 90% for AEDs withdrawn after 2 years), while only 65% of patients whose recurrences started during AED reduction achieved a 2-year remission by last follow-up.InterpretationAED withdrawal increases the short-term risk of breakthrough seizures after TLE surgery, and may alter the long-term disease course in some patients.

Changing profiles of pediatric epilepsy surgery candidates over time: A nationwide single‐center experience from 1990 to 2011

“…In that study, early AED withdrawal was thought to unmask surgical failure sooner, but not at the cost of long‐term outcomes. This was recently confirmed in a mainly adult cohort study . The changes in survey responses point toward a trend of earlier AED withdrawal, similar to what we observed in the current study.…”

“…This was recently confirmed in a mainly adult cohort study. 27 The changes in survey responses point toward a trend of earlier AED withdrawal, similar to what we observed in the current study. In contrast to these findings, a study from the pediatric UCLA cohort 13 attributed an increased seizure freedom rate in recently operated children to longer AED use after surgery, as compared to children who underwent surgery in earlier time epochs.…”

Antiepileptic drug withdrawal in medically and surgically treated patients: a meta‐analysis of seizure recurrence and systematic review of its predictors

“… 1 Lee et al ., ; 2 Boshuisen et al ., ; 3 Park et al ., ; 4 Menon et al ., ; 5 Rathore et al ., ; 6 Yardi et al ., ; 7 Berg et al ., .…”

Not all that glitters is gold: A guide to surgical trials in epilepsy

“…The notion that recurrent seizures with AED withdrawal reflect the burden of residual epileptogenicity is further supported by the observation that 70% of patients with seizure recurrence after AED discontinuation reachieved remission in one study of TLE surgery63 as opposed to 50% of those whose seizures recurred while AEDs were simply being reduced: a lower threshold required for triggering recurrence thus translated into more difficulty with reattaining drug responsiveness. No clinical predictors could a priori predict patients whose seizures will recur during AED reduction as opposed to those whose seizures will recur after complete AED discontinuation 63. Similarly, although low seizure frequency, lack of secondary generalization, unilateral preoperative EEG and MRI findings, and lack of need for invasive EEG recordings correlate with early seizure freedom after surgery for TLE,46, 53 only the presence of a specific pathological diagnosis predicts long‐term seizure freedom: 40% of patients with gliosis or nonspecific pathology were seizure free 10 years after TLE surgery in the one series that investigated early versus late outcomes independently, as opposed to 80% of those with a specific pathological abnormality 46.…”

“…No randomized clinical trials adequately evaluated AED management after surgery, so the true “risk” of a breakthrough seizure due to AED withdrawal is unknown. However, observational data suggest that, although 17–25% of postoperative seizure recurrences occur with AED withdrawal, seizure control is regained after reinitiation of AEDs in 60–70% of these cases 63, 64, 65. In that group of “seizure free but only while on AEDs,” surgery converted DRE to a pharmacoresponsive disease.…”