Abstracts

Rationale: Improved AED efficacy after a drug holiday has been observed in patients admitted for long-term video-EEG. Specifically, seizure interval prolongation (SIP effect) has been observed after the AED(s) withdrawn on admission are reinstated before discharge. This effect has been observed predominantly with carbamazepine. The proposed observational study was designed to investigate the “SIP effect” with new AEDs and determine if there is a relationship between the presence of the “SIP effect” and a history of tolerance to AEDs. Methods: We interviewed patients with refractory epilepsy on the day of admission to the epilepsy monitoring unit (EMU). Seizure history obtained included history of previous AED failure and development of tolerance (loss of AED efficacy after initial benefit). We included patients in the study if they had definite epilepsy and were receiving levetiracetam, lamotrigine, oxcarbazepine or carbamazepine. For these patients, dates of the last two seizures before admission were noted and we recorded all seizures after discharge. We measured the SIP effect as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission. We limited the current analysis to patients who had the AEDs withdrawn on admission reinstated without changes at discharge. Results: A total of 46 patients completed the study. Of these 19 (40 %) patients were on monotherapy, 21 (45 %) patients were on dual therapy, and 6 (15%) patients were taking more than two AEDs. We found a significant prolongation of the seizure interval overall (mean seizure interval prolongation was 18.5 ± 27.3 days). There was also a significant SIP for patients on monotherapy with the new AEDs. The mean SIP was significantly greater (p=0.02) in patients on monotherapy (25.6 ± 23.7 days) than patients taking >2 AEDs (13.9 ± 28.9 days). The mean SIP was also greater in patients with prior history of AED tolerance (23.9 ± 35.9 days) compared to patient with no prior history of AED tolerance (13.5 ± 16.2 days), but the difference did not reach statistical significance. Conclusions: SIP does occur after brief withdrawal of the new AEDs. The SIP effect is likely related to the phenomenon of tolerance, clinically seen as loss of AED therapeutic effect.