Abstracts

Rationale: Brivaracetam (BRV), a 4-n-Propyl-Analogon of Levetiracetam, is a novel ligand of the synaptic vesicle protein SV2A with a 10-30 fold higher affinity than levetiracetam (LEV). It penetrates through the blood brain barrier also much faster due to its high lipophility. Furthermore, BRV dose-dependently inhibits voltage-dependent sodium currents and reverses the inhibitory effects of negative modulators on γ-aminobutyric acid- and glycineinduced currents without affecting calcium channels or AMPA receptors. BRV has shown potent suppression of seizure activities in various preclinical and clinical studies. This observational study was performed to evaluate the pragmatic clinical pathways for switching from levetiracetam to brivaracetam in patients with partial onset epilepsy (POE) suffering from nonpsychotic behavioral adverse events (BAEs) during LEV-therapy. Methods: A series of 14 adult patients (aged > 20 yrs.) with difficult-to-treat partial onset epilepsy (POE) suffering from BAEs during add-on-therapy with LEV (1000-3000mg/day) were enrolled.  Switching from LEV to BRV was carried out within an overlapping period up to two weeks. In 2 patients LEV was discontinued because of BAEs before BRV was started. Tapering of LEV was done during the titration of BRV from an initial daily dose of 25mg x2 in the first week to 50mg x2 in the second week by unchanged accompanied anticonvulsive drugs. Seizure frequency and intensity and side effects before and after switching were recorded via the diary by the patient.  Patients were reevaluated after 3 and 6 months in our epilepsy-outpatient department. Results: All 14 patients finished the first observation period of three months. There were no obvious changes of seizure frequency and intensity before and after switching to BRV.  The reported BAEs during LEV including depression, irritability, agitation, aggressive behavior, personality disorder, emotional lability or bipolar disorder were mostly improved in 10 patients, but the depressive symptomatic in the other 4 patients showed no obvious changes within the first three months.  In one patient the partially remained aggressivity after the first three-month therapy might be explained by her newly diagnosed accompanied progressive dementia. Obstipation was reported by one patient under the treatment of BRV. All patient tolerated BRV well. Conclusions: Switching from LEV to BRV with titration during an overlapping period was well tolerated. Most of the patients in the series noted reduced BAEs after switching, which could be due to its more selective mechanism of action of BRV compared to LEV. A different anticonvulsive effectiveness between LEV and BRV was not observed. Therefore in patients suffering from BAEs under LEV as add-on treatment switching to BRV should be considered. Funding: no funding