Elinor Ben-Menachem1, Eric Gilland. 1. Department of Clinical Neuroscience, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden. ebm@neuro.gu.se
Abstract
PROBLEM: Levetiracetam (LEV) is a new antiepileptic drug shown to be effective for the treatment of partial seizures in pivotal clinical trials. We investigated the long-term efficacy and tolerability of LEV as add-on therapy, regardless of seizure type, especially in persons who would not be eligible for clinical trials due to factors such as mental retardation and concomitant psychiatric disorders. METHODS: Ninety-eight patients participated and were followed for 1 year. Demographic data, seizure frequency, and side effects were recorded at baseline and during the 1-year follow-up. The first 35 patients were given LEV at a starting dose of 500 mg b.i.d. with weekly increments of 1000 mg (fast titration). The other patients were given LEV with a starting dose of 250 mg b.i.d. with weekly increments of 250 mg (slow titration). RESULTS: Fourteen patients were completely seizure free after titration to effective dose and 57 were responders with >50% seizure reduction for the first year. In the group with generalized seizures, 1 out of 19 became seizure free, but 8 patients had >50% decrease. Average dose at 1 year was 1900 mg (+/-900). Seventeen of 38 discontinuations were due to adverse effects and 21 were due to lack of efficacy. With fast titration, 15 out of 35 (43%) experienced tiredness during the first 12 weeks, and with slower titration 20 of 63 (32%) experienced tiredness. The difference was not statistically significant. Four out of the five patients who discontinued due to behavioral adverse events (mainly irritability) previously had behavioral problems and/or mental retardation. One patient discontinued due to psychosis. CONCLUSIONS: Levetiracetam appears to be well tolerated in patients with severe epilepsy and shows efficacy in a long-term follow-up. Behavioral adverse events were noted in a small number of patients and occurred mainly in patients who had a history of behavioral disturbance or were mentally retarded. These data from an open population are consistent with the findings of clinical trials.
PROBLEM: Levetiracetam (LEV) is a new antiepileptic drug shown to be effective for the treatment of partial seizures in pivotal clinical trials. We investigated the long-term efficacy and tolerability of LEV as add-on therapy, regardless of seizure type, especially in persons who would not be eligible for clinical trials due to factors such as mental retardation and concomitant psychiatric disorders. METHODS: Ninety-eight patients participated and were followed for 1 year. Demographic data, seizure frequency, and side effects were recorded at baseline and during the 1-year follow-up. The first 35 patients were given LEV at a starting dose of 500 mg b.i.d. with weekly increments of 1000 mg (fast titration). The other patients were given LEV with a starting dose of 250 mg b.i.d. with weekly increments of 250 mg (slow titration). RESULTS: Fourteen patients were completely seizure free after titration to effective dose and 57 were responders with >50% seizure reduction for the first year. In the group with generalized seizures, 1 out of 19 became seizure free, but 8 patients had >50% decrease. Average dose at 1 year was 1900 mg (+/-900). Seventeen of 38 discontinuations were due to adverse effects and 21 were due to lack of efficacy. With fast titration, 15 out of 35 (43%) experienced tiredness during the first 12 weeks, and with slower titration 20 of 63 (32%) experienced tiredness. The difference was not statistically significant. Four out of the five patients who discontinued due to behavioral adverse events (mainly irritability) previously had behavioral problems and/or mental retardation. One patient discontinued due to psychosis. CONCLUSIONS:Levetiracetam appears to be well tolerated in patients with severe epilepsy and shows efficacy in a long-term follow-up. Behavioral adverse events were noted in a small number of patients and occurred mainly in patients who had a history of behavioral disturbance or were mentally retarded. These data from an open population are consistent with the findings of clinical trials.
Authors: Colin B Josephson; Jordan D T Engbers; Nathalie Jette; Scott B Patten; Shaily Singh; Tolulope T Sajobi; Deborah Marshall; Yahya Agha-Khani; Paolo Federico; Aaron Mackie; Sophie Macrodimitris; Brienne McLane; Neelan Pillay; Ruby Sharma; Samuel Wiebe Journal: JAMA Neurol Date: 2019-04-01 Impact factor: 18.302
Authors: Johannes Roland Erath; Jasmin Nicole Nessler; Franziska Riese; Enrice Hünerfauth; Karl Rohn; Andrea Tipold Journal: Front Vet Sci Date: 2020-04-03
Authors: Ciarán Campbell; Mark McCormack; Sonn Patel; Caragh Stapleton; Dheeraj Bobbili; Roland Krause; Chantal Depondt; Graeme J Sills; Bobby P Koeleman; Pasquale Striano; Federico Zara; Josemir W Sander; Holger Lerche; Wolfram S Kunz; Kari Stefansson; Hreinn Stefansson; Colin P Doherty; Erin L Heinzen; Ingrid E Scheffer; David B Goldstein; Terence O'Brien; David Cotter; Samuel F Berkovic; Sanjay M Sisodiya; Norman Delanty; Gianpiero L Cavalleri Journal: Epilepsia Date: 2022-04-01 Impact factor: 6.740