Efficacy and tolerability of levetiracetam during 1-year follow-up in patients with refractory epilepsy

AbstractProblem: 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 500mg b.i.d. with weekly increments of 1000mg (fast titration). The other patients were given LEV with a starting dose of 250mg b.i.d. with weekly increments of 250mg (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 1900mg (±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

Onset of efficacy and adverse events during Cenobamate titration period

Cenobamate; Drug-resistant epilepsy; SeizuresCenobamato; Epilepsia resistente a los medicamentos; ConvulsionesCenobamat; Epilèpsia resistent a medicaments; ConvulsionsObjectives Cenobamate is an antiseizure medication (ASM) approved in Europe as adjunctive therapy for adults with inadequately controlled focal seizures. This post hoc analysis reports onset of efficacy and characterizes time to onset, duration, and severity of the most common treatment-emergent adverse events (TEAEs) during cenobamate titration. Materials & Methods Adult patients with uncontrolled focal seizures taking 1 to 3 concomitant ASMs were randomized to receive adjunctive cenobamate or placebo (double-blind studies C013 and C017) or cenobamate (open-label study C021). Outcome assessments included efficacy (median percentage change in seizure frequency and onset [studies C013 and C017]) and safety (onset, duration, and severity of TEAEs [all studies]). Results Onset of efficacy was observed by Weeks 1 to 4 of titration in studies C013 and C017 which used a faster titration schedule than study CO21. In study C013, the median percentage seizure frequency reduction was 36.7% in patients receiving cenobamate versus 16.3% in those taking placebo (p = .002); in study C017, significant differences in seizure frequency emerged in Week 1 and continued throughout titration between all cenobamate groups and placebo (p < .001). The most commonly reported TEAEs were somnolence, dizziness, fatigue, and headache, with first onset of each reported as early as Week 1; however, the majority resolved. Conclusions Reductions in seizure frequency occurred during titration with initial efficacy observed prior to reaching the target dose. These reductions were regarded as clinically meaningful because they may indicate early efficacy at lower doses than previously expected and had a considerable impact on patient quality of life. Long-term treatment with adjunctive cenobamate was generally safe and well-tolerated.The double-blind studies and open-label study were funded by SK Life Science, Inc. (Paramus, NJ, USA). Study data were pooled and analyzed by Angelini S.p.a. Nicole Day, PhD, of MedVal Scientific Information Services, LLC (Princeton, NJ, USA) provided medical writing assistance, funded by Angelini S.p.a. The manuscript was prepared according to the International Society for Medical Publication Professionals' “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (/dL) and ESL 1200 mg QD (/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. SIGNIFICANCE: These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations

Partial Onset Seizure Treatment with Adjunctive Lacosamide in Epileptic Adults: A Review

Summary Epilepsy is a common chronic disorder of the brain and can be seen at all ages with a higher prevalence in developing countries. Adjunctive therapy with antiepileptic drugs (AEDs) is the gold standard in treatment of epilepsy. Lacosamide (LCM) is a novel AED which is approved for adjunctive therapy for the treatment of partial-onset seizures. Recently 3 Phase II/III placebo controlled clinical trials with similar designs were conducted to investigate the efficacy and safety of lacosamide (LCM) administered as adjunctive therapy with other AEDs. Data collected from those studies were pooled, re-analyzed and presented in this review article. Results revealed that LCM is well tolerated and effective in seizure reduction as adjunctive therapy in patients with uncontrolled partial-onset seizures. Key words: Antiepileptic drugs; epileptic adults; lacosamide. Özet Epilepsi sık görülen, kronik, serebral bir hastalıktır ve daha çok gelişmekte olan ülkelerde, her yaştaki bireyde karşımıza çıkabilir. Günümüzde antiepileptik ilaçlar (AEİ) ile adjunktif tedavi epilepsi tedavisinde standart olarak uygulanmaktadır. Lakosamit (LCM) parsiyel başlangıçlı nö-betlerin adjunktif tedavisinde kullanımı için onay almış bir AEİ&apos;tır. Yakın zamanda LCM&apos;in etkililiğini ve güvenliliğini araştırmak amacıyla, diğer AEİ&apos;lar ile beraber adjunktif tedavi olarak LCM&apos;in uygulandığı, benzer tasarımlı, plasebo-kontrollü faz II/III klinik çalışmalar gerçekleştirilmiştir. Bu çalışmalardan elde edilen veriler ile bir veri havuzu oluşturulmuş ve üç çalışmadan toplanan bu veriler yeniden analiz edilmiş ve bu derlemede sunulmaktadır. Sonuçlar LCM&apos;in iyi tolere edildiğini ayrıca kontrolsüz parsiyel başlangıçlı nöbetleri olan hastalarda nöbetlerin görülme sıklığını azalttığını ortaya koymuştur

Vagal Blocking for Obesity Control : a Possible Mechanism-Of-Action

14 September 2016 Erratum to: Vagal Blocking for Obesity Control: a Possible Mechanism-Of-Action Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina P Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen, 2016, 2016. Obesity surgery. In the original article on page 4 the figures are referred to as (Fig. 1b-d) and (Fig. 1e) in the text. The correct reference is (Fig. 1b-e) and (Fig. 1f), respectively. In the original article on page 5 the figures are referred to as (Fig. 3c) and (Fig. 3d) in the text. The correct reference is (Fig. 3c,d) and (Fig. 3e,f), respectively. Peer reviewedPostprin

final safety tolerability and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open label extension of phase iii randomized trials study 307

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