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Partial-onset Seizures (partial-onset + seizures)

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Medical Sciences	100%

Selected Abstracts

Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset Seizures

EPILEPSIA, Issue 7 2007
Elinor Ben-Menachem
Summary:,Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions. Methods: During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis. Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs. Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED. [source]

A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add-On Therapy to Carbamazepine in Patients with Partial-Onset Seizures

EPILEPSIA, Issue 9 2000
A. P. Aldenkamp
Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil-ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25-mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD). [source]

Eslicarbazepine Acetate: A Double-blind, Add-on, Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset Seizures

EPILEPSIA, Issue 3 2007
Christian Elger
Summary:,Objective: To explore the efficacy and safety of eslicarbazepine acetate (BIA 2-093), a new antiepileptic drug, as adjunctive therapy in adult patients with partial epilepsy. Methods: A multicenter, double-blind, randomized, placebo-controlled study was conducted in 143 refractory patients aged 18,65 years with ,4 partial-onset seizures/month. The study consisted of a 12-week treatment period followed by a 1-week tapering off. Patients were randomly assigned to one of three groups: treatment with eslicarbazepine acetate once daily (QD, n = 50), twice daily (BID, n = 46), or placebo (PL, n = 47). The daily dose was titrated from 400 mg to 800 mg and to 1,200 mg at 4-week intervals. The proportion of responders (patients with a ,50% seizure reduction) was the primary end point. Results: The percentage of responders versus baseline showed a statistically significant difference between QD and PL groups (54% vs. 28%; 90% CI =,,, ,14; p = 0.008). The difference between the BID (41%) and PL did not reach statistical significance (90% CI =,,, ,1; p = 0.12). A significantly higher proportion of responders in weeks 5,8 was found in the QD group than in the BID group (58% vs. 33%, respectively, p = 0.022). At the end of the 12-week treatment, the number of seizure-free patients in the QD and BID groups was 24%, which was significantly different from the PL group. The incidence of adverse events was similar between the treatment groups and no drug-related serious adverse events occurred. Conclusion: Eslicarbazepine acetate was efficacious and well tolerated as an adjunctive therapy of refractory epileptic patients. [source]

Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures

EPILEPSIA, Issue 6 2010
Gregory Krauss
Summary Purpose:, Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200,800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods:, This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2,5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results:, A total of 160 patients received lacosamide 200,800 mg/day, i.v., for 2,5 days, of which 69% received 400,800 mg/day doses. The most common AEs (reported by ,10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (,400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion:, This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2,5 days) replacement for patients temporarily unable to take oral lacosamide. [source]

Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trials

EPILEPSIA, Issue 3 2010
Michael R. Sperling
Summary Purpose:, To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS). Methods:, Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for ,1 year. Therapy-refractory epilepsy patients (,16 years) remained on stable doses of prescribed antiepileptic drugs (,2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ,50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase. Results:, Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16,75 years) and 36 years (study 2, range 16,74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p < 0.01) in both efficacy measures compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did not differ statistically from placebo in either study. Among the most common treatment-emergent adverse events (,5% in any group), those with an incidence exceeding placebo (,3%) were dizziness (400 mg/day group) and somnolence. Conclusions:, Carisbamate 400 mg/day was effective in patients with refractory partial-onset seizures in one of these global studies. More than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well-tolerated in both studies. [source]

Generalized-onset seizures with secondary focal evolution

EPILEPSIA, Issue 7 2009
Randy Williamson
Summary The international seizure classification recognizes that partial-onset seizures can become secondarily generalized, but generalized-onset seizures are expected to remain generalized. We report six patients who had recorded seizures with generalized onset, but subsequent evolution into a focal discharge. The clinical seizure onset was generalized absence or myoclonic, and the most common subsequent clinical pattern was prolonged behavioral arrest with mild automatisms, and then postictal confusion. The ictal discharge started with generalized spike-and-wave activity and then acquired a focal predominance. Interictal epileptiform activity was generalized. There were no focal magnetic resonance imaging abnormalities. Four patients were misdiagnosed with complex partial seizures. All patients were initially refractory, but three became seizure-free and three improved after treatment with antiepileptic medications appropriate for absence or myoclonic seizures. Generalized-onset seizures that acquire focal features are easily misdiagnosed as complex partial. These seizures have a more favorable response to medications effective against generalized absence and myoclonic seizures. [source]

Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial

EPILEPSIA, Issue 3 2009
Péter Halász
Summary Purpose:, To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods:, This multicenter, double-blind, placebo-controlled trial randomized patients (age 16,70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period. Results:, Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose-related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed. Discussion:, Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial-onset seizures in patients with epilepsy. [source]

Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset Seizures

Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to Carbamazepine

EPILEPSIA, Issue 5 2005
Jerzy Majkowski
Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source]

Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label Trial

EPILEPSIA, Issue 5 2002
Tracy A. Glauser
Summary: ,Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures. Methods: Children (aged 6,12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20,40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions. Results: Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence. Conclusions: This open-label study of adjunctive LEV therapy (at 20,40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6,12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings. [source]

Lacosamide as treatment of epileptic seizures , cost utility results for Sweden

ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2010
K. Bolin
Bolin K, Berggren F, Forsgren L. Lacosamide as treatment of epileptic seizures , cost utility results for Sweden. Acta Neurol Scand: 2010: 121: 406,412. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives,,, To calculate cost per additional quality-adjusted life-year (QALY) for lacosamide as adjunctive treatment for patients with uncontrolled partial-onset seizures as compared to no adjunctive treatment. Materials and methods,,, A decision-tree simulation model was constructed to calculate the number of seizures and health-care utilization for treated and untreated with lacosamide, respectively. Prices from 2007 were used for all costs. Results,,, All results were calculated for a 24-, 18-, 12- and 6-months follow-up. The cost per additional QALY was estimated to , 27,641 (24 months). Using a willingness-to-pay threshold for a QALY of , 50,000 the net marginal value of using lacosamide was estimated to about , 850,000 per 1000 patients. Conclusions,,, The estimated cost per QALY gained falls within the range of reported estimates of the willingness-to-pay for an additional QALY. The results imply that lacosamide is cost-effective in the treatment of uncontrolled partial-onset seizures (1 , , 9.6 SEK). [source]

Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010
S. Dupont
Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source]

Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures

ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009
A. Gil-Nagel
Objectives ,,, To evaluate the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures. Material and methods ,,, Double-blind, placebo-controlled, parallel-group, multicenter study consisting of an 8-week baseline period, after which patients were randomized to placebo (n = 87) or once-daily ESL 800 mg (n = 85) or 1200 mg (n = 80). Patients received half dose during 2 weeks preceding a 12-week maintenance period. Results ,,, Seizure frequency over the maintenance period was significantly (P < 0.05) lower than placebo in both ESL groups. Responder rate was 23% (placebo), 35% (800 mg), and 38% (1200 mg). Median relative reduction in seizure frequency was 17% (placebo), 38% (800 mg), and 42% (1200 mg). The most common adverse events (AEs) (>10%) were dizziness, somnolence, headache, and nausea. The majority of AEs were of mild or moderate severity. Conclusions ,,, Once-daily treatment with ESL 800 and 1200 mg was effective and generally well tolerated. [source]

Improved CNS tolerability following conversion from immediate- to extended-release carbamazepine

ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2004
A. D. Miller
Objectives , Tolerability of ,narrow therapeutic ratio' (NTR) antiepileptic drugs may improve with uniform drug delivery. We determined whether conversion from immediate-release carbamazepine (IR-CBZ) to extended-release carbamazepine (ER-CBZ) decreased the incidence of CNS side-effects associated with drug concentration oscillations. Methods , We compared CNS side effects and seizure frequency for patients with partial-onset seizures (n = 61) treated with IR-CBZ for ,1 year with conversion to ER-CBZ for ,1 year. We compared tolerability findings with absorption variability of the formulations. Results , Incidence of CNS side-effects decreased from 49% during IR-CBZ treatment to 20% following conversion to ER-CBZ. Patients also had improved tolerability of high doses (,1200 mg/day) during ER-CBZ treatment. Pharmacokinetic analysis showed absorption and drug concentration were much more variable for the immediate-release formulation. Conclusions , This study suggests that ER-CBZ formulations, with smoother drug delivery and less variable absorption, provide improved CNS tolerability compared with immediate-release formulations. [source]