Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.     

Conversion to High Dose Gabapentin Monotherapy in Patients with Medically Refractory Partial Epilepsy

Summary: Purpose: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,0004,800 mg/ day) in patients with medically refractory partial epilepsy.
Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed.
Results: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,4004,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related.
Conclusions: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.     

Pregabalin for the management of partial epilepsy

Pregabalin is one of the latest antiepileptic drugs introduced for the treatment of partial epilepsy. Its efficacy and safety as adjunctive therapy in refractory partial epilepsy have been established in four double-blind placebo-controlled trials (n = 1396) and 4 long-term open-label studies (n = 1480). In 3 fixed-dose trials, the proportion of patients with a ≥50% reduction in seizure frequency across the effective dose-range (150–600 mg/day) ranged between 14% and 51%, with a clear dose-response relationship. Suppression of seizure activity could be demonstrated as early as day 2. The most frequently reported CNS-related adverse events included dizziness, somnolence, ataxia and fatigue, were usually mild or moderate, and tended to be dose related. In long-term studies, weight gain was reported as an adverse event by 24% of patients. When pregabalin dose was individualized to according to response within the 150 to 600 mg/day dose range, tolerability was considerably improved compared with use of a high-dose, fixed-dose regimen (600 mg/day) without titration. In long-term studies up to 4 years, no evidence of loss efficacy was identified. During the last year on pregabalin, 3.7% of patients were seizure-free. Pregabalin appears to be a useful addition to the therapeutic armamentariun for the management of refractory partial epilepsy.     

Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy

PURPOSE: A pilot study of the safety, tolerability, dose range and potential efficacy of ganaxolone for the treatment of refractory epilepsy in pediatric and adolescent subjects. METHODS: We report the results of a nonrandomized, nonblinded, open-label, dose-escalation trial of ganaxolone in pediatric subjects (5-15 years) suffering from refractory epilepsy. Subjects received an oral suspension of ganaxolone in a 1:1 complex with beta-cyclodextrin in a dose escalation (1 mg/kg, b.i.d. to 12 mg/kg t.i.d.) schedule over 16 days. This was followed by a maintenance period for 8 weeks. Subjects that showed significant response were eligible for a compassionate use extension period. RESULTS: Fifteen subjects enrolled, eight completed the trial and three continued in the open-label compassionate-use extension period. All subject exhibited refractory partial or generalized epilepsy. In an intent-to-treat analysis, four (25%) were considered substantial responders (>or=50% reduction in seizure frequency), two (13%) were considered moderate responders (between 25 and 50% reduction in seizure frequency) and the remainder were considered nonresponders (<24% reduction). Three subjects entered the extension phase, one remained essentially seizure-free for over 3.5 years of ganaxolone administration. Ganaxolone was tolerated well. A total of 17 adverse events were reported in 10 patients, all were considered mild to moderate in severity. Somnolence was the most frequently (nine) reported adverse event. CONCLUSIONS: This pilot study is consistent with other clinical studies indicating that ganaxolone has anticonvulsant activity in humans. The results of this study encourage the further study of ganaxolone as an antiepileptic therapy.     

Oxcarbazepine reduces seizure frequency in a high proportion of patients with both newly diagnosed and refractory partial seizures in clinical practice.

The antiepileptic efficacy and tolerability of oxcarbazepine, used both as monotherapy and adjunctive therapy, were observed for 1 year in 202 adult patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy in clinical practice in Italy. At first observation, the seizure free rate was 72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom oxcarbazepine replaced another monotherapy and 10.3% in patients given oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the duration of treatment (p < 0.0001). In the 160 completers the seizure free rate was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients reported adverse effects, mainly sedation and sleepiness; 5% discontinued oxcarbazepine because of adverse events. OXC is an effective and well-tolerated antiepileptic agent for the long-term treatment of partial epilepsy in adults.     

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.     

The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy

The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study aimed to evaluate the safety and efficacy of levetiracetam (Keppra, LEV) as add-on therapy for refractory partial seizures in clinical practice. This Phase IV, 16-week, open-label study recruited patients > or =16-year old with treatment-resistant partial seizures. LEV (1000 mg/day) was added to a stable concomitant antiepileptic drug regimen. LEV dosage was adjusted based on seizure control and tolerability to a maximum of 3000 mg/day. 1541 patients (intent-to-treat population) were recruited including 1346 (87.3%) who completed the study and 77.0% who declared further continuing on LEV after the trial. Overall, 50.5% of patients reported at least one adverse event that was considered related to LEV treatment. The most frequently reported drug-related adverse events were mild-to-moderate somnolence, fatigue, dizziness and headache. Serious adverse events considered related to LEV occurred in 1.0% of patients. 7.5% of patients reported adverse events as the most important reason for study drug discontinuation. The median reduction from baseline in the frequency of all seizures was 50.2%; 15.8% of patients were seizure free; 50.1% had seizure frequency reduction of > or =50%. At the end of the study, 60.4% of patients were considered by the investigator to show marked or moderate improvement. There was a significant improvement in health-related quality of life as assessed with the QOLIE-10-P (total score increasing from 55.6 to 61.6; p<0.001). This community-based study suggests that LEV is well tolerated and effective as add-on therapy for refractory partial seizures in adults. These data provide supportive evidence for the safety and efficacy of LEV demonstrated in the pivotal Phase III placebo-controlled studies.     

Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study--the open-label continuation phase of several short-term clinical trials--was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults.     

左乙拉西坦治疗难治性癫痫48例的临床研究

目的：探讨左乙拉西坦（Lev）添加剂量治疗难治性癫痫的疗效和安全性。方法：采用开放性自身对照方法,对48例（儿童23例,成人25例）难治性癫痫患者进行Lev添加治疗,并随访1年以上,收集治疗后患者发作频率变化、无发作情况、不良反应以及退出原因。结果：Lev治疗难治性癫痫总有效率为64．58％,成人有效率高于儿童,对部分性癫痫综合征有效率高;3、6和12个月无发作率分别为6．25％、18．75％和16．67％,保留率为81．25％、56．25％和43．75％。总不良反应发生率为39．58％,无严重不良反应,退出的最主要原因为对疗效欠满意。结论：LEV是一种安全有效的难治性癫痫治疗药物,对部分性和全面性癫痫发作均有效。     

Practical prescribing and long-term efficacy and safety of zonisamide

Long-term efficacy, tolerability and safety of antiepileptic drug (AED) therapy is essential given the chronic nature of epilepsy. Zonisamide (Zonegran), a novel AED with a broad range of mechanisms of action contributing to its antiseizure efficacy, has been evaluated extensively for the long-term management of epilepsy. Open-label extension studies in the United States and Europe suggest continued efficacy of zonisamide in long-term treatment without development of adverse events further to those seen in registration studies. Baseline seizure frequency is reduced by approximately 40-70% during long-term treatment for up to 2 years, and 30-50% of patients attain >or=50% reduction in seizure frequency across all categories of seizure and durations of treatment. Preliminary data indicate a progressive decline in seizure frequency with continued zonisamide treatment. Zonisamide is well tolerated in long-term use, with a trend towards decreasing incidence of generally mild adverse events over time and a low rate of withdrawal during chronic use. Nephrolithiasis and other serious adverse events are infrequent, and can be minimised by appropriate management and patient education. This profile of maintained efficacy, tolerability and safety during sustained administration in combination with other AEDs supports zonisamide as a valuable adjunctive agent in the long-term management of refractory partial epilepsy.     

Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy

PURPOSE: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy. METHODS: This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline. RESULTS: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems. CONCLUSIONS: OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.     

AUStralian Study of Titration to Effect Profile of Safety (AUS-STEPS): High-Dose Gabapentin (Neurontin) in Partial Seizures

PURPOSE: To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures. METHODS: AUS-STEPS was an open-label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure-frequency data. Quality of life was evaluated by using the QOLIE-10 questionnaire, and safety was assessed by adverse-event reports and clinical laboratory findings. RESULTS: A total of 176 patients received treatment with GBP, with 174 evaluable for intention-to-treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward. CONCLUSIONS: This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of < or =4,800 mg/day, without altering the safety profile of the drug.     

Levetiracetam in patients with refractory epilepsy: results of the SKATE trial in Austria, Germany and Switzerland.

PURPOSE: To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization. METHODS: In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period. RESULTS: Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures. CONCLUSION: Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.     

Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy

PURPOSE: This randomised, double-blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy. METHODS: Patients with partial seizures with and/or without secondary generalization or primary generalized tonic-clonic seizures were randomized to either GBP or LTG. During 2- and 6-week titration periods, respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the subsequent 24-week maintenance phase, the dose could be adjusted based on seizure control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300 mg/day for LTG. The primary end point was time to exit, a composite of efficacy and tolerability. Evaluable patients were used for the primary efficacy analysis, whereas tolerability was examined on an intent-to-treat basis. RESULTS: A total of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the evaluable population. Nineteen patients in each group had an exit event. The median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was estimated as 1.043 (90% confidence intervals, 0.602-1.809). Overall, 106 (71.6% of the evaluable population) GBP-treated and 96 (67.1%) LTG-treated patients completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%) taking LTG remained seizure free during the final 12 weeks of treatment. Only 14 (8.9%) GBP-treated patients and 15 (9.9%) LTG-treated patients withdrew because of study drug-related adverse events. CONCLUSIONS: GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.     

Comparison of oxcarbazepine and carbamazepine: a double-blind study

The antiepileptic efficacy and side-effects of oxcarbazepine (OXC), a new carbamazepine derivate, were evaluated in a double-blind study. Forty ambulatory epileptics with unsatisfactory seizure control or unwanted effects due to phenytoin monotherapy were changed to OXC or carbamazepine (CBZ) and were then followed for 48-50 weeks. Thirty-four of the patients completed the study. The seizure frequencies on the trial drugs were not significantly different and the antiepileptic efficacy of OXC was comparable to CBZ. The incidence of side-effects during the initiation phase was lower with OXC suggesting better tolerability of OXC compared to CBZ.     

Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy

Objectives –  To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice.
Materials and methods –  Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice.
Results –  An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom.
Conclusions –  Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy.     

Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures

PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue. CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.     

Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome

PURPOSE: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox-Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS. METHODS: A six-center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures. RESULTS: Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data-collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study. CONCLUSIONS: VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.     

Levetiracetam in a broad population of patients with refractory epilepsy: interim results of the international SKATE trial

OBJECTIVE: To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting. PATIENTS AND METHODS: In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE). RESULTS: Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness. CONCLUSION: Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.