Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: a multicenter open-label single-arm trial in Korean patients

ObjectiveTo evaluate the efficacy and safety of adjunctive zonisamide (ZNS) therapy in Korean adults with uncontrolled partial epilepsy.MethodsStudy patients had an average of at least one seizure per 4-week (averaged over a 12-week historical baseline) despite the use of one to three antiepileptic drugs. The starting dose of ZNS was 100 mg/day, and was increased to 200 mg/day after 2 weeks. During the 12-week maintenance period, the dose of ZNS was adjusted to 200–400 mg/day based on the physicians’ discretion. The global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated.ResultsA total of 121 patients were enrolled, of which 88 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 59.0%. The ≥50% and ≥75% responder rates were 57.3% and 38.5%, respectively. Seizure freedom over the treatment period was observed in 25 patients, but seizure freedom throughout the 16-week treatment period was attained in only 16 patients. On investigator's GES, 84 patients were considered improved, with 33 patients showing marked improvement. In QOLIE-31 scale, seizure worry improved significantly but emotional well-being deteriorated. Treatment-emergent adverse events (AEs) were reported in 80 patients. The most common AEs were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14.0%), nausea (13.2%), and weight loss (10.7%). Twenty-two patients discontinued the trial due to drug-related AEs.ConclusionsOur results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy, though efficacious, is associated with significant tolerability problems.     

Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group

PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas. CONCLUSIONS: Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.     

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.     

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.     

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.     

Disfluent speech in patients with partial epilepsy: beneficial effect of levetiracetam

PURPOSE: The aim of this study was to evaluate the clinical effects of levetiracetam (LEV) in patients with partial epilepsy and disfluent speech. METHODS: Five consecutive patients with partial epilepsy and disfluent speech resulting from developmental or neurogenic stuttering were enrolled in a 9-week, open-label, prospective study. LEV was given in combination with carbamazepine (CBZ) or phenytoin (PHT) at dosages ranging from 500 to 1500mg twice daily. The severity of stuttering was assessed with the verbal fluency test (VFT), and with the patient global impression of improvement (PGI), at baseline and after 9weeks. Electroencephalography and serum monitoring of CBZ and PHT levels were done before and after the study. Seizure frequency was monitored. RESULTS: After LEV therapy, verbal fluency for all patients, as measured by the VFT, improved from 25% at baseline to 64%, as did the speed of oral reading, from 5 to 23%. On the PGI, all patients rated themselves as better and as having less disfluent speech after LEV therapy. For four patients with incomplete control of their seizures, the seizure count decreased by more than 50% after LEV therapy. The beneficial effect of LEV on verbal disfluency demonstrated on the PGI persisted for the entire period of observation, which ranged from 7 to 11 months. CONCLUSIONS: As an add-on therapy, LEV seems to improve verbal fluency in patients with partial epilepsy and disfluent speech. This effect seems unrelated to the antiepileptic activity of the drug. A placebo-controlled trial of LEV in patients with this kind of verbal disfluency is warranted.     

Levetiracetam during 1-year follow-up in children, adolescents, and young adults with refractory epilepsy

PURPOSE: To evaluate the efficacy and safety of levetiracetam (LEV) in refractory crypto/symptomatic, partial or generalised epilepsy in children, adolescents and young adults. METHODS: We performed a prospective open label add-on study in 99 patients (age 12 months to 32 years, mean 14 years) with partial or generalised, crypto/symptomatic seizures. Levetiracetam was added to no more than two baseline AEDs and the efficacy was rated according to seizure type and frequency. RESULTS: LEV was initiated at the starting dose of 10mg/kg/day with 5-day increments up to 50 mg/kg/day, unless it was not tolerated. Concomitant therapy was generally not modified throughout the study. After a mean follow-up period of 6.7 months (range 3 weeks to 29 months), 11 patients (11.1%) were free of seizures (cryptogenic partial epilepsy, 5; symptomatic partial epilepsy, 6). A more than 75% seizure decrease was found in 14 patients (14.1%) and >50% in 8 (8.1%). Seizures were unchanged in 38 (38.4%), and worsened in 23 (23.2%). Mild and transient adverse side effects were found in 17 patients (17.2%), mostly represented by irritability and drowsiness. CONCLUSION: LEV appears to be well tolerated in children and adolescents with severe epilepsy and seems to be a broad spectrum AED, though in our experience, it was more effective against partial seizures with or without secondarily generalisation. LEV efficacy in other epilepsy syndrome should be evaluated further in homogeneous, more selected patients.     

An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.

BACKGROUND: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population.METHODS: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate. RESULTS: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. CONCLUSION: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.     

Efficacy and safety of levetiracetam in children with partial seizures: an open-label trial

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.     

Effects of levetiracetam as an add-on therapy on cognitive function and quality of life in patients with refractory partial seizures

This study comprised two phases and evaluated the effects of levetiracetam (LEV), as an add-on treatment, on cognitive function and quality of life (QOL) in patients with refractory partial seizures. The short-term phase employed a randomized, double-blind, placebo-controlled design including an 8-week baseline period, 4-week titration interval, and 12-week period at the maximum LEV dose (1500 mg twice daily). The long-term phase was an open-label study in which the maximum LEV dose was administered for another 24 weeks. Neuropsychological tests and the 31-item Quality of Life in Epilepsy (QOLIE-31) inventory were administered at baseline, at the end of the short-term phase, and at the end of the long-term phase. Twenty-four eligible patients entered into the final phase. After short-term LEV treatment, performance time on the Wisconsin Card Sorting Test (WCST) and Delayed Logic Memory significantly improved for the patient group, but not the control group. Subscale scores on the QOLIE-31, including scores on Cognitive Functioning and Social Function, also improved only for the LEV group. At the end of the long-term phase, these improvements were maintained, and both groups performed better in more areas, as measured by the Trail Making Test, WCST, and Delayed Visual Memory in the neuropsychological battery and the QOLIE-31 subscales Overall QOL and Health Status. Thus, as an adjunctive therapy, LEV did not negatively affect and, in a way, improved cognitive function and QOL in patients with medically refractory partial seizures. Some of these improvements may be maintained during long-term treatment.     

The effect of seizure severity on quality of life in epilepsy

Seizure severity is an important aspect of epilepsy. The relationship between seizure severity and quality of life in epilepsy, however, has been incompletely explored. With a data set of 118 women from the baseline phase of a clinical treatment trial, the relationship between seizure severity and aspects of quality of life was evaluated. Two domains of the Quality of Life in Epilepsy-31 (QOLIE-31) correlated highly significantly with seizure severity: Seizure Worry (r=-0.265, P=.004) and Social Functioning (r=-0.280, P=0.002). Two additional domains were significantly correlated: Overall Quality of Life (r=-0.210, P=0.023) and Cognitive (r=-0.209, P=0.024). When the potentially confounding effect of depression, measured by the Beck Depression Inventory, was controlled for, the regression of seizure severity with QOLIE-31 Seizure Worry remained significant (P=0.006, R(2)=0.153), as did the regression with QOLIE-31 Social Functioning (P=0.002, R(2)=0.184) and the regression with QOLIE-31 Cognitive (P=0.037, R(2)=0.30). These findings indicate that severe and potentially injurious seizure behaviors contribute to anxiety and socially avoidant behavior for persons with intractable epilepsy.     

Seizure reduction and quality of life improvements in people with epilepsy

PURPOSE: Previous research suggests that seizure freedom may be necessary to improve health-related quality of life (HRQOL) for epilepsy surgery patients, but little is known regarding the seizure-frequency reduction needed to improve HRQOL among medically treated individuals. METHODS: With data from 134 adults with refractory complex partial seizures participating in a randomized controlled antiepileptic drug (AED) trial, we compared the change in HRQOL across groups having different levels of change in seizure frequency: 100%, 75-99%, 50-74% reduction, and 0-50% increase or decrease. Changes over time within each seizure-reduction group also were assessed. HRQOL was measured by the QOLIE-31, QOLIE-89, and SF-36. RESULTS: Subjects who became seizure free reported significantly more positive change than those who did not on the QOLIE-31 and QOLIE-89 overall scores, the QOLIE-89 mental health, physical health, and epilepsy-targeted composites, as well as the SF-36 mental health summary score. Changes over time in overall QOLIE-31 and QOLIE-89 scores were significantly more positive for subjects who achieved seizure freedom (i.e., 100% reduction in seizure frequency) than for those who did not. No significant change in QOLIE-31 and QOLIE-89 overall scores was observed for subjects who did not achieve seizure freedom. CONCLUSIONS: In this study, HRQOL improvement occurred primarily among patients who achieved complete seizure freedom. Many AED trials use a 50% seizure-frequency reduction criterion as a trial end point, but measurable impacts of this degree of reduction in seizure frequency on HRQOL in this sample were not observed. These results further support striving for seizure freedom as an epilepsy care goal.     

The effect of recurrent seizures on cognitive,behavioral, and quality-of-life outcomes after 12 months of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy

PurposeThe purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy.MethodsSeizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist—90 (SCL-90), and the Quality of Life in Epilepsy—31 (QOLIE-31) were administered at baseline and after 48 weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model.ResultsA group-by-time interaction was identified for the total QOLIE-31 score (p < 0.05) and score on two QOLIE-31 subscales (social function: p < 0.001 and seizure worry: p < 0.001), with a significant improvement over time only present in the SF group (all p < 0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p < 0.01) and number of recognition hits on the California Verbal Learning Test (p < 0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48 weeks (p < 0.01). There was no significant group-by-time interaction for any dimension of the SCL-90.ConclusionRecurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy.     

Clinical predictors in patients with refractory epilepsy exposed to levetiracetam: a single-center study

Objectives –  This aim of the study was to ascertain the importance of clinical parameters on the response to treatment in refractory epilepsy patients on levetiracetam (LEV).
Materials and methods –  We retrospectively evaluated medical records of 132 patients aged 17–78 years with refractory epilepsy (defined as a failure of at least two antiepileptic drugs due to the lack of efficacy) exposed to LEV. We analyzed the response (seizure freedom or continuing LEV) using logistic regression.
Results –  Of 132 patients exposed to LEV, 103 cases continued the drug. Of the discontinuations (29/132), 75% were for lack of efficacy and 25% for tolerability problems. Twenty-three percent of the previously refractory patients achieved seizure freedom for at least 1 year with LEV in combination therapy. The dose of LEV in 80% of seizure-free patients was 1000 mg/day or less. The duration of epilepsy, age and sex were not associated with response to LEV. Seizure freedom was associated with epileptic syndrome or etiology. If no specific syndrome was recognized, there was a significantly greater chance for response compared with temporal lobe epilepsy (OR 20.76; 95% CI 2.12–203.61).
Conclusions –  Our study was based on the careful clinical evaluation of the patients with extensive use of video EEG (50%) and MRI scans (95%). These clinical predictors were evasive in previous studies. This study showed that they are worth pursuing but significantly larger groups of patients need to be investigated to reach significant findings.     

Clinical experience with generic levetiracetam in people with epilepsy

Purpose: To describe the clinical outcomes of a compulsory switch from branded to generic levetiracetam (LEV) among people with epilepsy (PWE) in an outpatient setting. Methods: We conducted a retrospective chart review of 760 unduplicated consecutive adult patients attending a tertiary care epilepsy clinic at Ben Taub General Hospital. On November 1, 2008 hospital policy required all patients receiving branded LEV to be automatically switched to generic LEV. We calculated the proportion of patients switching back to branded LEV and reasons for the switch back. Key Findings: Of the 260 patients (34%) being prescribed LEV (generic and brand name) during the study period, 105 (42.9%) were switched back to brand name LEV by their treating physicians. Reasons for switch back included increase in seizure frequency (19.6% vs. 1.6%; p < 0.0001) and adverse effects (AEs) (3.3%). AEs included headache, fatigue, and aggression. Patient age was associated with switchback when controlling for gender, epilepsy classification, and treatment characteristics [relative risk (RR) 2.44; 95% confidence interval (CI) 2.09–2.84; p < 0.05)]. An increase in seizure frequency subsequent to generic substitution was associated with polytherapy compared to monotherapy (3.225; 1.512–6.880; p < 0.05). Significance: A significant proportion of patients in our cohort on generic LEV required switch back to the branded drug. Careful monitoring is imperative because a compulsory switch from branded to generic LEV may lead to poor clinical outcomes, with risk of AEs and increased seizure frequency.     

Improved quality of life in patients with partial seizures after conversion to oxcarbazepine monotherapy

OBJECTIVE: Quality of life (QOL) was assessed in patients who switched to oxcarbazepine monotherapy because of the lack of efficacy or poor tolerability of their current antiepileptic drug (AED). METHOD: This open-label, single-arm study consisted of patients aged 12 >or= years with partial onset seizures. Oxcarbazepine (8-10mg/kg/day for children, 600 mg/day for adults) was titrated up over 4 weeks while the existing AED was tapered off. QOL was evaluated at baseline and end of study (Week 16) using the validated-in-epilepsy QOLIE-31 questionnaire. RESULTS: For all patients who completed the QOLIE-31 at baseline and completion, a statistically significant improvement was noted for both the composite and multi-item subscale QOL scores (P<0.05 vs baseline). Statistically significant mean percentage improvements of >or=10% from baseline (range=10.8-50.1%) were also noted. Significant improvements were seen in health-related QOL for patients who experienced seizure freedom or >or=50% reductions in seizure frequency with oxcarbazepine monotherapy. CONCLUSIONS: Patients with partial seizures who switched to oxcarbazepine monotherapy showed statistically significant, clinically relevant improvements in QOL.     

High‐dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy

We review our experience with high‐dose intravenous levetiracetam (IV‐LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures—while on chronic antiepileptic drugs—that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV‐LEV of 150 mg/kg/day or greater, with a mean dose of 228 ± 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure‐free in two, ≥80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV‐LEV was well tolerated in all children without complications.     

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.     

An open-label, add-on study of pregabalin in patients with partial seizures: A multicenter trial in Greece

Introduction

Pregabalin efficacy and safety as an adjunctive treatment for partial seizures was evaluated using an open-label, flexible-dose.

Study design

In 98 adults with refractory partial epilepsy taking 1–3 anti-epileptic drugs with ≥2 seizures during an 8-week baseline period.

Methods

Pregabalin was increased to ≤600 mg/day during a 9-week dose optimization period with dosage maintained for 12 additional weeks. Primary endpoint was the percentage change in partial seizure frequency between the 8-week baseline and 12-week observation period.

Results

Pregabalin treatment was associated with a significant reduction in partial seizure frequency: median percent change in partial seizure frequency from baseline to 12 weeks was −33% and −22% in patients with a baseline seizure frequency of ≤3 and >3 per 28 days, respectively. The 50% and 75% responder rates were 41.94% (95% CI: 31.91–51.96) and 30.11% (95% CI: 20.78–39.43), respectively. Nineteen percent of subjects were seizure-free throughout the last 12 weeks. Pregabalin administration resulted in a significant reduction in anxiety (mean reduction in Hospital Anxiety and Depression Scale scores of 1.68 units, 95% CI: −2.60 to −0.76). Most patients were much improved or very much improved on Patient Global Impression of Change (53.8%) and Clinical Global Impression of Change (53.8%). The most frequently self-reported adverse events (AEs) were mild or moderate somnolence (20.4%) and dizziness (5.1%) with a low AE discontinuation rate (5.1%).

Conclusions

The efficacy and side-effect profile of pregabalin were similar to previous pregabalin double-blind, controlled studies. Additionally, pregabalin, as an add-on treatment for partial epilepsy, exhibits significant anti-anxiety properties.     

Factors associated with impaired quality of life in younger and older adults with epilepsy

The purpose of this study is to weigh psychological state, patients' demographics, seizure-related factors, and medical comorbidity in older adults with epilepsy against the same parameters in younger adults in an attempt to identify best quality of life (QoL) predictors. The Quality of Life in Epilepsy Inventory for Adults (QOLIE-31) and the Beck Depression Inventory-II (BDI-II) were completed by 146 patients with localization-related epilepsy. There was no statistical difference in the QOLIE-31 total score between younger and older adults. Best QoL predictors were BDI-II and seizure frequency, with BDI-II providing more than 3 times the impact of seizure frequency. BDI-II also substantively predicted most QOLIE-31 domains. Additionally, epilepsy duration positively correlated with overall QoL only among older adults. In summary, in younger as well as older adult epilepsy patients, depressive symptoms emerge as the strongest predictor of QoL. However, older adults appear to adapt better to their chronic health problem.