Quality of life and treatment satisfaction in Spanish epilepsy patients on monotherapy with lamotrigine or valproic acid

BackgroundPatients suffering from epilepsy have an impaired health related quality of life (HRQoL) because of seizures and treatment adverse events. Epilepsy affects differently both genders, due to hormonal influence in women. The aim of this study is to assess the impact on HRQoL and treatment satisfaction in epilepsy patients treated with stable doses of lamotrigine and valproic acid.MethodsObservational cohort prospective study was conducted in 18 Spanish neurology sites. Patients with clinically stable partial or generalized epilepsy, already receiving lamotrigine or valproic acid on monotherapy, were assessed in two visits: baseline and at 6 months. Socio-demographic and clinical variables were recorded at baseline; HRQoL (QOLIE-10) treatment satisfaction and women image self-perception were assessed at both visits. Impact on HRQoL was assessed in both treatment arms overall and in the women subgroup.ResultsA total of 107 patients were evaluated; 53 (14 men, 39 women) on lamotrigine and 54 (27 men, 27 women) on valproic acid. Mean (SD) age was 30.4 (9.1) years and mean (SD) time since epilepsy diagnosis was 8 (8.1) years. Mean (SD) QOLIE-10 score at baseline was 73.9 (15.7) points (76.6 and 71.4 for lamotrigine and valproic, respectively). At follow up, patients reported better HRQoL on both lamotrigine (78.8 points) (p < 0.05) and on valproic (72.4 points) in comparison with baseline. Women's HRQoL at follow up was better on the lamotrigine arm compared with valproic acid: 78.8 (12.8) vs. 70.3 (15.9) (p < 0.05). Women on the lamotrigine arm declared higher satisfaction with treatment and higher disagreement with the different statements referred to a negative image self-perception.ConclusionsChronic patients with epilepsy already treated with lamotrigine slightly improved HRQoL at 6 month follow up, whereas no significant changes were observed in the valproic acid group. Lamotrigine impact on patients’ HRQoL seems to be even more positive in the subgroup of women.     

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.     

PatientsLikeMe® Online Epilepsy Community: Patient characteristics and predictors of poor health-related quality of life

ObjectiveThe online PatientsLikeMe® Epilepsy Community allows patients with epilepsy to record, monitor, and share their demographic, disease, and treatment characteristics, providing valuable insights into patient perceptions and understanding of epilepsy. The objective of this retrospective analysis was to characterize the profile of users and their disease and identify factors predictive of poor health-related quality of life (HRQoL), while assessing the platform's potential in providing patient-reported data for research purposes.MethodsData recorded (January 2010–November 2011) by Epilepsy Community members, with an epilepsy diagnosis and who reported > 1 seizure, included the following: sociodemographic and disease characteristics, treatments, symptoms, side effects perceived as medication-related, seizure occurrence, and standardized questionnaires (Quality of Life in Epilepsy Inventory [QOLIE-31/P], EuroQoL 5-Dimensions Scale, 3 Levels [EQ-5D-3L], and Hospital Anxiety and Depression Scale [HADS]). Univariate and multivariate logistic regressions were conducted to identify predictors of poor HRQoL.ResultsDuring the study period, the Epilepsy Community comprised 3073 patients, of whom 71.5% were female, had a mean age of 37.8 years, and had a mean epilepsy duration of 17.7 years. The most frequently reported moderate/severe symptoms (n = 2135) included memory problems (60.2%), problems concentrating (53.8%), and fatigue (50.0%). Medication-related side effects (n = 639) included somnolence (23.2%), fatigue (17.2%), and memory impairment (13.8%). The QOLIE-31/P scores (n = 1121) were significantly worse in patients who experienced a recent seizure. For QOLIE-31/P, highly predictive factors for poor HRQoL included the following: mild/moderate problems concentrating, depression, memory problems, treatment side effects, occurrence of tonic–clonic seizures, and epilepsy duration ≤ 1 year. For EQ-5D-3L, highly predictive factors for poor HRQoL included the following: pain, depression, and comorbidities. Patients on newer AEDs were less likely to report poor HRQoL (QOLIE-31/P).SignificanceThese findings move further towards supporting the feasibility and usefulness of collecting real-world, anonymized data recorded by patients online. The data provide insights into factors impacting HRQoL, suggesting that a holistic treatment approach beyond seizure control should be considered in epilepsy.     

Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled,post-hoc analysis

PurposeThe effect of adjunctive brivaracetam on health-related quality of life (HRQoL) was assessed in a post-hoc analysis using pooled data from three randomized, double-blind, placebo-controlled Phase III studies in patients with refractory focal seizures (NCT00490035, NCT00464269, and NCT01261325).MethodsThe Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P) was completed at randomization, and weeks 4, 8 (in two of three studies), and 12 (end of the treatment period). Mean change from baseline to week 12 or early discontinuation, and percentage of patients with clinically meaningful improvement were reported for the placebo and brivaracetam 50, 100, and 200 mg/day groups.ResultsAt baseline, mean QOLIE-31-P scores were similar between treatment groups. At week 12 or early discontinuation, mean (standard deviation) changes from baseline in QOLIE-31-P total score were 2.8 (12.7), 3.0 (14.0), 2.4 (14.0), and 3.0 (12.1) points for the placebo and brivaracetam 50, 100, and 200 mg/day groups, respectively, indicating HRQoL improved slightly over time during the treatment period, but was similar for placebo and brivaracetam groups. All subscale score changes were positive, indicating stable or improved HRQoL over time. The brivaracetam 100 and 200 mg/day groups showed the largest differences compared with placebo in Seizure Worry subscale scores (7.3 and 8.8 vs. 5.0 points). Approximately 40% of patients had improvements in QOLIE-31-P scores beyond the Minimal Important Change (MIC) thresholds. The subgroup of ≥ 50% focal seizure frequency responders had higher improvements for all treatment arms and all subscales than for those in the overall pooled population.ConclusionIn this post-hoc analysis, adjunctive brivaracetam treatment was shown to be associated with stable or improving overall HRQoL over time, similar to placebo, with modest improvements in subscales sensitive to efficacy, and no deterioration in subscales sensitive to tolerability. These results reflect the known efficacy and tolerability profile of brivaracetam.     

Psychometric evaluation of the Serbian version of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31)

PurposeTo evaluate the psychometric properties of the Serbian-language version of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).MethodsAfter undergoing a translation and cultural adaptation of its items in order to create a Serbian-language version of QOLIE-31, we assessed its psychometric properties—reliability, construct validity and criterion validity. The sample consisted of 203 adults with epilepsy. Reliability was tested both by assessing the internal consistency and by the test–retest method. Construct validity was assessed by factor analysis, multitrait-scaling analysis and method of known-groups validation. This was achieved by assessing the relationship between scales and external measures (socio-demographic characteristics, seizure severity and etiology of epilepsy). Criterion validity was assessed by correlation analysis between QOLIE-31 and Short form 36 health survey (SF-36) and Neurotoxicity scale-II.ResultsThe domains showed high internal consistency (Cronbach's α 0.94). Test–retest reliability for Overall test score was 0.83 (Pearson's coefficient) indicating temporal stability. Seizure severity and etiology of epilepsy significantly influenced all QOLIE-31 domains except the Medication effect domain, with lowest scores in high seizure severity and symptomatic etiology groups. Employment status significantly influenced Overall quality of life, Emotional well-being, Social function and Overall score. Educational level was related to the Emotional well-being domain, with highest scores for students. The QOLIE-31 was highly positively correlated with SF-36 (rho = 0.898) and strongly negatively correlated with Neurotoxicity scale-II (rho = ?0.783).ConclusionSerbian adaptation of the QOLIE-31 questionnaire is reliable and valid for assessing the quality of life in patients with epilepsy.     

Health-related quality of life in Russian adults with epilepsy: The effect of socio-demographic and clinical factors

ObjectiveThe aim of this study was to evaluate socio-demographic and clinical factors influencing the health-related quality of life (HRQOL) of adult patients with epilepsy in a naturalistic treatment setting in Russia.MethodsThe QOLIE-31 questionnaire and the Beck Depression Inventory (BDI) were completed by 208 patients with a broad clinical spectrum of epilepsy (the mean age was 31.49 ± 13.20 years and ranged from 18 to 74 years).ResultsIn Russian adult patients with epilepsy, lower mean QOLIE-31 scores were obtained compared with previously published international data for overall HRQOL, emotional well-being, and cognitive functioning and social functioning subscales (p < 0.001). Univariate analysis revealed that duration of epilepsy negatively correlated with all QOLIE-31 subscores (p < 0.05), except for emotional well-being (p = 0.1). In multivariate regression analysis, BDI depression score was the predictor of overall score and all QOLIE-31 domains, except for emotional well-being. Age could be considered as a predictor of cognitive and social functioning, medical effects, and the total QOLIE -31 score. Seizure frequency was a factor associated with all HRQOL domains, except for medication effects and emotional well-being, whereas gender, education, family status, seizure type, employment, lateralization of epileptic foci, number of antiepileptic drugs, and the reported adverse events did not significantly affect HRQOL.ConclusionThe present study has revealed that longer duration of epilepsy, older age, higher seizure frequency, and depression are the potential predictors of worse HRQOL in adult Russian patients with epilepsy.     

Predictors of quality of life and their interrelations in Korean people with epilepsy: A MEPSY study

PurposePeople with epilepsy (PWE) are more likely to have impaired quality of life (QOL) than the general population. We studied predictors of QOL and their interrelations in Korean PWE.MethodsSubjects who consecutively visited outpatient clinics in four tertiary hospitals and one secondary care hospital were enrolled. These subjects completed the Korean version of the Neurological Disorders Depression Inventory for Epilepsy (K-NDDI-E), the Generalized Anxiety Disorder-7 (GAD-7), the Quality of Life in Epilepsy-10 (QOLIE-10), and the Korean version of Liverpool Adverse Event Profile (K-LAEP). We evaluated the predictors of QOL by multiple regression analyses and verified the interrelations between the variables using a structural equation model.ResultsA total of 702 PWE were eligible for the study. The strongest predictor of the overall QOLIE-10 score was the K-LAEP score (β = −0.375, p < 0.001), followed by the K-NDDI-E score (β = −0.316, p < 0.001), seizure control (β = −0.152, p < 0.001), household income (β = −0.375, p < 0.001), and GAD-7 score (β = −0.119, p = 0.005). These variables explained 68.7% of the variance in the overall QOLIE-31 score. Depression and seizure control had a bidirectional relationship and exerted direct effects on QOL. These factors also exerted indirect effects on QOL by provoking adverse effects of AEDs. Anxiety did not have a direct effect on QOL; it had only indirect effect through the adverse effects of AEDs.ConclusionDepression, anxiety, seizure control, and adverse effects of AEDs have complex interrelations that determine the QOL of PWE.     

The impact of side effects on long-term retention in three new antiepileptic drugs

ObjectiveTo determine long-term retention, percentage of patients withdrawing because of adverse events, percentage of patients achieving seizure freedom, safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and topiramate.MethodsAll patients treated with lamotrigine, levetiracetam or topiramate in the Epilepsy Centre were identified. Each drug was analyzed from introduction of the drug in the Netherlands up to a final assessment point 2 years later.ResultsData from 1066 patients were included: 336 for lamotrigine, 301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2% (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at p < 0.001; LTG vs. TPM at p < 0.001; LEV vs. TPM at p = 0.005). Seizure freedom rates were lowest for lamotrigine and highest for levetiracetam. Adverse events played a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336 patients (15.5%) on lamotrigine (p < 0.001), 68/301 patients (22.5%) on levetiracetam (p < 0.001). Mood and general CNS-effects are common in patients on lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent in patients on topiramate. A positive effect on cognition is frequently noted in patients on lamotrigine.ConclusionA drug that is only modestly efficacious but has a favourable safety profile may look better than a drug that is more efficacious but produces clinically meaningful adverse events. Therefore, a drug's retention rate is mainly determined by its side effect profile. As a consequence, retention rate was highest for lamotrigine and lowest for topiramate. Intermediate retention rates were seen with levetiracetam use.     

A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy

This study explored the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in patients with pharmacoresistant epilepsy. A total of 60 patients were randomly divided into two groups based on the stimulation zone: the Ramsay-Hunt zone (treatment group) and the earlobe (control group). Before and after the 12-month treatment period, all patients completed the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Liverpool Seizure Severity Scale (LSSS), and the Quality of Life in Epilepsy Inventory (QOLIE-31). Seizure frequency was determined according to the patient's seizure diary. During our study, the antiepileptic drugs were maintained at a constant level in all subjects. After 12 months, the monthly seizure frequency was lower in the treatment group than in the control group (8.0 to 4.0; P = 0.003). This reduction in seizure frequency was correlated with seizure frequency at baseline and duration of epilepsy (both P > 0.05). Additionally, all patients showed improved SAS, SDS, LSSS, and QOLIE-31 scores that were not correlated with a reduction in seizure frequency. The side effects in the treatment group were dizziness (1 case) and daytime drowsiness (3 cases), which could be relieved by reducing the stimulation intensity. In the control group, compared with baseline, there were no significant changes in seizure frequency (P = 0.397), SAS, SDS, LESS, or QOLIE-31. There were also no complications in this group.     

Medication prescribing and patient-reported outcome measures in people with epilepsy in Bhutan

ObjectiveThe aim of this study was to assess medication prescribing and patient-reported outcomes among people with epilepsy (PWE) in Bhutan and introduce criteria for evaluating unmet epilepsy care needs, particularly in resource-limited settings.MethodsPeople with epilepsy in Bhutan (National Referral Hospital, 2014–2015) completed a questionnaire, the Quality of Life in Epilepsy Inventory (QOLIE-31), and an electroencephalogram (EEG). Management gap was the proportion of participants meeting any of six prespecified criteria based on best practices and the National Institute for Health and Care Excellence (NICE) guidelines.ResultsAmong 253 participants (53% female, median: 24 years), 93% (n = 235) were treated with antiepileptic drugs (AEDs). Seventy-two percent (n = 183) had active epilepsy (≥ 1 seizure in the prior year). At least one criterion was met by 55% (n = 138) of participants, whereas the treatment gap encompassed only 5% (n = 13). The criteria were the following: 1. Among 18 participants taking no AED, 72% (n = 13) had active epilepsy. 2. Among 26 adults on subtherapeutic monotherapy, 46% (n = 12) had active epilepsy. 3. Among 48 participants reporting staring spells, 56% (n = 27) were treated with carbamazepine or phenytoin. 4. Among 101 female participants aged 14–40 years, 23% (n = 23) were treated with sodium valproate. 5. Among 67 participants reporting seizure-related injuries, 87% (n = 58) had active epilepsy. 6. Among 111 participants with a QOLIE-31 score below 50/100, 77% (n = 86) had active epilepsy. Years since first AED treatment (odds ratio: 1.07, 95% CI: 1.03, 1.12) and epileptiform discharges on EEG (odds ratio: 1.95, 95% CI: 1.15, 3.29) were significantly associated with more criteria met.ConclusionsBy defining the management gap, subpopulations at greatest need for targeted interventions may be prioritized, including those already taking AEDs.     

Effects of seizure severity and seizure freedom on the health-related quality of life of an African population of people with epilepsy

PurposeThis study aimed at determining the effects of seizure severity and seizure freedom on health-related quality of life (HRQOL) of people with epilepsy (PWE) in the presence of perceived stigma in a sub-Saharan African culture.MethodsHealth-related quality of life was assessed using QOLIE-31 in 93 consecutive adults (56 males and 37 females) with epilepsy. They were stratified into seizure-free, low–moderate seizure severity, and high seizure severity groups based on the seizure type and the number of seizures in the previous 6 months. Other illness variables and sociodemographic variables were also obtained. A 3-item perceived stigma scale was administered. A modified QOLIE-31 (excluding the epilepsy-specific items) was given to 102 age- and sex-matched healthy controls.ResultsThere was moderate negative correlation between seizure severity and mean total HRQOL score as well as scores on the Seizure Worry (p = .000), Overall Quality of Life (p = .000), and Social Function (p = .001) subscales of QOLIE-31. Overall, the healthy control subjects had a higher mean HRQOL score compared with the PWE put together (71.0 + 11.1 vs 64.2 ± 13.6, p = .001). However, there was no difference in the mean HRQOL score between the seizure-free individuals and the healthy controls (p = .270). Seizure severity was associated with HRQOL independent of perceived stigma on a multiple regression analysis.ConclusionThis study provides evidence that seizure severity relates to health-related quality of life in an inverse, graded manner and independent of perceived stigma. Seizure-free people with epilepsy can have quality of life comparable with healthy individuals.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

ObjectiveTo assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.MethodOpen lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.ResultsOne hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.ConclusionIn a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Clinical and demographic characteristics predicting QOL in patients with epilepsy in the Czech Republic: How this can influence practice

ObjectiveThe aim of our study was to assess the influence of different clinical and demographic variables on quality of life (QOL) in patients with epilepsy in the Czech Republic.MethodsOutpatients with epilepsy (n = 268) who visited two neurology departments between 2005 and 2006 were included. Clinical and demographic characteristics were retrieved from medical records. Quality of life was measured by the Quality of Life in Epilepsy Inventory (QOLIE-31). Using multiple regression analysis, we determined which variables were associated with QOLIE-31 overall and subscale scores.ResultsSeizure frequency, employability and psychiatric comorbidity were found to be risk factors for QOLIE-31 overall score, accounting for 33% of the variance in the regression model. Seizure frequency was strong predictor for all seven subscales. Employability explained 10% of the variance in the QOLIE overall score and was the strongest predictor for Overall QOL, Emotional Well-being, Energy/Fatigue and Cognitive Function. Gender, type of seizures, age at onset of seizures, and systemic comorbidity had no significant association in this study.ConclusionsThe present study confirms that besides seizure frequency, employability and comorbid psychiatric conditions are strong predictors of QOL in patients with epilepsy. Interventions focusing on psychosocial problems and identification of factors that hamper employment in patients with epilepsy are necessary for improving QOL in these patients.     

Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate

BackgroundSubjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N = 842) using the validated Quality of Life in Epilepsy Inventory-31 (QOLIE-31).MethodsQOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (≥ 50% and ≥ 75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs).ResultsMean changes were greater among responders for TS (5.2 versus 1.4 for ≥ 50% SFR; 7.5 versus 1.9 for ≥ 75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for ≥ 50% SFR; 56.9% versus 35.8% for ≥ 75% SFR) and all subscales. Responders had significantly higher final scores for TS (LSM difference = 4.0 for ≥ 50% SFR; LSM difference = 5.7 for ≥ 75% SFR) and all subscales except emotional well-being at ≥ 50% SFR. LSM differences exceeded MCIDs at ≥ 75% SFR for TS and five of seven subscales, and two subscales at ≥ 50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall.SignificanceIn clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL.     

Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures

ObjectiveThe aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of ≤ 400-mg/day USL255, Qudexy® XR (topiramate) extended-release capsules, as adjunctive therapy for partial-onset seizures (POS) in adults.MethodsPatients who completed the 11-week double-blind treatment phase of the phase 3 PREVAIL study were eligible to enroll in this 1-year open-label extension (OLE) study (PREVAIL OLE). The primary objective was to evaluate the safety and tolerability of USL255 (including treatment-emergent adverse events [TEAEs]). The secondary objective was to assess seizure frequency in patients (e.g., median percent reduction from baseline in weekly POS frequency, responder rate [proportion of patients with ≥ 25%, ≥ 50%, ≥ 75%, or 100% reduction from baseline in POS frequency], and seizure-free intervals [proportion of patients who were seizure-free for 4, 12, 24, 36, or 48 weeks]). Exploratory clinical-status endpoints included the Global Impression of Change (CGI-C) and Quality of Life in Epilepsy—Problems (QOLIE-31-P) questionnaires. Post hoc analyses evaluated neurocognitive TEAE incidences during the first 11 and entire 55 weeks of treatment and efficacy by patient age and drug-resistant status.ResultsOf the 217 patients who completed PREVAIL (USL255, n = 103; placebo, n = 114), 210 (97%) enrolled in PREVAIL OLE and were included in the ITT population. Across the entire 55-week treatment period, USL255 was generally safe and well tolerated, with low individual neurocognitive TEAE incidences. Seizure reduction was sustained across the year-long study and observed in patient subgroups, including those with highly drug-resistant seizures and those ≥ 50 years of age. Improvements in CGI-C and QOLIE-31-P were also observed.SignificanceThe results of PREVAIL OLE are consistent with those from PREVAIL and demonstrate that adjunctive treatment with up to 400 mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.     

Is antiepileptic drug withdrawal status related to quality of life in seizure-free adult patients with epilepsy?

PurposeThis study aimed to determine factors that influence the quality of life (QOL) of seizure-free adult patients with epilepsy in western China and address whether these determinants vary by antiepileptic drug (AED) withdrawal.MethodsA cross-sectional study was conducted in the epilepsy outpatient clinic of West China Hospital, Sichuan University. Patients with epilepsy who were aged at least 18 years and seizure-free for at least 12 months were interviewed using the Quality of Life in Epilepsy Inventory-31 (QOLIE-31); the National Hospital Seizure Severity Scale (NHS3); the Liverpool Adverse Events Profile (LAEP); the Social Support Rating Scale (SSRS); the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) Questionnaire; and the Scale of Knowledge and Attitudes Toward Epilepsy. Eligible patients were divided into two groups: the nonwithdrawal group and the withdrawal group. The independent-samples t-test was used to compare the QOL between the groups, and linear regression analysis was used to explain the variance of their QOL.ResultsOne hundred and eighty-seven (135 nonwithdrawal and 52 withdrawal) patients were included in the analysis. The QOLIE-31 overall score of the nonwithdrawal group was lower than that of the withdrawal group (p < 0.01). The LAEP score was the strongest predictor of the QOLIE-31 overall score of all subjects, explaining 26.9% of the variance. The second strongest predictor was the SSRS score, explaining 12.9%, and the other predictors were the NHS3 score (5.2%), education level (2.3%), age (1.5%), and marriage (1.0%). Furthermore, the strongest predictors in the nonwithdrawal group were the LAEP and SSRS scores, while in the withdrawal group, the strongest predictors were stigma scores and employment.ConclusionAmong the seizure-free adult patients with epilepsy, those with AED withdrawal experienced better QOL than those continuing AED treatment. Furthermore, the determinants of QOL varied by AED withdrawal. Individual strategies to optimize QOL should be developed based on these differences.     

Lamotrigine serum levels: Ceiling effect in people with epilepsy in remission?

BackgroundAntiepileptic drug titration in epilepsy remains mostly empirical. Since in practice seizure remission may be obtained with low doses, we aimed to determine whether patients in remission have lower lamotrigine levels than those with ongoing seizures.MethodsRetrospective comparison of the distribution of lamotrigine levels among unselected patients in remission and with ongoing seizures. Remission was defined as 3 times the longuest interseizure interval and at least one year. Only trough levels were analyzed.ResultsBetween 2009 and 2014, we identified 93 adults, among whom 10 were in remission. Patients in remission had significantly (p = 0.008) lower serum levels (median 2.3 mg/L, range: 0.7–8.2) than those with ongoing seizures (median 5.4 mg/L, range: 1.1–18.2). We did not find any patient in remission with levels higher than 8.2 mg/L. Distribution of dosages also differed among the groups, but less significantly (median: 175 vs 300 mg, p = 0.03).ConclusionAn association between lamotrigine serum levels and seizure response can be observed. This suggests the existence of a ceiling level, above which remission is unlikely and should prompt antiepileptic medication switch rather than further up-titration of lamotrigine in drug-naïve patients with epilepsy.     

High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high

Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy accounting for 3–12% of adult cases of epilepsy. Valproate has proven to be the first-choice drug in JME for controlling the most common seizure types: myoclonic, absence, and generalized tonic–clonic (GTC). In this retrospective study, we analyzed seizure outcome in patients with JME using valproate monotherapy for a minimum period of one year. Low valproate dose was considered to be 1000 mg/day or lower, while serum levels were considered to be low if they were at or below 50 mcg/dl. One hundred three patients met the inclusion criteria. Fifty-six patients (54.4%) were female. The current average age was 28.4 ± 7.4 years, while the age of epilepsy onset was 13.6 ± 2.9 years. Most patients corresponded to the subsyndrome of classic JME. Forty-six (44.7%) patients were free from all seizure types, and 76 (73.7%) patients were free from GTC seizures. No significant difference was found in seizure freedom among patients using a low dose of valproate versus a high dose (p = 0.535) or among patients with low blood levels versus high blood levels (p = 0.69). In patients with JME, it seems appropriate to use low doses of valproate (500 mg to 1000 mg) for initial treatment and then to determine if freedom from seizures was attained.     

A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine,lamotrigine, or valproate monotherapy

ObjectiveTo investigate the differential effects of fetal exposure to antiepileptic drugs (AEDs) on cognitive fluency and flexibility in a prospective sample of children.MethodsThis substudy of the Neurodevelopmental Effects of Antiepileptic Drugs investigation enrolled pregnant women with epilepsy on AED monotherapy (carbamazepine, lamotrigine, and valproate). Blinded to drug exposure, 54 children were tested for ability to generate ideas in terms of quantity (fluency/flexibility) and quality (originality). Forty-two children met inclusion criteria (mean age = 4.2 years, SD = 0.5) for statistical analyses of drug exposure group differences.ResultsFluency was lower in the valproate group (mean = 76.3, SD = 7.53) versus the lamotrigine (mean = 93.76, SD = 13.5, ANOVA P < 0.0015) and carbamazepine (mean = 95.5, SD = 18.1, ANOVA P < 0.003) groups. Originality was lower in the valproate group (mean = 84.2, SD = 3.23) versus the lamotrigine (mean = 103.1, SD = 14.8, ANOVA P < 0.002) and carbamazepine (mean = 99.4, SD = 17.1, ANOVA P < 0.01) groups. These results were not explained by factors other than AED exposure.ConclusionChildren prenatally exposed to valproate demonstrate impaired fluency and originality compared with children exposed to lamotrigine and carbamazepine.     

Determinants of quality of life in people with epilepsy in Serbia

PurposeThis study aimed at finding determinants of quality of life in people with epilepsy (PWE) living in Belgrade, Serbia.MethodIn this study, we recruited consecutive adults with epilepsy attending our outpatient department. Adult patients (age range: 18–65 years) of normal intelligence and without any progressive neurological disease or psychiatric disorder were included in the study. They completed the following questionnaires: QOLIE-31 Inventory (Serbian version), Beck's Depression Inventory-II, Beck's Anxiety Inventory, Symptom Check List-90, and Neurotoxicity Scale-II. Hierarchical multiple regression analysis was performed to assess the predictive effects of some factors on QOLIE-31 Inventory.ResultsThe mean QOLIE-31 score of 203 patients who completed the questionnaires was 70.64 ± 17.74. Sociodemographic factors (age, sex, education, and employment) did not significantly predict QOLIE-31 score. Significant determinants of quality of life were clinical characteristics – seizure severity and etiology of epilepsy – accounting for 30.9% of the variance, depressive and anxiety symptoms accounting for 42.8% of the variance, and cognitive effects of antiepileptic drugs, accounting for 1.5% above other variables.ConclusionsThe results suggest that seizure severity and etiology of epilepsy, depressive and anxiety symptoms, and cognitive adverse medication effects are main determinants of quality of life in this population of PWE.