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The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up. • Retention rate is more and more recommended as an outcome measure for assessment of efficacy of anti-seizure medication. • By using retention rate and battery replacement rate, long-term efficacy of VNS can be assessed. • A dichotomous approach confirmed the use of retention rate as a reliable surrogate for seizure reduction. • Estimated retention rates of VNS therapy after 15- and 20-years follow-up, were 45% and 33% respectively. • VNS is a well-tolerated therapy, but retention rates decline with long follow-up. [ABSTRACT FROM AUTHOR]

Background Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory epilepsy. Methods This retrospective observational study included TDM-data from the main laboratories and population data from the Norwegian Prescription Database in Norway, in addition to clinical data from medical records of adult patients using ESL for up to three years, whenever possible. Results TDM-data from 168 patients were utilized for assessment of pharmacokinetic variability, consisting of 71% of the total number of patients in Norway using ESL, 2011-14. Median daily dose of ESL was 800 mg (range 400–1600 mg), and median serum concentration of ESL was 53 μmol/L (range 13–132 μmol/L). Inter-patient variability of ESL was extensive, with 25-fold variability in concentration/dose ratios. Additional clinical data were available from 104 adult patients out of the 168, all with drug resistant focal epilepsy. After 1, 2 and 3 years follow-up, the retention rate of ESL was 83%, 72% and 64%, respectively. ESL was generally well tolerated as add-on treatment, but sedation, cognitive impairment and hyponatremia were reported. Hyponatremia (sodium <137 mmol/L) was present in 36% of the patients, and lead to discontinuation in three. Conclusion Pharmacokinetic variability of ESL was extensive and the demonstration of usefulness of TDM requires further studies. In patients with drug resistant focal Epilepsy, the high retention rate indicated good efficacy and tolerability. Hyponatremia was observed in one third of the patients. The present results point to a need for individualization of treatment and TDM may be useful. [ABSTRACT FROM AUTHOR]

Summary Objective To evaluate the effectiveness of rufinamide (RFM) in patients with Lennox–Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes using time to treatment failure (retention rate) as the outcome measure. Methods In this retrospective cohort study, characteristics and outcomes of all patients receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM failure, defined as discontinuation of RFM or initiation of an additional antiepileptic therapy. The secondary outcome measure was discontinuation of RFM. Kaplan–Meier method survival curves were generated for time to RFM failure, for all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The impact of age, seizure type, fast or slow drug titration, and concomitant therapy with valproate on retention rate were evaluated using Cox regression models. Results One hundred thirty-three patients were included, 39 (30%) of whom had LGS. For all patients, the probability of remaining on RFM without additional therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31–0.83), with a median time to failure of 18 months in LGS compared to 6 months in all others ( p = 0.006). Conclusions In a broad population of children with refractory epilepsy, around half will continue taking the medication for at least a year without additional therapy. Patients with LGS are two times more likely to continue RFM without additional therapy compared to those without LGS. [ABSTRACT FROM AUTHOR]

Purpose Eslicarbazepine acetate (ESL) is a new generation voltage-gated sodium channel blocker. It has completed one phase II clinical trial and three phase III clinical trials, two of which with 1-year open label extensions. ESL was approved in 2009 by the European Medicines Agency as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. It is marketed in Portugal since April 1st 2010. Despite good safety and efficacy shown in clinical trials, little is known about its effectiveness in a clinical day-to-day setting. Our purpose was to assess the post-marketing experience with ESL in our centre, in terms of safety and efficacy profile, and ascertain whether the results were comparable to the published data. Methods This is a retrospective, consecutive, single-centre 2-year observational study. All the patients who initiated treatment with ESL between April 1st 2010 and October 31st 2011 at Hospital de Santo António were consecutively included. Data was collected on demographics, clinical features, adverse events and treatment response, using a standardized data form. Follow-up data was considered until October 31st 2013. Efficacy analysis was performed using an "intention to treat" approach. Key findings We included 152 patients, 74 (48.7%) female. Mean age was 38.5 years-old (sd = 14.2). Eight patients were less than 18 years old. Mean epilepsy duration was 26.8 (sd = 13.1) years and mean seizure frequency in the previous 3 months was 19.7 seizures per month. At baseline, about 57.9% of all patients were taking ≤2 concomitant AEDs. The total adverse rate was 42.1% (64/152), with 50.0% (32/64) leading to treatment discontinuation. The most frequent adverse events were dizziness and somnolence/slowness. Adverse events were higher in regimens including carbamazepine, and mean age was higher in the patients reporting adverse events. Retention rates as estimated by Kaplan-Meyer curves were 82.9%, 71.3%, 65.1% and 62.8%, respectively, at 6, 12, 18 and 24 months. Retention time was not influenced by gender, diagnosis, age or epilepsy duration. Fifty-six patients (36.8%) dropped out of treatment, 32 (57.1%) due to adverse events, 19 (33.9%) due to lack of efficacy and 5 (8.9%) for other reasons. At 6,12,18 and 24 months, the responder rates were 25.7%, 25.7%, 19.0% and 17.1%, respectively and favourable global clinical impression rates were 27.7%, 19.7%, 17.8% and 16.5%. Significance This is the first study reporting follow-up data for up to 2 years in patients treated with ESL in the setting of daily clinical practice. The retention rates in our study are sustained throughout the 2 years of follow-up, and at 6 and 12 months are globally comparable to those of phase III trials and open-label extensions. The adverse event rate is also comparable to previous studies, and no new safety issues attributable to ESL were found. Responder rates were lower than those of previous studies, even though efficacy results must be interpreted with caution given the different study design. Thus, ESL appears to be a clinically useful add-on AED, with good safety profile and high retention rates, even in a very refractory group of patients like the presented cohort. [ABSTRACT FROM AUTHOR]

Summary: This is a large-sample, prospective, long-term observational study to assess the retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy. The retention rate was calculated by Kaplan–Meier method using intention-to-treatment analysis. Cox proportional hazard models were used to analyze the risk factors for retention rate. A total of 229 patients were enrolled into this study. The retention rate was 75.5% at 1 year, 47% at 6 years. Three risk factors for treatment failure were female gender, rural residence, and frequent seizures before treatment. Four predominant causes leading to treatment failure were: lack of efficacy (7.4%), adverse effects (10.9%), follow-up loss (15.7%), and subjective misunderstanding (8.3%). Adverse effects occurred in 129 (56.3%) patients, with 7 (3.1%) patients suffered from renal calculus. This study suggests the long-term retention rate of topiramate as initial monotherapy is high in Chinese patients. Lower initial dose, lower target dose and slower titration contribute to better tolerability. Frequent abdominal ultrasound for detecting renal calculus is necessary. Rural patients and patients with poor education level should be paid more attention by physicians to ensure continued therapy. [Copyright &y& Elsevier]