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Epilepsy management in elderly patients is often complex because of several concomitant comorbidities that may limit the use of some antiepileptic drugs (AEDs). Levetiracetam (LEV) is a second-generation AED widely used in elderly patients with epilepsy while lacosamide (LCM), which has been recently approved in European Union (EU) as monotherapy for the treatment of focal onset seizures, is affected by a scarcity of data in such frail population. This study is aimed at assessing the efficacy and the tolerability of LCM as monotherapy in elderly patients affected by focal onset epilepsy compared with those receiving LEV. A retrospective chart review of patients aged ≥ 65 years suffering from focal onset seizures, with or without secondary generalization on LCM monotherapy or LEV monotherapy, was performed. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, number of lifetime AEDs, seizure frequency at baseline and at 12 months of follow-up, and seizure freedom rates were reported. In this observational retrospective study, 22 patients on LCM (10 males, 12 females, mean age: 76.23 ± 7.5) and 24 patients on LEV (10 males, 14 females, mean age: 73.58 ± 6.39) were enrolled. Mean LCM daily dose was 204.51 ± 88.51 mg and mean LEV daily dose was 1281.25 ± 378.15 mg. All patients had comorbidities on chronic treatment. At 12 months of follow-up, mean monthly seizure frequency reduced from 4.23 ± 8.53 to 0.33 ± 0.9 (p <.001) in LCM group and from 2.29 ± 6.11 to 0.2 ± 0.81 (p <.001) in LEV group. Furthermore, 16/22 (72.7%) LCM patients were seizure-free at 12 months of follow-up while seizure freedom was achieved by 17/24 (70.8%) patients in LEV group. Epilepsy management in elderly patients is often challenging. In this retrospective real-life study, the efficacy and the tolerability of LCM as monotherapy was favorable even at low doses in older patients and comparable with LEV with a high rate of long-term seizure freedom. Considering the frequent comorbidities and the risk of drug–drug interactions, LCM monotherapy may be a valuable option in elderly patients with focal onset epilepsy because of its favorable pharmacokinetic profile. [ABSTRACT FROM AUTHOR]

Abstract Purpose While antiepileptic drug (AED) treatment effectiveness is traditionally assessed based on seizure frequency reduction (SFR), the overall value of AEDs in managing epilepsy and associated sequelae may be best assessed by how patients feel and function in terms of overall health-related quality of life (HRQoL). We conducted a pooled analysis of the Quality of Life in Epilepsy-31 (QOLIE-31) questionnaire from two phase 3 trials to explore the effect of response to conversion to eslicarbazepine acetate (ESL) monotherapy on HRQoL. Methods Data were pooled from two multicenter, randomized, double-blind, historical control phase 3 trials examining conversion to ESL monotherapy in adults with inadequately controlled partial-onset seizures (POS). The relationship between HRQoL and ESL treatment response was examined through the analysis of week 18 QOLIE-31 scores between patients who met the SFR ≥ 50% threshold (responders) and patients with SFR < 50% (nonresponders). The analysis was conducted in the efficacy population (intent-to-treat (ITT) patients who entered the AED taper/conversion period) and completer population (efficacy patients who completed the ESL monotherapy period) and was repeated using an SFR ≥ 75% threshold. Results In the efficacy population, week 18 QOLIE-31 total score least squares mean (LSM) was significantly higher for responders with ≥ 50% SFR (LSM difference: 3.0; 95% confidence interval (CI): 0.2–5.8; p = 0.037) and with ≥ 75% SFR (LSM difference: 7.0; 95% CI: 3.6–10.3; p < 0.001) than nonresponders. In the completer population, overall quality of life (QoL) (LSM difference: 5.1; 95% CI: 1.5–8.6; p = 0.006) and social functioning (LSM difference: 5.4; 95% CI: 0.1–10.7; p = 0.046) were significantly higher for responders with ≥ 50% SFR than nonresponders, and all domain LSMs were higher for responders with ≥ 75% SFR (all p < 0.05) than nonresponders. Conclusions This analysis of data from the phase 3 trials demonstrated significantly higher HRQoL among ESL responders with SFR of ≥ 75% and also at the lower SFR threshold of ≥ 50% compared with nonresponders. Highlights • HRQoL improved as seizure frequency was reduced from > 50% to > 75% below baseline. • Responders achieved a 3- to 7-point difference in QOLIE-31 total score above nonresponders. • The Completer populations had significant improvements in all seven domain scores. [ABSTRACT FROM AUTHOR]

• The first study about PER and LCM monotherapy in pediatric patients with focal epilepsy. • Evaluating efficacy, tolerability of PER and LCM monotherapy in pediatric patients. • Evaluating the impact on emotion and behavior of PER and LCM monotherapy in pediatric patients. Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy. This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4–16) at baseline and after three and six months. Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy. The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China. [ABSTRACT FROM AUTHOR]

• Perampanel can be used as initial monotherapy and as add-on therapy. • The effect of converting to perampanel monotherapy from add-on therapy is unknown. • This was a non-interventional study in Korean patients with focal-onset seizures. • Conversion to perampanel monotherapy from adjunctive therapy was effective. • Perampanel was well tolerated and no new safety signals were identified. To assess the effectiveness and tolerability of perampanel monotherapy following conversion from adjunctive therapy. This was a multicenter, retrospective, non-interventional study of Korean patients aged ≥12 years with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures. Data were extracted from electronic medical records of perampanel-treated patients from 1 February 2016 to 31 October 2020. Kaplan–Meier estimated retention rates, effectiveness, and safety were recorded. Subjects (n = 66, mean age 46.2 years) were mostly male (68.2%) with focal to bilateral tonic-clonic seizure (71.2%). Mean duration of illness was 86.3 months. Retention rates after conversion to perampanel monotherapy at 3, 6, and 12 months (primary outcome) were 96.0%, 96.0%, and 75.6%, respectively. Overall retention rates in patients receiving perampanel as adjunctive or monotherapy at 3, 6, 12, 18, and 24 months after perampanel add-on were 100%, 98.3%, 95.9%, 92.6%, and 92.6%, respectively. Mean retention duration was 41.2 months (overall perampanel administration) and 21.4 months (monotherapy). Mean seizure frequency/28 days in the Full Analysis Set (n = 61) was comparable for adjunctive and monotherapy (0.2 ± 0.79 vs 0.2 ± 0.64; change between adjunctive and monotherapy periods: 0.0 ± 0.59; p = 0.498). Perampanel was well tolerated and no new safety signals were identified. Dizziness (4.6%), only reported during adjunctive therapy, was the most common treatment-emergent adverse event. Conversion to perampanel monotherapy from adjunctive therapy showed promising results in subjects with FOS with/without focal to bilateral tonic-clonic seizures; further studies in a larger population are needed to confirm these encouraging data. [ABSTRACT FROM AUTHOR]

• Perampanel is approved for use as monotherapy in approximately 48 countries. • This review examines the use of perampanel monotherapy in patients with epilepsy. • Perampanel monotherapy use offered favorable seizure freedom and retention rates. Perampanel, a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, is a once-daily oral anti-seizure medication (ASM) for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCS). In the US, perampanel is approved for the treatment of FOS (adjunctive and monotherapy), with or without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥4 years, and as adjunctive treatment of GTCS in patients aged ≥12 years. The monotherapy approvals in the US were based on the Food and Drug Administration's (FDA's) policy allowing extrapolation of adjunctive data to the monotherapy setting in the absence of randomized controlled monotherapy trials; since then, perampanel monotherapy has received approvals in approximately 48 countries. As there are key differences in clinical evidence of perampanel as adjunctive therapy vs monotherapy, we review the clinical outcomes of perampanel when administered as primary or secondary monotherapy. Eight publications reporting the efficacy and safety outcomes of perampanel monotherapy in clinical trial and real-world settings were selected during our literature search and are included; these comprise three Eisai-sponsored studies in patients with epilepsy: one prospective, open-label, Phase III clinical trial of patients with newly diagnosed epilepsy (Study 342 [FREEDOM]) and two retrospective, real-world Phase IV studies of patients with epilepsy who received perampanel during routine clinical care (Studies 504 and 506 [PROVE]); and five retrospective, real-world studies in patients with epilepsy who were prescribed perampanel during routine clinical care. Results from these studies demonstrated that seizure freedom may be achieved following treatment with perampanel monotherapy (either primary or secondary), with favorable retention rates and safety profiles. Overall, the clinical evidence supports the use of perampanel monotherapy both in newly diagnosed patients and in those who have been unable to control their seizures with other ASMs. [ABSTRACT FROM AUTHOR]

Abstract: We sought to understand the issues that lead from the need to change antiepileptic drugs (AEDs) and how this may influence someone's feelings regarding swapping to another drug. We conducted semistructured interviews with 14 people with epilepsy, four months after changing from AED monotherapy. Interviews were digitally recorded, transcripts were coded independently, and thematic analysis was undertaken through group work. There were seven major themes: failure, the reason behind the failure, and the experience itself; expectations; previous experience; personality and life events; side effects; impact of diagnosis; and outcome. Clinical outcome and patients' ideas of outcome were often discordant. Each drug change arises from a position of failure that elicits strong feelings of loss of control and vulnerability in participants. Recognizing the need for counseling of targeted individuals undergoing AED change is key. Unresolved emotional issues surrounding biographical disruption following diagnosis were potent modifiers of the change process. [Copyright &y& Elsevier]

• Drug titration is an essential component in the treatment of patients with epilepsy. • Start low, go slow initiation of many antiseizure medications (ASMs) is recommended. • Transitional or chronic polytherapy increases the potential for adverse effects. • Flexible titration and adjustment of concomitant ASMs may improve tolerability. • Communication with patients during titration may help promote adherence. The variable response to antiseizure medication (ASM) treatment and the numerous drug- and patient-related factors that must be considered when initiating therapy make drug titration to an optimal and tolerable dose an essential component in the pharmacologic treatment of patients with epilepsy. When initiating a new ASM, a "start low, go slow" titration approach is generally recommended and has been shown to reduce the risk of severe idiosyncratic reactions with certain medications and improve tolerability with regard to many frequently occurring central nervous system-related adverse effects (e.g., somnolence, dizziness). Many patients with epilepsy will require medication changes due to lack of efficacy or intolerability of the initial regimen. When this occurs, patients may be switched from one monotherapy to another or receive adjunctive therapy. When transitioning a patient from one ASM to another (referred to as monotherapy conversion or transitional polytherapy), there are several strategies for tapering the baseline ASM depending on the clinical scenario. Regardless of the particular strategy, the goal should be to discontinue the baseline ASM in order to prevent increased toxicity due to drug load. When adding on ASM therapy, flexible titration of the new ASM and adjustment of concomitant ASMs to achieve disease control with the lowest possible drug load (lowest numbers and lowest doses) may help improve tolerability of the add-on therapy. Communication with patients during the initiation of a new therapy may help patients adhere to the titration schedule, allowing them to reach their optimal maintenance dose. [ABSTRACT FROM AUTHOR]

Abstract: A prospective multicenter observational study was undertaken on children and adults with epilepsy in whom first monotherapy failed, to assess indications and effects of alternative monotherapy vs. polytherapy. Patients were followed until 12-month remission, drug withdrawal, or up to 18months. Monotherapy and polytherapy were compared for patients' baseline features, indication, retention time, remission, adverse events (AE), quality of life, and direct and indirect costs. Included were 157 men and 174 women, aged 2–86years. Of the patients, 72.2% were switched to alternative monotherapy. Baseline treatment was changed for lack of efficacy (73.9%) or adverse events (26.1%). Two hundred forty-three completed the study (remission: 175; 72.0%). Retention time, hospital admissions, days off-work and off-school, and quality of life did not differ between the two treatment groups. Patients were followed for 365.3person-years. Three hundred eighty-three incident AEs were reported by 46.4% of patients in monotherapy and 40.2% in polytherapy (serious AEs: 9.6% vs. 8.7%, mostly nondrug-related). [Copyright &y& Elsevier]

Abstract: Purpose: To determine whether antiepileptic drug (AED) characteristics are associated with medication adherence. Methods: We reviewed pharmacy and clinical records of 108 patients with epilepsy from the indigent care program at Shands-Jacksonville. We calculated the mean medication possession ratio (MMPR) for each AED. Using univariate analysis, we determined whether differences exist in the MMPR of various AEDs. We also determined whether the MMPR differs accordingly to the use of mono- or combination therapy, dosing frequency, release-type, or brand-name formulation. We employed multivariable analysis to determine if these differences persisted in the context of other demographic and clinical variables. Results: Mean medication possession ratio was higher (better) when using older AEDs, in monotherapy, and with more frequent dosing intervals. These variables remained significant on multivariable analysis. Conclusion: Our findings contradict some commonly held beliefs on medication adherence and suggest that specific AED characteristics may be superseded by factors such as overall patient satisfaction with the drug regimen. [Copyright &y& Elsevier]

Abstract: The quality of life (QOL) of individuals with well-controlled epilepsy (WCE) is often not considered. We therefore investigated predictors determining QOL in patients who had been seizure free at least 1year on stable antiepileptic drug (AED) monotherapy. They were asked to complete self-report health questionnaires, including the Beck Depression Inventory (BDI), Adverse Event Profile (AEP), and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We looked for predictors of QOLIE-31 scores among the various demographic, socioeconomic, and clinical factors and BDI, and AEP scores. Depression symptoms were manifested by 18.7% of patients. People with depression symptoms were more likely to report adverse events than those without depression symptoms. The strongest predictor of QOL was BDI score, followed by AEP total score, years of education, and income. BDI score had 3.37 times the effect of AEP total score. In conclusion, QOL of patients with WCE is determined mainly by depressive symptoms. [Copyright &y& Elsevier]

Abstract: “Classic” and “newer” antiepileptic drugs (AEDs) were compared in an epidemiological survey regarding patient''s acceptance of AEDs, quality of life (QoL), and employment. Data from 907 outpatients, 45.9% female (mean age: 44.8±17.9years), were evaluated by 90 neurologists in private practices, who were also involved in a non-interventional study by Sanofi–Aventis Deutschland GmbH, regarding medication, seizure type, illness duration, employment, patients’ acceptance of AEDs (4-point scale where 1=very good), and QoL (6-point scale where 1=very good). Among the patients, 69.7% were on monotherapy, 25.4% were taking two AEDs, and 4.9% were taking more than two AEDs. Patient''s acceptance of AEDs (mean±SD=1.65±0.62) and QoL (2.34±0.89) were “good.” Among patients aged 18–65years, 68.6% were employed. QoL and acceptance were lower with polytherapy. Older age and polytherapy were associated with lower probability of employment. No differences emerged between “classic” and “newer” AED monotherapy. Polytherapy-associated lower QoL could be due to severity of illness or adverse effects of treatment. [Copyright &y& Elsevier]

Abstract: This open-label, non-interventional, controlled surveillance study evaluated the cognitive outcome of patients administered levetiracetam (LEV) or carbamazepine (CBZ) monotherapy as primary treatment or as substitution for previous treatment. Executive functions, verbal memory, and subjective ratings were assessed before and 6months after initiation of LEV or CBZ monotherapy. Analyses included 498 patients: 370 received LEV (63% pretreated), and 128 CBZ (34% pretreated). Mostly because of the substitution condition, the seizure freedom rate was slightly higher with LEV as opposed to CBZ (78% vs 69%). Almost all cognitive measures improved with LEV but not with CBZ, and repeated-measures MANOVA did not indicate seizure control or pretreatment as decisive with respect to cognitive change. With LEV, executive functions improved in 15% and deteriorated in 5% of patients; the opposite pattern was seen under CBZ (improvement with LEV OR=2.3, deterioration with CBZ OR=3.4). The findings suggest a mild but definitely superior cognitive outcome with LEV as opposed to CBZ monotherapy. [Copyright &y& Elsevier]

Abstract: This 24-week, multicenter, open-label trial was designed to evaluate the dosing, effectiveness, and safety of topiramate monotherapy for epilepsy and to identify patient and clinical characteristics predictive of optimally effective stabilized monotherapy doses. Of 406 randomized patients, 244 comprised the evaluable-for-efficacy population (⩾12weeks of treatment and stabilized topiramate dose during final 28days); 213 were on topiramate monotherapy at the end of the trial. The mean stabilized daily dose of topiramate over the last 28days of treatment (primary endpoint) was significantly lower for patients reporting one to three seizures (low seizure frequency, n =147) than for those reporting more than three seizures (high seizure frequency, n =66) during a 3-month retrospective baseline period (191mg vs 239mg, P =0.003). Patients in the low-seizure-frequency group reached a stable topiramate dose after a median of 36days, compared with 53days for patients in the high-seizure-frequency group. Linear and stepwise regression analyses showed baseline seizure frequency and lifetime seizure count to be significant (P <0.05) predictors of the stabilized dosage. Most treatment-emergent adverse events (TEAEs) were mild to moderate; those occurring with cumulative incidence rates >10% in either seizure frequency group were paresthesia, fatigue, anorexia, dizziness, somnolence, headache, and hypoesthesia; 18.2% of patients discontinued topiramate because of a TEAE, 5.1% reported serious TEAEs, and no deaths were reported during the study. [Copyright &y& Elsevier]

Abstract: Objective: The aim of the study described here was to investigate the efficacy, tolerability, and side effects of oxcarbazepine (OXC) monotherapy in newly diagnosed, previously untreated adult and elderly patients with partial epilepsy. Methods: We prospectively analyzed and recorded the efficacy, tolerability, and side effects of OXC monotherapy. The results were analyzed on the basis of etiologic classifications and age distributions. Remission was defined as seizure freedom for at least 1 year. Results: A total of 147 patients were evaluated in a single center for a median of 18 months (range: 14–36 months). Overall, 92 patients (62.6%) were seizure free for at least 12 months and 55 of them (37.4%) were unresponsive despite treatment with the maximum tolerable dose of OXC. There was a significant difference in the outcomes of patients with cryptogenic (75% remission) and symptomatic (51.9% remission) epilepsy (P =0.004). Patients with cerebral tumors did worse than the remainder of the patients in the symptomatic group (36.7% remission) (P =0.03). Results were favorable for the elderly; 14 patients (73.6%) in the elderly subgroup became seizure free for at least 1 year, and the remission was achieved with low to moderate doses (approximately 900mg/day). Overall, 13 patients (8.8%) discontinued OXC due to intolerable side effects. Side effects leading to discontinuation were: Stevens–Johnson syndrome (n =2, 1.4%); fatigue and drowsiness (n =2, 1.4%); dizziness, nausea, and vomiting with normal laboratory tests (n =2, 1.4%); dizziness, nausea, and vomiting with serum Na levels <130 mEq/L (n =5, 3.4%); and elevated serum γ-glutamyl transferase levels (GGT>200mg/dL) (n =1, 0.7%). OXC proved to be a tolerable drug for the elderly; only one patient experienced symptomatic hyponatremia with mild symptoms and responded well to fluid restriction, which did not lead to discontinuation of OXC. Conclusion: Although the limitations of our study include its open-label design, the results suggest that OXC monotherapy may be regarded as an effective first-line monotherapy option for adult and elderly patients with partial epilepsy, but has low efficacy in patients with cerebral tumors. [Copyright &y& Elsevier]

Abstract: To develop expert consensus for conversion between antiepileptic drug (AED) monotherapies, an 11-member panel used the Delphi Technique over three rounds to: (1) identify relevant issues, (2) vote on the issues, and (3) develop consensus. The panel agreed on the basic principle to taper the existing AED only after a presumably efficacious dose of the planned AED was reached. Application is modified by adverse effects possibly attributable to the existing drug, in which case earlier or more rapid tapering of the existing drug should be considered. Patients with uncontrolled seizures, as well as seizure-free patients for whom driving privileges are a consideration, may benefit from slower tapering by smaller dosage decrements of the existing AED. For 10 of the 12 AEDs considered, the panel made titration recommendations concerning initial and target doses for the planned AED, supplementing limited data in the prescribing information. This expert guidance will aid in the period of transitional polytherapy with AEDs from monotherapy to monotherapy. [Copyright &y& Elsevier]

Abstract: Objective: This prospective, open-label, multicenter study evaluated the efficacy and tolerability of oxcarbazepine as monotherapy in patients with partial seizures who switched from their current antiepileptic drug (AED) monotherapy because of lack of efficacy or poor tolerability. Method: Patients (⩾12 years old) experiencing 2–40 seizures per month while receiving an AED were included. During a 16-week treatment phase, oxcarbazepine was initiated (8–10mg/kg for children; 600mg/day for adults) and titrated up over 4 weeks while the existing AED was tapered off. Improvement in seizure frequency (defined as ⩾50% reduction compared with baseline) was evaluated for all patients, as well as the subgroups of patients switched due to poor tolerability or lack of efficacy. Results: Overall, 52% of patients experienced a ⩾50% reduction in seizure frequency, 35% had a ⩾75% reduction, and 18% were seizure-free. The most frequent (>10%) adverse events were dizziness, nausea, headache, somnolence, and fatigue. Overall, 17% of patients prematurely withdrew because of an adverse event; 62% of these withdrawals occurred during the conversion period. Conclusion: Oxcarbazepine as monotherapy may be a favorable treatment option for patients with partial seizures or poor tolerability of their existing monotherapy regimen. [Copyright &y& Elsevier]

Abstract: The long-term effects of zonisamide as monotherapy or adjunctive therapy were investigated in patients with seizure disorders. One hundred twelve adult neurology patients treated with zonisamide were retrospectively identified through a chart review; 90 patients (n =45 monotherapy, n =45 adjunctive therapy) who received zonisamide for ⩾3 months were included in the efficacy-evaluable population, and all 112 patients were included in the safety population. The average duration of treatment was 24.3 months (range, 3–46 months), and the average zonisamide dosage was 324mg/day (range, 100–1000mg/day). Thirty-eight of 90 patients (42%; n =25 monotherapy, n =13 adjunctive therapy) were seizure-free, and an additional 26 patients (29%; n =9 monotherapy, n =17 adjunctive therapy) had ⩾50% seizure frequency reduction at the last follow-up visit. Thirty of 112 patients (27%) reported mild to moderate adverse events, such as weight loss (5.4%), fatigue (4.5%), and sedation (2.7%). Zonisamide, as monotherapy or adjunctive therapy, was a safe, effective, and well-tolerated long-term treatment option in patients with various seizure types. [Copyright &y& Elsevier]

Abstract: A dosing algorithm was used to guide the conversion of 77 patients with epilepsy (⩾16 years of age) from valproate monotherapy through lamotrigine adjunctive therapy at 200mg daily to lamotrigine monotherapy at 500mg daily in an open-label study comprising a lamotrigine escalation phase (8 weeks), a valproate withdrawal phase (⩽6 weeks), and a lamotrigine monotherapy phase (4 weeks). The algorithm was designed to maintain stable trough concentrations of lamotrigine during valproate withdrawal to minimize seizure risk. Of the 77 patients, 11 prematurely withdrew for administrative reasons (noncompliance, consent withdrawn, loss to follow-up, protocol violation). Of the remaining 66 patients, 18 withdrew because of adverse events, and 48 completed the study. Among the 67 patients with at least one lamotrigine trough serum concentration after initiation of therapy (pharmacokinetic population), mean trough serum concentrations at the end of the lamotrigine escalation phase at a lamotrigine daily dose of 200mg (7.9μg/mL, SD=3.3) did not differ significantly from values during the valproate withdrawal phase (8.7μg/mL, SD=3.5) and the lamotrigine monotherapy phase at a lamotrigine dose of 500mg daily (7.2μg/mL, SD=3.3). A similar pattern of results was observed among the 34 patients who completed the study on lamotrigine (completer population). No serious rashes were reported, and the incidence of withdrawals because of decreased seizure control was low (n=2, or 3%; both incidents were judged to be related to noncompliance). By employment of a four-step dosing algorithm, lamotrigine serum concentrations can be maintained at a stable level with favorable tolerability during a transition from lamotrigine 200mg daily as adjunctive therapy with valproate to lamotrigine monotherapy 500mg daily. [Copyright &y& Elsevier]

Lamotrigine (LTG) was added to other antiepileptic drugs (AEDs) in a study of adjunctive therapy. In addition to seizure control and adverse effects, patients were evaluated for changes in mood states and quality of life. The Profile of Mood States (POMS) and 31-item Quality of Life in Epilepsy (QOLIE-31) instruments were administered at baseline (N=196), after addition of LTG as adjunctive treatment (N=155), and after withdrawal of other drugs to LTG monotherapy (N=51). POMS scores correlated highly with the QOLIE-31 Emotional Well-Being subscale, a known measure of mood. All POMS subscales were significantly improved (all P<0.0001) at the end of the adjunctive therapy phase. POMS scores remained significantly better than baseline among patients completing the conversion to monotherapy (all P<0.003). Minimal clinically important changes were determined for POMS scores. These data indicate that LTG improves mood states to a clinically important degree, even in the presence of other AEDs. The improvement likely was not a synergy but attributable only to LTG because it remained stable after withdrawal of the other AEDs. [Copyright &y& Elsevier]

Oxcarbazepine (OXC, Trileptal) is a modern antiepileptic drug (AED) used as both monotherapy and adjunctive therapy for the treatment of partial seizures with or without secondary generalization in adults and children above 4 years (USA) or 6 years (Europe) of age. Although OXC has been developed through structural variation of carbamazepine (CBZ) with the intent to avoid metabolites causing side effects, significant differences have emerged between the two drugs. The mechanism of action of OXC involves mainly blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its keto moiety to form the monohydroxy derivative (MHD), which is glucuronidated and excreted in the urine. The involvement of the hepatic cytochrome P-450-dependent enzymes in the metabolism of OXC is minimal. Although it does not prevent interaction with oral contraceptives, it explains why OXC can be more effectively combined with other AEDs such as valproate compared with CBZ. Switching from CBZ to OXC normalized CBZ-associated thyroid and sexual hormone abnormalities and pathological lipid values in small patient samples. OXC is often better tolerated than CBZ and causes fewer rashes than CBZ. Add-on or substitution treatment with OXC was effective in controlled trials even when CBZ did not achieve sufficient seizure control. This constitutes compelling clinical evidence that OXC and CBZ are distinctly different medications. From postmarketing experience in over 1,000,000 patient years, OXC had an advantageous risk–benefit balance also in comparison to other new AEDs. OXC should be preferred over CBZ and other older AEDs because of its proven efficacy and excellent side effect profile in children, adolescents, and adults with partial seizures. [Copyright &y& Elsevier]

In a retrospective chart review, we identified 35 patients with medically refractory epilepsy (MRE) who had been converted from polypharmacy to monotherapy and maintained on monotherapy for at least 12 months. None of the 35 patients had worsening of their seizure frequency after the conversion to monotherapy. Fourteen of the 35 patients (40%) became seizure-free. Nine of 35 patients (26%) had a 50% reduction in seizure frequency. Five of 35 patients (14%) had a 75% reduction in seizure frequency. Twenty-eight (80%) of 35 patients participated in a quality-of-life questionnaire. Quality of life was rated as better on monotherapy as compared with polypharmacy in a number of domains: memory loss, concern over medication long-term effects, difficulty in taking the medications, trouble with leisure time activities, and overall state of health. This improvement reached statistical significance. Conversion to monotherapy in patients with MRE may be successful in achieving a reduction in seizure frequency and an improvement in quality-of-life parameters. A prospective, randomized trial is necessary to validate these findings. [Copyright &y& Elsevier]

Objective. This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects.Methods. This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician’s choice). Patients were converted during an &les;8-week Escalation/Taper Phase from their prestudy antiepileptic drug (carbamazepine, phenytoin, or valproate) to lamotrigine via a protocol-specified dosing algorithm or to conventional therapy via standard dosing guidelines. After monotherapy was achieved, patients continued in the study for a 24-week Maintenance Phase.Results. More lamotrigine patients (65%) than conventional therapy patients (57%) completed the 24-week Maintenance Phase (primary efficacy endpoint). The mean time to withdrawal from the study was 175 days (SD=83.1) for lamotrigine patients compared with 156 days (SD=80.7) for conventional therapy patients. Adverse events, the most common reason for discontinuing the Maintenance Phase, accounted for 16% of withdrawals among lamotrigine patients compared with 26% of withdrawals among conventional therapy patients. The mean reduction in seizure frequency was 53% (SD=55.1) for patients using lamotrigine compared with 32% (SD=149.9) for patients using conventional therapy. Humanistic measures including investigator global assessment, the patient self-assessment, and QOLIE-31 scores show that lamotrigine monotherapy was perceived by both physicians and patients to have benefits over monotherapy with conventional antiepileptic drugs.Conclusions. Converting from monotherapy with a less effective or poorly tolerated conventional antiepileptic drug to monotherapy with lamotrigine is associated with better clinical and humanistic outcomes than converting to an alternative conventional antiepileptic drug. [Copyright &y& Elsevier]

To be approved for monotherapy by regulatory authorities, new antiepileptic drugs (AEDs) must first be tested in well-controlled studies in refractory patients (conversion to monotherapy trials) or in patients with newly diagnosed epilepsy. However, the applicability of the information obtained in these trials to day-to-day clinical practice is limited. Clinical trials in newly diagnosed patients, particularly those allowing dose flexibility, offer more useful information, but a close scrutiny of methodological details is required to avoid misinterpretation of the findings. In many instances, the neurologist has a drug with a label, but lacks critical information on optimal titration rates, optimal target and maintenance dosages, response rates in populations with different epilepsy syndromes, different age ranges and comorbidities, and long-term safety data. Such information becomes available only through general clinical experience, well-designed phase IV studies, and postmarketing surveillance. [Copyright &y& Elsevier]

We identified 37 patients with a history of partial seizures, with and without secondarily generalization, who received levetiracetam (LEV) (Keppra) monotherapy. Patients began LEV either as first line therapy (n=9) or were converted to LEV monotherapy (n=28) after failing prior antiepileptic medications (AEDs). Thirty-four patients continued on LEV for at least six months; of these, 13 patients became seizure free and 15 patients had >50% reduction in their seizures. Three patients discontinued LEV because of adverse effects. LEV monotherapy can be effective and well tolerated in adults with new onset and difficult-to-control partial epilepsy. A prospective, large, double blind monotherapy study is needed to confirm this finding. [Copyright &y& Elsevier]

An international trial comparing remacemide hydrochloride with carbamazepine was undertaken in newly diagnosed epilepsy using a novel double-blind, parallel group, double triangular sequential design. Patients with two or more partial or generalized tonic–clonic seizures in the previous year were randomized to 600 mg daily of remacemide or carbamazepine. Subsequent dosage adjustments were allowed while maintaining the blind. The trial completed 20 months after initiation following the second interim analysis. Efficacy data on 449 patients showed carbamazepine to be significantly more effective than remacemide in preventing seizure recurrence (P = 0.003). Median time to first seizure after titration, the primary endpoint, was 112 days for remacemide and 306 days with carbamazepine. Time to second, third, and fourth seizures after randomization all significantly favored carbamazepine. Remacemide was shown unequivocally to be inferior to carbamazepine in this patient population. This study also establishes carbamazepine as a proven treatment for use in subsequent active control comparative trials. [Copyright &y& Elsevier]

Valproic acid (VPA) is the most effective medication in juvenile myoclonic epilepsy (JME) but, due to its teratogenic potential, levetiracetam (LEV) and lamotrigine (LTG) are preferred in women of childbearing age. The aim of this study was to compare the effectiveness and tolerability of LEV and LTG monotherapy in patients with a previous good seizure control in VPA monotherapy, in which VPA was withdrawn because of teratogenic potential or adverse drug effects. We retrospectively analyzed 65 patients with JME which had been followedup at the Epilepsy Center of Pisa University Hospital, identifying 28 subjects who had been successfully treated with VPA monotherapy and who were shifted to another monotherapy. The second monotherapy was LEV for 14 subjects and LTG for the remaining 14 ones. Drug efficacy was measured in terms of seizure freedom for more than twelve months after reaching the minimum effective or the highest tolerated dose. In terms of seizure control, our analysis showed a significantly better outcome for LEV compared to LTG (14.3% and 71.4% of seizure relapse, respectively, p = 0.006) monotherapy. Such a higher efficacy was confirmed in those subjects with seizure relapse on LTG, who achieved good seizure control after switching to LEV monotherapy (89% of cases). Concerning tolerability, none of the patients reported severe side effects. Although obtained in a small case series, our analysis showed a significant better efficacy of LEV compared to LTG in monotherapy, in patients with JME with a good response to VPA, concerning both myoclonic and generalized tonic-clonic seizures. [ABSTRACT FROM AUTHOR]

Abstract: Stroke is the most common cause of seizures in the elderly. Antiepileptic drugs are used to treat most patients with late poststroke seizures. The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) in patients aged 60 or older with late-onset poststroke seizures. This prospective study evaluated patients 60 years of age or older, who had at least two late-onset poststroke seizures and were given LEV monotherapy. Demographic data and seizure and stroke characteristics were recorded. Outpatient visits were made after 2, 4, 6, 9, and 12 months and every 3 months thereafter, and the effectiveness and tolerability of LEV were investigated. Thirty–four patients with a mean age of 69.76±6.41 were included in this study. Average seizure frequency before treatment was 3.61±3.02/month. Mean follow-up time was 17.68±3.24 months. At daily doses of 1000–2000mg, 82.4% of the patients were seizure free, and 7 patients (20.6%) had side effects. LEV was discontinued in one patient because of severe somnolence. Two patients were switched to another antiepileptic drug because of uncontrolled seizures despite an increase in dose up to 3000mg/day. LEV monotherapy can be effective and well tolerated in elderly patients with late-onset poststroke seizures. [Copyright &y& Elsevier]

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Z ebinix E ffects in DE pendency of BA seline C onditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1 + group), or as add-on to ≥ 2 baseline AEDs (≥ 2 + group). In total, 237 patients were included, 35 in the mono group, 114 in the 1 +, and 88 in the ≥ 2 + group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1 +, and ≥ 2 + group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1 +, and ≥ 2 + groups who were responders (patients with a ≥ 50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1 +, and 28.4% of patients of the ≥ 2 + group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥ 2 + group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups. • Prospective observational study investigating the effectiveness of ESL • Patients with ESL as monotherapy or add-on to 1 or ≥ 2 AEDs observed for 6 months • Groups different in age, treatment refractoriness, and AED use at baseline • ESL retention favorable in all groups, ranging from 75.3% to 93.9% at 6 months [ABSTRACT FROM AUTHOR]

The objective of this study was to describe antiepileptic drug (AED) treatment patterns in patients with epilepsy, with and without psychiatric comorbidities. This was a retrospective claims-based cohort study using Truven Health MarketScan databases (Commercial and supplemental Medicare, calendar years 2012–2017; Medicaid, 2012–2016). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (< 1 year for persons of 1 to < 2 years of age; none for persons < 1 year), and continuous medical and pharmacy enrolment without epilepsy/seizure diagnosis or AED prescription during baseline. Based on presence/absence of psychiatric diagnosis codes in the baseline period, persons were classified into two cohorts: with or without psychiatric comorbidities. Outcomes included percentage of treated persons (AED prescription), type, duration, and outcome of first-line AED treatment. There were 18,062 persons in each cohort with and without psychiatric comorbidities, matched by age, sex, and insurance type, who met selection (or inclusion) criteria. More patients with psychiatric comorbidities were prescribed an AED after diagnosis (57.6% vs. 52.8%), and had at least two AEDs prescribed during follow-up (16.7% vs. 11.4%) than patients without psychiatric comorbidities. Most patients with and without psychiatric comorbidities prescribed AED monotherapy as first-line treatment (73.0% vs. 78.7%). Levetiracetam was the most common AED prescribed less frequently in patients with than without psychiatric comorbidities (40.8% vs. 56.7%). More patients with psychiatric comorbidities changed first-line AED treatment than patients without psychiatric comorbidities. The presence of psychiatric comorbidities may impact treatment decisions in newly diagnosed persons with epilepsy to optimize patient outcomes. • AED treatment patterns in patients with/without psychiatric comorbidities are compared. • First-line AED monotherapy was prescribed for the majority of both patient groups. • The most common first-line AED prescribed for both cohorts was levetiracetam. • Patients with psychiatric comorbidities were treated with more total AEDs. • Treatment patterns differ between patients with and without psychiatric comorbidities. [ABSTRACT FROM AUTHOR]