Status epilepticus prognosis following levetiracetam administration: Analysis of loading doses.

BACKGROUND AND PURPOSE: Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored. METHODS: This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose. RESULTS: Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance. CONCLUSIONS: Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic.

Dosage, time, and polytherapy dependent effects of different levetiracetam regimens on cognitive function.

OBJECTIVE: Cognitive impairment is a potential drawback of antiseizure medications. This study aimed to evaluate the impact of different levetiracetam drug regimens on cognitive function. METHODS: A retrospective analysis identified 221 patients diagnosed with seizures who underwent cognitive screening. Patients were categorized into four groups: no medications, non-levetiracetam medications, high and low dose levetiracetam. Composite scores determined low and high levetiracetam groups whereby one point was added for each increment in dosage, duration since uptake, and concurrent anti-seizure medication. Variables known to affect cognition were recorded and classified as demographic, seizure-related, diagnosis-related, and psychopathology. Logistic regression was used to identify variables associated with cognitive scores below cut-off. RESULTS: Multivariable analysis found being male, non-active in the community, less than 12 years of education, left temporal lobe epilepsy, high seizure frequency, and depression were associated with poor cognitive performance. In a final regression analysis, the high levetiracetam group exhibited a 4.5-fold higher likelihood of scoring below cut-off than the medication-free group (OR 4.5, CI 1.5-13.6, p<.08). Depression (OR 2.1, CI 1.1-3.9, p<.03), being male (OR 2.2, CI 1.1-4.3, p<.02), and not being active in the community (OR 3.8, 1.6-8.7, p <.003) remained significant contributors to the model. Language (p<.05), attention (p<.05), and delayed recall (p<.001) were the most affected cognitive domains. SIGNIFICANCE: When taken in small doses, for brief periods as monotherapy, levetiracetam minimally influences cognition. At higher doses, as part of long-term seizure management, in conjunction with multiple ASMs, LEV is associated with cognitive impairment.

Experience of Subcutaneous Levetiracetam in Palliative Care.

BACKGROUND: Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care. OBJECTIVE: The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia. METHODS: We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019-2021. Data were extracted from medical records, and participants were followed up as outpatients. RESULTS: Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days. CONCLUSION: Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.

Pyridoxine for treatment of levetiracetam-induced behavioral adverse events: A randomized double-blind placebo-controlled trial.

BACKGROUND: Levetiracetam is a broad-spectrum antiseizure medication with known behavioral side effects. The possible beneficial effect of pyridoxine on improvement of these psychiatric problems has been suggested in few previous studies. This clinical trial aimed to investigate the effect of pyridoxine on behavioral side effects of levetiracetam in adult patients with epilepsy. METHODS: This study was a randomized double-blind placebo-controlled clinical trial on 53 adult patients with epilepsy with behavioral side effects after treatment by levetiracetam. Patients who met the study criteria were randomized to receive 40 mg/day pyridoxine or placebo. Their psychiatric state was surveyed by SCL-90-R questionnaire before and three weeks after initiation of treatment. RESULTS: There were no statistically significant differences in the behavioral adverse effects between the pyridoxine-treated group and the placebo group. CONCLUSION: Although this study showed no statistically significant beneficial effects of pyridoxine on the behavioral adverse effects of levetiracetam, placebo-controlled trials with a larger size and higher doses are needed to determine whether it is effective or not.

Irritability and its relationship with psychosocial symptoms and quality of life in adolescents with epilepsy receiving levetiracetam therapy: A case-control study.

BACKGROUND: Levetiracetam, a widely used anticonvulsant drug in children and adolescents, has been associated with irritability, psychosocial symptoms, and low quality of life, which are also influenced by other epilepsy variables. PURPOSE: The objective of this study was to investigate the level of treatment-related irritability in adolescents receiving levetiracetam, and to evaluate the relationship between irritability levels and psychosocial symptoms, and quality of life. METHODS: A cross-sectional, case-control study was conducted. Consecutive adolescent patients with epilepsy aged 11-17 years with partial or generalized seizures, treated with either levetiracetam or valproic acid for at least 6 months, and healthy controls were recruited. The Affective Reactivity Index parent report and self-report, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory-Psychosocial subscale were utilized to assess irritability, psychosocial symptoms, and functioning. RESULTS: A total of 120 participants were analyzed; 33 patients in the LEV group, 45 patients in the VPA group, and 42 healthy controls. Both self and parent report irritability levels of the LEV group were found to be significantly higher than those of healthy controls. The irritability levels of the LEV and VPA groups were not statistically different, but still the LEV group had higher irritability levels on both scales. In the LEV group, irritability was positively correlated with behavioral, emotional, and attention/hyperactivity problems, and also negatively correlated with psychosocial quality of life. CONCLUSION: Adolescents with epilepsy using LEV have a high level of irritability and this is associated with some psychosocial symptoms and poor quality of life.

Efficacy of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children.

PURPOSE: Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS). METHODS: In this study, 185 patients diagnosed with CSE or ARS and aged between 1 month and 18 years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated. RESULTS: A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24 h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36 months were significantly related to seizure recurrence (p < 0.01). CONCLUSIONS: Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin.

Regulation of Inflammation-Related Genes through Fosl1 Suppression in a Levetiracetam-Treated Pilocarpine-Induced Status Epilepticus Mouse Model.

Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in Fosl1 expression that occurs after lipopolysaccharide (LPS) stimulation is suppressed by LEV and that Fosl1 inhibition suppresses inflammation in BV-2 microglial cells. These data indicate that Fosl1 is an important target of LEV and a key factor in preventing epilepsy onset. In this study, we examined the effects of LEV on Fosl1 expression and neuroinflammation in vivo. During epileptogenesis, the post-SE upregulation of hippocampal levels of Fosl1 and many inflammatory factors were suppressed by LEV. Fosl1 expression showed a characteristic pattern different from that of the expression of Fos, an immediate-early gene belonging to the same Fos family. At 2 days after SE, Fosl1 was predominantly expressed in astrocytes but was rarely detected in microglia, whereas Fos expression was distributed in various brain cell types. The expression of A2 astrocyte markers was similar to that of Fosl1 and was significantly suppressed by LEV. These results suggest that LEV may regulate astrocyte reactivity through regulation of Fosl1.

Effect of levetiracetam on nocturnal sleep in patients with epilepsy.

AIM OF THE STUDY: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy. CLINICAL RATIONALE: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV's effect on nocturnal sleep architecture. MATERIAL AND METHODS: The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy. RESULTS: Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance. CONCLUSIONS: Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

Rapid administration of undiluted intravenous levetiracetam.

OBJECTIVE: Operational delays have the potential to lead to suboptimal time to seizure control during status epilepticus. Levetiracetam (LEV) is an urgent control antiepileptic medication that offers relative lack of adverse effects and ease of monitoring. There are limited data published demonstrating safety and tolerability of undiluted rapid intravenous (IV) push of LEV in doses of 1000 mg or less. The purpose of this study was to evaluate the safety of IV push administration of LEV doses up to 4500 mg. METHODS: This is a retrospective, observational, cohort analysis of adult patients who received at least one dose of undiluted IV push LEV from October 15, 2019 to August 31, 2020 at a large academic medical center in Phoenix, Arizona. Outcomes of interest include safety and tolerability of rapid administration of undiluted LEV. RESULTS: There were 953 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizure in 51.9% of patients, and 40.7% of patients had a documented history of epilepsy or seizure disorder. There were 8561 undiluted IV push LEV doses administered, 3674 (42.9%) of which were greater than 1000 mg. LEV was administered most often through a peripheral IV (79.1%). There were 12 patients with documented adverse drug events during the study period, with four potentially directly related to IV push LEV administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line. SIGNIFICANCE: Rapid IV administration of undiluted LEV is both safe and tolerable in doses of up to 4500 mg, allowing for rapid drug administration, which is paramount during neurologic emergencies.

Differences in levetiracetam and perampanel treatment-related irritability in patients with epilepsy.

PURPOSE: The present study evaluated whether patients with epilepsy who received both levetiracetam (LEV) and perampanel (PER) therapy showed side effects of irritability. The study also examined the relationship between patient characteristics and irritability when it occurred as a side effect. METHODS: We retrospectively examined medical records of 98 patients with epilepsy who were treated with both LEV and PER at the Department of Psychiatry in the Epilepsy Center of Nishiniigata Chuo National Hospital in Japan. We performed multiple regression analyses with the presence/absence of irritability due to LEV or PER as the dependent variables and clinical characteristics of the patients as independent variables. RESULTS: LEV and PER caused irritability in 7 and 17 of 98 patients, respectively. LEV- and PER-related irritability did not occur in the same patients. A logistic multiple regression analysis revealed that EEG findings of temporal focal epileptic discharge were significantly associated with increased incidence of irritability due to LEV. LEV-related irritability decreased significantly with higher dosages of LEV. Another logistic multiple regression analysis revealed that a psychiatric comorbidity of irritability and EEG findings of nontemporal focal epileptic discharge were significantly associated with increased incidence of irritability due to PER. CONCLUSIONS: LEV and PER cause irritability in different patient groups. Additionally, irritability as a side effect was present only at low dosages of LEV, but PER tended to cause irritability even at high dosages.

Evaluation of Time to Administration, Benzodiazepine Use, and Safety of Intravenous Push Levetiracetam in a Neuro-Spine Intensive Care Unit.

PURPOSE: The purpose of this study was to evaluate the time to medication administration, clinical effect, and safety of a recent Pharmacy and Therapeutics Committee-approved change in the administration of levetiracetam from intravenous piggyback (IVPB) over 15 min to undiluted intravenous push (IVP) over 2-5 min at a large academic medical center. METHODS: The primary outcome was the time from order verification to the administration of IVP levetiracetam versus IVPB levetiracetam. The secondary outcome was any benzodiazepine administered in the time between levetiracetam order verification and administration in both groups. Adult patients admitted to the neuro-spine intensive care unit in the 6 months prior to and after the policy change, and who received at least one dose of 1000 mg or higher of IVP or IVPB levetiracetam for active seizures, were included in this retrospective, observational, institutional review board-approved study. Data were analyzed using descriptive statistics, χ2, and the Mann-Whitney U-test as appropriate. RESULTS: Of the 2055 hospital-wide levetiracetam doses ordered within the study period, 316 doses were screened for enrollment and 160 were enrolled with 60 and 100 patients assigned to the IVP and IVPB groups, respectively. There were no differences between the groups at baseline. The majority of the population was male, 57 years old, had no significant renal dysfunction (defined as a creatinine clearance of less than 60 ml/min), and had a seizure etiology of malignancy or traumatic brain injury. A significant reduction in the time to administration of levetiracetam was found with IVP compared with IVPB administration (28 vs. 80 min, p < 0.0001). A subsequent reduction in patients who received benzodiazepines in the interim of levetiracetam order verification and administration was also associated with IVP compared with IVPB (2% vs. 13%, p = 0.042). There were no differences found in the rates of adverse effects between groups. CONCLUSIONS: Administration of levetiracetam doses up to 2000 mg via IVP is a safe method of administration that results in a reduction of time to medication administration and a reduction of benzodiazepine use.

Behavioral alterations associated with levetiracetam in pediatric epilepsy.

Levetiracetam (LEV) has an improved pharmacological profile and is one of the most commonly used antiepileptic drugs (AEDs). However, associations between this pharmacological profile and behavioral side effects have been extensively reported in pediatric populations. We assessed behavioral changes after initiation of LEV, prescribed by the treating neurologist, in Chilean patients with epilepsy aged 4-15 years. A behavioral questionnaire was applied at baseline and at two, four, and twelve weeks of treatment. Thirty patients were enrolled: 16 males, 14 females, average age 8 years (range: 4-14). By week four, 23.3% of patients showed significant behavioral alterations that persisted throughout the observation period. No significant alterations emerged after four weeks in the remaining patients. Family history of psychiatric disease and prior behavioral difficulties were predisposing factors for adverse behavioral effects. Although previous studies associated adverse behavioral effects with LEV in pediatric patients with epilepsy, we believe that this is the first study to use a prospective methodology and standardized tools to quantify the symptomatology. Adverse behavioral effects may significantly affect quality of life for patients and families, diminishing the tolerability of treatment. To ensure successful therapy and improve medical decision-making, it is essential to consider predisposing factors for drug-related adverse effects and to regularly assess for behavioral alterations during treatment.

Therapeutic effect of piracetam with nimodipine on vascular dementia after cerebral infarction.

This article investigated the clinical effects of piracetam with nimodipine in the treatment of vascular dementia (VD) after cerebral infarction. 98 patients with vascular dementia after cerebral infarction were selected and divided into the control group and the study group according to the treatment method. The control group was treated with nimodipine alone. The study group was treated with piracetam on the basis of this observation, and we test the ADL (life ability score), MoCA(montreal cognitive assessment scale), ADAS-Cog(alzheimer's scale-cognition), MMSE(mental status examination) scores and quality of life scores before and after treatment in the two groups. Before treatment, there were no significant differences in ADL, MoCA, and ADAS-Cog scores between the two groups (P>0.05). After treatment, the ADL, MoCA, and ADAS-Cog scores of the study group were superior to the control group. The difference was statistically significant (P<0.05). There was no significant difference in MMSE scores between the two groups before treatment and 1 month after treatment (P>0.05). The MMSE scores of the study group were better than the control group after 3 months of treatment and half a year after treatment. The difference was statistically significant (P <0.05). Before treatment, there was no significant difference in the quality of life scores between the two groups (P>0.05). After treatment, the quality of life scores was significantly higher than the control group, and the difference was statistically significant (P<0.05). For patients with vascular dementia after cerebral infarction, piracetam combined with nimodipine can improve the cognitive function, improve the quality of life, and have a significant clinical effect.

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.

Population pharmacokinetic model of levetiracetam in Korean neonates with seizures
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OBJECTIVE: This study was conducted to develop a population pharmacokinetic (PK) model of levetiracetam in Korean neonates with seizures. MATERIALS AND METHODS: Data were obtained from a retrospective study of 18 neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of Severance Children's Hospital for the period of from 2013 to 2015. Sampling and dosing times were recorded by clinical research coordinators on case report forms. Demographic factors and laboratory results were tested as potential covariates for PK parameters. Model development was performed within a mixed-effect modeling framework using NONMEM. RESULTS: With a one-compartment model with first-order elimination chosen as a basic PK model based on theory-based allometric relationships, postmenstrual age and serum creatinine were found to have significant influences on clearance (CL). Typical parameter estimates of the final PK model obtained, evaluated at covariate medians, were 1.08 L/kg for volume of distribution (V) and 0.073 L/h/kg (= 1.23 mL/min/kg) for CL, illustrating that V in Korean neonates is a little larger than in Western population while CL is similar. CONCLUSION: A population PK model of levetiracetam for Korean neonates with seizures was developed in this study. The result of this study can be used as a basis to develop an optimal dosage regimen in Korean neonates with seizures.
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A meta-analysis of the effect of different neuroprotective drugs in management of patients with traumatic brain injury.

Traumatic brain injury is a major problem worldwide. Our objective is to synthesize available evidence in the literature concerning the effectiveness of neuroprotective drugs (cerebrolysin, citicoline, and piracetam) on Glasgow outcome score (GOS), cognitive performance, and survival in traumatic brain injury patients. Comprehensive search of electronic databases, search engines, and conferences proceedings; hand search journals; searching reference lists of relevant articles, theses, and local publications; and contact of authors for incomplete data were performed. Studies included patients in all age groups regardless of severity of trauma. There was no publication date restriction. Two reviewers independently extracted data from each study. Fixed effect or random effects model selection depends on results of statistical tests for heterogeneity. The literature search yielded 13 studies. Patients treated with cerebrolysin (n = 112) had favorable GOS three times more than controls (OR 3.019; 95 % CI 1.76 to 5.16; p = 0.003*). The odds of cognition improvement in the treatment group was 3.4 times more than controls (OR 3.4; 95 % CI 1.82 to 5.21; p < 0.001*). Survival of cerebrolysin-treated patients did not differ from controls (103 patients; OR = 2.81; 95 % CI 0.905 to 8.76). Citicoline did not improve GOS (1355 patients; OR 0.96; 95 % CI 0.830 to 1.129; p = 0.676), cognitive performance (4 studies; 1291 patients; OR 1.35; 95 % CI 0.58 to 3.16; p = 0.478), and survival (1037 patients; OR = 1.38; 95 % CI 0.855 to 2.239). One study showed a positive effect of piracetam on cognition. Further research with high validity is needed to reach a solid conclusion about the use of neuroprotective drugs in cases of brain injury.

Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network.

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy.

OBJECTIVE: To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB. METHODS: In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period). The primary outcome was retention rate on LCM. RESULTS: Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued their SCB after cross-titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%). CONCLUSIONS: In patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB down-titration and stable background LEV-could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB.