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Background: Antiseizure medications remain the cornerstone of treatment for epilepsy, although a proportion of individuals with the condition will continue to experience seizures despite appropriate therapy. Treatment choices for epilepsy are based on variables related to both the individual patient and the available medications. Brivaracetam is a third-generation agent antiseizure medication. Methods: We carried out a Delphi consensus exercise to define the role of brivaracetam in clinical practice and to provide guidance about its use as first add-on ASM and in selected clinical scenarios. A total of 15 consensus statements were drafted by an expert panel following review of the literature and all were approved in the first round of voting by panelists. The consensus indicated different clinical scenarios for which brivaracetam can be a good candidate for treatment, including first add-on use. Results: Overall, brivaracetam was considered to have many advantageous characteristics that render it a suitable option for patients with focal epilepsy, including a fast onset of action, favorable pharmacokinetic profile with few drug-drug interactions, broad-spectrum activity, and being well tolerated across a range of doses. Brivaracetam is also associated with sustained clinical response and good tolerability in the long term. Conclusions: These characteristics also make it suitable as an early add-on for the elderly and for patients with post-stroke epilepsy or status epilepticus as highlighted by the present Delphi consensus. [ABSTRACT FROM AUTHOR]

Objective: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug‐resistant focal epilepsy. Methods: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6‐month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment‐related variables were assessed by using a stepwise logistic regression model. Results: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re‐assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow‐up, whereas no association was identified with sociodemographic and epilepsy‐related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6‐month re‐assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two‐fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes. Significance: Almost 1 in 5 adults with drug‐resistant focal epilepsy who screen negative for depression become positive when re‐assessed 6 months after a treatment change. At re‐assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline. [ABSTRACT FROM AUTHOR]

Objective: There are few comparative data on the third‐generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add‐on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan–Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)‐naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17–3.29) and PER groups (HR = 1.64, 95% CI = 1.06–2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71–16.61), as well as PER‐treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05–2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] =.08, 95% CI =.01–.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV‐naïve (OR = 10.32, 95% CI = 1.55–68.78) versus men. PER (OR = 6.93, 95% CI = 3.32–14.44) and BRV in LEV‐naïve patients (OR = 6.80, 95% CI = 2.64–17.52) had a higher chance of AEs than LCM. Significance: Comparative evidence from real‐world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add‐On First Italian Network Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12‐month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5–20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. Results: A total of 994 participants were included. During the 1‐year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5–20, and >20 seizures per month (p <.001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p <.001). SSR was reached by 51.2% and 26.5% participants with a history of 1–5 and ≥6 ASMs (p <.001); the corresponding rates of SSF were 24.7% and 4.5% (p <.001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p <.001), and in participants with history of ≥6 prior ASMs compared to those with history of 1–5 ASMs (19.6% vs. 12.2%, p =.002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. Significance: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy. [ABSTRACT FROM AUTHOR]

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real‐world practice. Patients with focal epilepsy prescribed add‐on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12‐month follow‐up. Nine hundred ninety‐four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1‐year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure‐free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy. [ABSTRACT FROM AUTHOR]

The study assessed the clinical response to add‐on brivaracetam (BRV) in real‐world practice by means of time‐to‐baseline seizure count methodology. Patients with focal epilepsy who were prescribed add‐on BRV were identified. Primary endpoint was the time‐to‐baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three‐hundred eighty‐seven patients were included. The overall median time‐to‐baseline seizure count was 150 (95% confidence interval [CI] = 130‐175) days. The median time‐to‐baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV‐naive patients, 126 (95% CI = 105‐150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128‐291) days for patients who discontinued LEV due to adverse events (P =.002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02‐1.13, P =.009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001‐1.008, P =.028) were independently associated with the primary endpoint. Add‐on BRV improved seizure control in LEV‐naive and LEV‐prior patients. The time‐to‐baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs. [ABSTRACT FROM AUTHOR]

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care. [ABSTRACT FROM AUTHOR]

Summary: Objective: Although many studies have attempted to describe treatment outcomes in patients with drug‐resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug‐resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. Methods: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug‐resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). Results: A seizure‐free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug‐resistant by the EP. Significance: This study validates the use of ILAE treatment outcome criteria in a real‐life setting, providing validated estimates of seizure freedom in patients with drug‐resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases. [ABSTRACT FROM AUTHOR]