ucb-34714 and Mental-Disorders

To comprehensively evaluate the adverse events (AEs) significantly associated with brivaracetam (BRV) treatment in a large selection of randomized control trials.. We conducted an online database search using Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for all available randomized control trials (RCTs) that investigated the therapeutic effects of brivaracetam. Serious AEs (SAEs), withdrawal, and treatment-emergent adverse effects were then assessed for their association with brivaracetam. Finally, a meta-analysis was performed using Review Manager 5.3 software.. Eight RCTs with a total of 2505 patients were included in our study, 1178 of which were randomized with respect to brivaracetam (BRV). Serious AEs, overall withdrawal, AE-related withdrawal and psychiatric adverse events (PAEs) were not significantly associated with BRV treatment. BRV was also not significantly associated with a heightened risk of AE-related withdrawal and PAEs with increasing doses. Of the 17 AEs included in our meta-analysis, three AEs (dizziness, fatigue, and back pain) were found to be significantly associated with BRV treatment. But we did not find that the risk of them was obviously increasing with the increasing doses.. This meta-analysis showed that BRV treatment was reasonably tolerated by patients and rarely caused serious AEs. Further clinical studies will be needed to more concretely determine the safety and tolerability profile of BRV.

Topics: Anticonvulsants; Databases, Bibliographic; Epilepsy; Female; Humans; Male; Mental Disorders; Pyrrolidinones; Randomized Controlled Trials as Topic

We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving levetiracetam (LEV) who switched to brivaracetam (BRV). Patients ≥16 years of age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an open-label Phase 3b study (NCT01653262) comprising a ≤1-week screening period, an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week treatment period. The percentages of patients with investigator-assessed clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and change in health-related quality of life (HRQoL) (Patient-Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed. Of 29 patients enrolled, 26 (89.7%) completed the study. At the end of the treatment period, 27/29 (93.1%) patients switched to BRV had clinically meaningful reductions in BAEs. Physicians reported a reduction in the maximum intensity of primary BAEs in 27/29 (93.1%) patients. Mean change from baseline to Week 12 in QOLIE-31-P total score was 12.1, indicating improved HRQoL. During the treatment period, 23/29 (79.3%) patients reported treatment-emergent adverse events (TEAEs). One patient reported a serious TEAE (suicidal ideation and suicide attempt). Two patients discontinued BRV because of TEAEs. Findings from this small study suggest that patients experiencing BAEs associated with LEV may benefit from switching to BRV.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Prospective Studies; Pyrrolidinones; Quality of Life; Suicidal Ideation; Suicide, Attempted; Treatment Outcome; Young Adult

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5-26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no signifi

Topics: Adolescent; Adult; Aged; Anticonvulsants; Behavioral Symptoms; Comorbidity; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Intellectual Disability; Levetiracetam; Male; Mental Disorders; Middle Aged; Prospective Studies; Pyrrolidinones; Treatment Outcome; Young Adult

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities who started on brivaracetam (BRV) at St George's University Hospitals and Frimley Health in London. Median BRV dose was 150 mg for a median follow-up period of 8 months. Twenty had focal epilepsy, four had generalized epilepsies, and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior, and 12% psychoses. Forty percent of patients presented at least 50% seizure reduction, but none of them became seizure-free. A total of 44% of patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy, and 4% because of both. Depression was reported by 8%, aggressive behavior by 8%, while 4% reported both. A total of 91.6% had received levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. Seventy-seven percent of patients who developed PAEs with LEV did not do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the synaptic vesicle glycoprotein 2A (SV2A) protein modulation is unlikely to be implicated in LEV-related PAEs.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Autism Spectrum Disorder; Comorbidity; Drug Resistant Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; London; Male; Mental Disorders; Middle Aged; Pyrrolidinones; Retrospective Studies; Seizures; Young Adult

The rate of brivaracetam-related behavioural adverse events is a current focus of discussion. This study aims to assess the effect of brivaracetam on anger levels in patients with epilepsy, adjusted by mood symptoms, history of psychiatric disorders and seizure response.. Prospective analysis of 37 patients assessed for anger levels (STAXI-2), depression-anxiety (HADS) and quality of life (QOLIE-10) before adjunctive brivaracetam treatment and reassessed 3-6 months later. A control group following the same protocol of assessment was used for 1:1 comparison. A high percentage of mood stabilisers were included in this control group.. Brivaracetam was indicated for patients including focal onset (79%) and generalised epilepsies (21%). Nearly 60% of responders and no psychiatric adverse events were found. This was similar to controls. The overall results revealed that brivaracetam was assoiciated with better in anger levels, mood scores and quality of life at baseline. Prior use of levetiracetam or the presence of a psychiatric background did not influence the results. However, improvements in anger levels were seen in the brivaracetam responders.. This study shows that brivaracetam is not associated with an increased level of anger in patients with either focal or generalised epilepsies in the absence of psychiatric comorbidity. However, an improvement in anger levels is possibly influenced by a good seizure response.

Topics: Adult; Anger; Anticonvulsants; Comorbidity; Epilepsy; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Pyrrolidinones; Quality of Life; Treatment Outcome

To assess short-term and longer-term effects of brivaracetam (BRV) on cognition and behavior in a naturalistic clinical setting.. Analyses were based on 43 patients with epilepsy who had undergone a neuropsychological screening before adjunctive treatment with BRV and a follow-up evaluation either after 5 days or 25 weeks. The standard assessment focused on reaction times (Neurocog FX), attention and executive functions (EpiTrack), and verbal memory (short version of the VLMT). Self-perceived cognition and behavior was evaluated by an extended version of the Adverse Events Profile. In addition, health-related quality of life (QOLIE-10) was reassessed at the longer-term interval.. Repeated measures analysis of variance revealed a significant improvement under BRV with regard to attention and executive functions (p = .03) without an interaction with the length of the observation interval. A statistical trend in the same direction was also seen for the reaction times (p = .07), but not for the unchanged verbal memory performance. Subjective measures indicated improvements in concentration (p = .02) and especially in comprehension (p < .001), and health-related quality of life (p = .002). Mood and aggression scores were unchanged. At the longer-term follow-up, an at least 50 percent reduction in seizure frequency was observed in 53% of the patients, 21% were seizure free.. These preliminary data point to a favorable cognitive profile of BRV similar to its precursor levetiracetam. Objective gains in attention and executive functions were accompanied by self-reported improvements in concentration and comprehension. Future studies with larger sample sizes and better control conditions are needed to confirm these findings.

Topics: Adult; Anticonvulsants; Attention; Cognition Disorders; Epilepsy; Executive Function; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Photic Stimulation; Pyrrolidinones; Quality of Life; Reaction Time; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult