Brivaracetam in adults with drug-resistant epilepsy and psychiatric comorbidities

Theochari, Evangelia; Cock, Hannah R.; Lozsádi, Dora A.; Galtrey, Clare; Arevalo, Jan; Mula, Marco

doi:10.1016/j.yebeh.2018.11.032

Cited by 31 publications

(24 citation statements)

References 19 publications

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“…Aggression was reported for 4.4% (weighted mean; range, 1.0-24.5 %) of patients treated with PER, 2.6% (range, 1.4-20.0%) treated with LEV, and 2.5% (range, 1.0-12.0%) treated with BRV [9,30,32,33,36,37,40,41,44,47,48,[50][51][52][61][62][63][64][65][66][67].…”

Section: Incidences Of Irritability Anger and Aggressionmentioning

confidence: 99%

“…Five studies (4 retrospective studies and 1 prospective observational study) reported the incidences of BAEs and psychiatric adverse events in a subset of patients (n = 156) after a switch from LEV to BRV because of tolerability or specifically because of BAEs or psychiatric adverse events (Table 4) [32,36,37,67,70]. Overall, 66.6% (weighted mean; range, 33.3-83.0%) of patients experienced improvement in BAEs after switching from LEV to BRV.…”

Section: Incidences Of Behavioral Adverse Events In Patients Switching From Lev To Brvmentioning

confidence: 99%

“…Hirsch et al demonstrated an improvement in the incidence of irritability/aggressiveness from 27% during LEV treatment to 8% after the switch to BRV [70]. The retrospective study by Theochari et al demonstrated that 77% of patients (n = 10/13) with depression and/or aggressive behavior while on LEV did not experience BAEs or psychiatric adverse events while taking BRV, although 2 (15%) did report aggressive behavior only and 1 (8%) reported depression and aggressive behavior [67]. The retrospective analysis by Steinig and colleagues revealed that BAEs presented under previous LEV treatment improved on switching to BRV in 57.1% (20/35) of patients [70].…”

Section: Incidences Of Behavioral Adverse Events In Patients Switching From Lev To Brvmentioning

confidence: 99%

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Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review

Steinhoff

Klein

Klitgaard

et al. 2021

Epilepsy & Behavior

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To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV. Methods: A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively. Results: A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%).*Denotes only 1 study.

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Section: Incidences Of Irritability Anger and Aggressionmentioning

confidence: 99%

Section: Incidences Of Behavioral Adverse Events In Patients Switching From Lev To Brvmentioning

confidence: 99%

Section: Incidences Of Behavioral Adverse Events In Patients Switching From Lev To Brvmentioning

confidence: 99%

See 1 more Smart Citation

Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review

Steinhoff

Klein

Klitgaard

et al. 2021

Epilepsy & Behavior

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“…144 In another series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities, depression, and aggressive behavior were reported in 8% each under add-on BRV, but in 77% of patients who had psychiatric adverse events under LEV, this did not happen with BRV. 145 In a prospective controlled study in 37 patients anger levels, depression-anxiety and quality of life were assessed by standardized tools prior to and under BRV add-on treatment. Anger levels, mood scores and quality of life improved with BRV irrespective of prior use of LEV.…”

Section: Side Effects/adverse Reactions and Toxicologymentioning

confidence: 99%

Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience

Steinhoff

Staack

2019

Ther Adv Neurol Disord

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Until the early 1990s, a limited number of antiepileptic drugs (AEDs) were available. Since then, a large variety of new AEDs have been developed and introduced, several of them offering new modes of action. One of these new AED families is described and reviewed in this article. Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate compounds binding at the presynaptic SV2A receptor site and are thus representative of AEDs with a unique mode of action. LEV was extensively investigated in randomized controlled trials and has a very promising efficacy both in focal and generalized epilepsies. Its pharmacokinetic profile is favorable and LEV does not undergo clinically relevant interactions. Adverse reactions comprise mainly asthenia, somnolence, and behavioral symptoms. It has now been established as a first-line antiepileptic drug. BRV has been recently introduced as an adjunct antiepileptic drug in focal epilepsy with a similarly promising pharmacokinetic profile and possibly increased tolerability concerning psychiatric adverse events. This review summarizes the essential preclinical and clinical data of LEV and BRV that is currently available and includes the experiences at a large tertiary referral epilepsy center.

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“…Moreover, prior use of LEV or the presence of a psychiatric background did not influence the results. In a recent case-series study involving 25 patients with drug-resistant epilepsy and psychiatric co-morbidities, 77% patients who developed PAEs with LEV did not do so on BRV, suggesting that BRV is better tolerated in patients with psychiatric co-morbidities 68. Lastly, in a recent animal study using a Kainic Acid Model, BRV-treated rats displayed significantly less aggressive behaviors (ie, they behaved like the control group) than LEV-treated rats 69.…”

Section: Clinical Trialsmentioning

confidence: 98%

<p>Brivaracetam in the treatment of epilepsy: a review of clinical trial data</p>

Feyissa

2019

NDT

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Brivaracetam (BRV), an analog of levetiracetam (LEV), was discovered during a target-based rational drug discovery program that aimed to identify potent synaptic vesicle protein 2A (SV2A) ligands. Among the 12,000 compounds screened in vitro, BRV was found to have 15–30 times greater affinity for SV2A and faster brain permeability than LEV. Although preclinical and post-marketing studies suggest broad spectrum of efficacy, BRV is currently only approved as monotherapy and adjunctive therapy of focal-onset seizures in patients age 4 years and older. This review examines the use of BRV as add‐on (5–200 mg/day) therapy for epilepsy with a particular emphasis on the six regulatory randomized clinical trialsinvolving 2399 participants. Participants receiving BRV add‐on at doses of 50–200 mg/day were more likely to experience a 50% or greater reduction in seizure frequency (pooled risk ratio [RR]) 1.79 with 95% CI of 1.51–2.12) than those receiving placebo. Participants receiving BRV were also more likely to attain seizure freedom (57 [3.3%] vs 4 [0.5%]; RR 4.74, 95% CI 2.00–11.25) than those receiving placebo. In addition, BRV demonstrated a favorable safety profile similar to placebo across all BRV doses. Treatment emergent adverse events significantly associated with BRV were irritability, fatigue, somnolence, and dizziness. Post-hoc analysis of regulatory trials, post-marketing studies, and indirect comparison meta-analyses demonstrated equivalent efficacy and better tolerability of BRV when compared to other antiseizure drugs. Further, these studies appear to suggest that behavioral adverse events are likely to be less frequent and less severe with BRV than LEV. Therefore, switching to BRV may be considered for patients who have seizure control with LEV, but who cannot tolerate its behavioral adverse effects. In this setting, immediate switch from LEV to BRV at a 10:1–15:1 ratio without titration is feasible. Further research is needed to examine the long-term tolerability and efficacy of BRV as well as its role in the treatment of other types of epilepsies, particularly dementia-related epilepsy and brain tumor-related epilepsy.

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Brivaracetam in adults with drug-resistant epilepsy and psychiatric comorbidities

Cited by 31 publications

References 19 publications

Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review

Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review

Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience

<p>Brivaracetam in the treatment of epilepsy: a review of clinical trial data</p>

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