Randomized controlled antiepileptic drug trials miss almost all patients with ongoing seizures

Steinhoff, Bernhard J.; Staack, Anke M.; Hillenbrand, Barbara

doi:10.1016/j.yebeh.2016.10.025

Cited by 26 publications

(23 citation statements)

References 10 publications

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“…However, while necessary for regulatory approval, the controlled environment and criteria for these types of trials do not account for variabilities that are part of everyday real-world clinical practice. For example, these studies tend to exclude PWE who may be most at risk for BAEs (e.g., patients with a history of comorbid psychiatric conditions), are limited in time and patient exposure to the drug, and often do not allow the use of at least some concomitant medications and supplements, which may influence the incidence and/or severity of BAEs [16,19,20]. Therefore, it is unlikely that these data represent the experience with medications in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

Steinhoff

Klein

Klitgaard

et al. 2021

Epilepsy & Behavior

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“…The Kork Epilepsy Center is one the largest traditional epilepsy centers in Germany offering 122 in-patient beds and more than 6.000 out-patient appointments per year. As a consequence, many of our patients suffer from difficult-to-treat epilepsy syndromes with ongoing seizures in spite of numerous previous therapeutic strategies [3,4]. As soon as a new antiepileptic drug (AED) is marketed many of those patients who have been urgently waiting or a new treatment option will be treated with such a new AED within a relatively short period of time [3].…”

Section: Introductionmentioning

confidence: 99%

Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy—A monocenter survey

Steinhoff

Bacher

Bucurenciu

et al. 2017

Seizure

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“…However, results from regulatory clinical trials are difficult to extrapolate into clinical practice, as these studies are limited by their short duration, and rigid inclusion and exclusion criteria excluding most epilepsy patients, and lack of dosing flexibility . Upon introduction of new AEDs, there is limited information about the potential efficacy and tolerability in a naturalistic clinical setting.…”

mentioning

confidence: 99%

“…9 However, results from regulatory clinical trials are difficult to extrapolate into clinical practice, as these studies are limited by their short duration, and rigid inclusion and exclusion criteria excluding most epilepsy patients, and lack of dosing flexibility. 16,17 Upon introduction of new AEDs, there is limited information about the potential efficacy and tolerability in a naturalistic clinical setting. Therefore, it remains pivotal to assess new AEDs, such as BRV, in terms of their efficacy, tolerability and retention, a robust factor combining both, as well as quality of life and long-term safety, in a real-life setting.…”

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confidence: 99%

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany

et al. 2017

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BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.

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Randomized controlled antiepileptic drug trials miss almost all patients with ongoing seizures

Cited by 26 publications

References 10 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

Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy—A monocenter survey

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany

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