Summary of Antiepileptic Drugs Available in the United States of America

Vossler, David G.; Weingarten, Mindl; Gidal, Barry E.

doi:10.5698/1535-7597.18.4s1.1

Cited by 61 publications

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“… a Common steady state serum concentrations observed in ambulatory epilepsy patients. 29 b Maximum FDA-approved maintenance dose for ambulatory patients with epilepsy. 29 c May be titrated to produce burst suppression pattern (5- to 15-second interburst interval) on continuous electroencephalogram monitoring.…”

Section: Resultsmentioning

confidence: 99%

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Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

et al. 2020

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Purpose: Established tonic–clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. Methods: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process. Results: No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study). Conclusions: Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

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Section: Resultsmentioning

confidence: 99%

“… 29 b Maximum FDA-approved maintenance dose for ambulatory patients with epilepsy. 29 c May be titrated to produce burst suppression pattern (5- to 15-second interburst interval) on continuous electroencephalogram monitoring. d Theoretical loading dose, but ventricular and atrial arrhythmias are a concern.…”

Section: Resultsmentioning

confidence: 99%

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

et al. 2020

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“…Despite more than 30 antiepileptic medication available on the market (1, 2), about 30–40% of patients treated for epilepsy continue to have seizures (3). For these patients with drug-resistant focal epilepsy, surgery constitutes the most promising treatment option in order to achieve seizure freedom (4–6).…”

Section: Introductionmentioning

confidence: 99%

Localization of the Epileptogenic Zone Using High Frequency Oscillations

2019

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For patients with drug-resistant focal epilepsy, surgery is the therapy of choice in order to achieve seizure freedom. Epilepsy surgery foremost requires the identification of the epileptogenic zone (EZ), defined as the brain area indispensable for seizure generation. The current gold standard for identification of the EZ is the seizure-onset zone (SOZ). The fact, however that surgical outcomes are unfavorable in 40–50% of well-selected patients, suggests that the SOZ is a suboptimal biomarker of the EZ, and that new biomarkers resulting in better postsurgical outcomes are needed. Research of recent years suggested that high-frequency oscillations (HFOs) are a promising biomarker of the EZ, with a potential to improve surgical success in patients with drug-resistant epilepsy without the need to record seizures. Nonetheless, in order to establish HFOs as a clinical biomarker, the following issues need to be addressed. First, evidence on HFOs as a clinically relevant biomarker stems predominantly from retrospective assessments with visual marking, leading to problems of reproducibility and reliability. Prospective assessments of the use of HFOs for surgery planning using automatic detection of HFOs are needed in order to determine their clinical value. Second, disentangling physiologic from pathologic HFOs is still an unsolved issue. Considering the appearance and the topographic location of presumed physiologic HFOs could be immanent for the interpretation of HFO findings in a clinical context. Third, recording HFOs non-invasively via scalp electroencephalography (EEG) and magnetoencephalography (MEG) is highly desirable, as it would provide us with the possibility to translate the use of HFOs to the scalp in a large number of patients. This article reviews the literature regarding these three issues. The first part of the article focuses on the clinical value of invasively recorded HFOs in localizing the EZ, the detection of HFOs, as well as their separation from physiologic HFOs. The second part of the article focuses on the current state of the literature regarding non-invasively recorded HFOs with emphasis on findings and technical considerations regarding their localization.

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“…Despite the large number of works on epilepsy pharmacotherapy, a relatively wide range of antiepileptic drugs (AEDs) with different mechanisms of action, including prolonged action, and satisfactory control of seizures is only achieved in 65%-70% of patients (Gesche et al, 2019). In some patients, AEDs cause an increase in the frequency of attacks and the appearance of a large number of side effects, the transformation of attacks, and the deterioration of encephalographic indicators (Janmohamed, 2020;Vossler et al, 2018). Therefore, despite the availability of both well-known and successful developments of new AEDs in recent decades, the search for new compounds that are promising for the treatment of seizures and epilepsy in preclinical and clinical studies has improved efficacy and tolerability (Bialer and White, 2010).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, docking study, and pharmacological evaluation of S-acetamide derivatives of 4,6-dimethyl-2-thiopyrimidine as anticonvulsant agents

Severina¹,

Skupa²,

Волощук³

et al. 2020

J App Pharm Sci

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The aim of this study is the direct synthesis of new (4,6-dimethylpyrimidin-2-yl)thio-N-acetamides derivatives as possible anticonvulsants. The interaction of thiourea with acetylacetone in sodium ethoxide resulted in the scaffold of 4,6-dimethyl-2-thiopyrimidine. Thioacetamide derivatives were synthesized by alkylation of 4,6-dimethyl-2thiopyrimidine with comparable α-chloroacetamides in the Dimethylformamide (DMF) environment and in the presence of К 2 СО 3. The methods of 1 H and 13 C Nuclear magnetic resonance (NMR) spectroscopy, Liquid chromatographymass spectrometry (LS/MS), and elemental analysis established the structure of the synthesized compounds. The affinity of the studied compounds with anticonvulsant biotargets-Type-A γ-aminobutyric acid receptor (GABAAR) and the gamma-aminobutyric acid-aminotransferase enzyme-was carried out using the molecular-docking method. The highest affinity was predicted for the compound having 4-bromophenyl substituent: −7.0 (GABAA) and −8.0 (GABAАТ) kcal/mol. Nevertheless, all the studied compounds conceded to the reference ligands-phenobarbital (−7.6 kcal/mol) and vigabatrin (−9.0 kcal/mol). The model of pentylenetetrazole-induced seizures in rats has shown that the studied compounds have moderate anticonvulsant activity. 4-Bromophenyl acetamide has also shown the most pronounced activity: the substance statistically significantly extended the latency period and reduced the duration of seizures by 3.4 and 2.2 times, respectively; moreover, it reduced lethality of the laboratory animals by 80% and by 2.5 times severity of seizures. Correspondence between the docking results and in vivo studies, using PTZ-induced seizures, as well as some parameters of "structure-anticonvulsant activity" correlation, was determined.

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Summary of Antiepileptic Drugs Available in the United States of America

Cited by 61 publications

References 0 publications

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

Localization of the Epileptogenic Zone Using High Frequency Oscillations

Synthesis, docking study, and pharmacological evaluation of S-acetamide derivatives of 4,6-dimethyl-2-thiopyrimidine as anticonvulsant agents

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