Monotherapy or Polytherapy for First-Line Treatment of SE?

Alvarez, Vincent; Rossetti, Andrea O.

doi:10.1097/wnp.0000000000000217

Cited by 14 publications

(11 citation statements)

References 42 publications

(53 reference statements)

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“…Multiple randomized control studies support the use of benzodiazepines as a first-line treatment for status epilepticus in general. 1 The Rapid Anticonvulsant Medication Prior to Arrival Trial study showed a trend in favor of intramuscular midazolam versus IV lorazepam for initial seizure control (73.4% versus 63.4%), 2 likely reflecting the speed of administration rather than the efficacy of the drug. Benzodiazepines are metabolized predominantly in the liver, and hepatic disease can alter their metabolism.…”

Section: Emergency Treatment Of Seizures In Patients With Liver Diseasementioning

confidence: 99%

Antiepileptic Drugs and Liver Disease

Vidaurre

Gedela

Yarosz

2017

Pediatric Neurology

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Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease. Choosing the most appropriate antiepileptic drug in this setting represents a difficult challenge, as most medications are metabolized by the liver. This article focuses on the acute and chronic treatment of seizures in patients with advanced liver disease and reviews the hepatotoxic potential of specific antiepileptic drugs. Newer antiepileptic drugs without, or with minimal, hepatic metabolism, such as levetiracetam, lacosamide, topiramate, gabapentin, and pregabalin should be used as first-line therapy. Medications undergoing extensive hepatic metabolism, such as valproic acid, phenytoin, and felbamate should be used as drugs of last resort. In special circumstances, as in patients affected by acute intermittent porphyria, exposure to most antiepileptic drugs could precipitate attacks. In this clinical scenario, bromides, levetiracetam, gabapentin, and vigabatrin constitute safe choices. For the treatment of status epilepticus, levetiracetam and lacosamide, available in intravenous preparations, are good second-line therapies after benzodiazepines fail to control seizures. Hepatotoxicity is also a rare and unexpected side effect of some antiepileptic drugs. Drugs such as valproic acid, phenytoin, and felbamate, have a well-recognized association with liver toxicity. Other antiepileptic drugs, including phenobarbital, benzodiazepines, ethosuximide, and the newer generations of antiepileptic drugs, have only rarely been linked to hepatotoxicity. Thus physicians should be mindful of the pharmacokinetic profile and the hepatotoxic potential of the different antiepileptic drugs available to treat patients affected by liver disease.

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Section: Emergency Treatment Of Seizures In Patients With Liver Diseasementioning

confidence: 99%

Antiepileptic Drugs and Liver Disease

Vidaurre

Gedela

Yarosz

2017

Pediatric Neurology

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“…An adult observational prospective study found that administering a combination of BZD (diazepam or clonazepam) with fosphenytoin as first-line treatment leads to a higher rate of SE termination [108]. Though the latest guidelines recommend initial BZD monotherapy with rapid escalation to second-line agents, early polytherapy continues to gain interest as a potential target for investigation [38,105,109].…”

Section: Synergistic Pharmacotherapy and Future Directionsmentioning

confidence: 99%

Pharmacotherapy for Pediatric Convulsive Status Epilepticus

2019

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Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABA A receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-d-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

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“…Median 75 (range, 49-113 months) Median 68 (range, 31.5-93 months) Sex 12 males (57%), 5 females (24%), 3…”

Section: Agementioning

confidence: 99%

“…Furthermore, in both human and veterinary medicine, treatment guidelines for cluster seizures (CS) and status epilepticus (SE) must balance the need for seizure control with the risk of dangerous adverse effects (eg, cardiorespiratory depression) associated with antiepileptic medication (AEM) administration . To enhance the anticonvulsant action of AEMs and decrease the occurrence of adverse effects, the concept of early polytherapy recently has been introduced in human medicine . Although the literature on early combined polytherapy is still limited, it is hypothesized that AEMs with different molecular mechanisms of action can be combined together so as to enhance their anticonvulsant properties …”

Section: Introductionmentioning

confidence: 99%

Open‐label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures

Cagnotti

Odore

Bertone

et al. 2019

Veterinary Internal Medicne

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Background Treatment options for at‐home management of cluster seizures (CS) and status epilepticus (SE) are limited. The pharmacokinetics of levetiracetam (LEV) after rectal administration in both healthy and epileptic dogs has been investigated recently. Hypothesis/Objectives To investigate the clinical efficacy of rectally administered LEV in preventing additional seizures in dogs presented for CS and SE. We hypothesized that rectal administration of LEV in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone. Animals Fifty‐seven client‐owned dogs with CS or SE. Methods Prospective open‐label clinical trial. Patients included in the study were assigned to receive either a standard treatment protocol comprising IV/rectal diazepam and IV phenobarbital q8h (control group) or a standard treatment protocol in association with a single dose of 40 mg/kg LEV rectally (rectal LEV group). Dogs that experienced no additional seizures were defined as responders, whereas those that showed additional seizure activity were classified as nonresponders. Results Twenty‐one dogs were assigned to the rectal LEV group, and 36 to control group. Given the small number of cases of SE, statistical analysis was performed only on patients with CS. The response rate was 94% in the rectal LEV group and 48% in the control group ( P < .001). Conclusions and Clinical Importance Rectally administered LEV combined with a standard treatment protocol provided good control of seizure activity in patients with CS. The validity of these results should be confirmed in a double‐blinded, placebo‐controlled clinical trial.

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Monotherapy or Polytherapy for First-Line Treatment of SE?

Cited by 14 publications

References 42 publications

Antiepileptic Drugs and Liver Disease

Antiepileptic Drugs and Liver Disease

Pharmacotherapy for Pediatric Convulsive Status Epilepticus

Open‐label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures

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