Pharmacology of new and developing intravenous therapies for the management of seizures and epilepsy

ABSTRACT

Introduction: Antiepileptic drugs (AEDs) are administered orally for chronic use. Parenteral formulations might be necessary when the oral route is not feasible (e.g. an impairment of consciousness, trauma, dysphagia, gastrointestinal illness) or for treatment of seizure emergencies. At present, few intravenous (IV) formulations are available on the market.

Areas covered: The purpose of this review is to summarize the pharmacological characteristics and clinical applications of IV medications that have been recently introduced to the armamentarium of epilepsy therapy or are currently being developed. Apart from AEDs, other compounds belonging to different pharmacological classes (e.g. diuretics, anesthetics), which have shown potential effectiveness in seizure control, are taken into consideration, and the pathophysiological premises supporting their use for epilepsy treatment are illustrated. The authors give particular focus to immunomodulatory and immunosuppressive agents, which have become the therapeutic cornerstones for immune-mediated epilepsies, despite regulatory obstacles.

Expert opinion: In several circumstances, especially in the case of seizure-related emergencies, clinical practice seems not match literature-based evidence, and several IV AEDs are still used off-label. Strong evidence derived from randomized clinical trials (RCTs) is needed to support the effectiveness and tolerability of any therapeutic approach, however common and “accepted’ it may be, in order to guarantee patient safety and well-being.

KEYWORDS:

• Autoimmune encephalitis
• immunotherapy
• intravenous
• parenteral
• prophylaxis
• replacement therapy
• status epilepticus

Article highlights

● IV formulations are currently available for some novel and established AEDs, whereas others are under development

● IV preparations allow AED fast titration and complete bioavailability

● Other unconventional, parenteral compounds (e.g. diuretics, immunomodulant agents) are currently being used or investigated as anti-epileptic medications

● IV AEDs are mainly used in seizure emergencies, but also for replacement therapy and seizure prophylaxis after brain trauma/surgery

● Immunotherapies are gaining a paramount importance in the treatment of immune-mediated epilepsies and refractory status epilepticus

This box summarizes key points contained in the article.

Declaration of interest

E Russo has received speaker fees from and has participated in advisory boards for Eisai. He has also received research funding from the Italian Ministry of Health (MoH) and the Italian Medicine Agency (AIFA). Furthermore, C di Bonaventura and AT Giallonardo have received speaker fees from Eisai, UCB Pharma, FB Health and Sandoz. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares they have received speaker fees from Eisai and Phillips. They also have shares in Epilog. Another referee declares having received consultancy fees from UCB Pharma and Eisai.

Additional information

Funding

This manuscript was not funded.