A systematic review of second line therapies in toxic seizures

Abstract

Background

Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures.

Methods

We searched PubMed, Embase, PsychINFO, Cochrane Library, Web of Science, Google Scholar, and International Pharmaceutical Abstracts from inception through August of 2018, following PRISMA Guideline. The MESH terms focused on identifying treatments for seizures induced by drugs or other potentially toxic substances. We excluded the articles if they involved animals, had seizures resulting from alcohol withdrawal, were case reports, or not peer-reviewed. Our primary outcome was seizure termination and/or suppression by the second-line agent as agreed upon by two authors. We used descriptive statistics for analysis.

Results

We identified six case series that met inclusion and exclusion criteria. Included case series contained nine to 235 patient cases each. The most common xenobiotic exposures were bupropion, isoniazid, and anti-psychotics. The description of seizure type and duration was diverse. First-line treatments were primarily benzodiazepines. Secondary treatments included propofol, barbiturates, phenytoin, valproic acid, and levetiracetam. Patient outcomes differed, attributable to any of the following: mixed toxic substances, drug–drug interactions, inability to control seizures, or toxicity of the anti-epileptic drugs (AED) themselves. Few cases specifically discussed the success of secondary treatment administration to suppress or terminate seizures.

Conclusions

Available literature discussing second-line treatment for toxic seizures is of poor quality with high heterogeneity. Although the majority of articles used similar second-line agents, it is difficult to compare the efficacy of the regimens. Additional studies are necessary to identify the most efficacious second-line therapies in toxic seizures.

Keywords:

• Drug-induced seizure
• toxic seizure
• anti-epileptic
• benzodiazepine
• second-line therapy

Disclosure statement

Dr. Seifert is Editor in Chief of Clinical Toxicology. This manuscript was routed to a senior editor to act as Editor in Chief for this submission.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.