The Impact of Plasmapheresis on Serum Concentrations of Antiseizure Medications: A Systematic Review

Abstract

Seizures are an important neurological manifestation of several autoimmune and antibody-mediated disorders and often require treatment with antiseizure medications (ASMs). Therapeutic plasma exchange (TPE) is frequently used to treat these antibody-mediated conditions by removing circulating pathogenic factors. However, TPE is non-selective and may also remove protein-bound ASMs, particularly those with low volume of distribution. This unintended drug clearance may result in subtherapeutic concentrations and breakthrough seizures. This study aims to systematically assess the available evidence on the effects of TPE on ASM serum concentrations. It also seeks to determine whether drug removal is clinically significant and needs post-procedure supplemental dosing. A systematic literature search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library from April to May 2025 using predefined MeSH terms and keywords related to epilepsy, ASMs, and TPE. Randomized trials and case reports/series involving patients receiving ASMs concomitantly with TPE and reporting serum drug concentrations were included. Two independent reviewers performed study selection, data extraction, and quality assessment using the Joanna Briggs Institute checklist, in accordance with PRISMA guidelines. The primary outcome was the effect of TPE on ASM serum concentrations and the need for dose adjustment. Eighteen studies comprising 30 patients were included. Phenytoin was the most frequently evaluated ASM; although total serum concentrations often declined during TPE, overall drug removal was generally low, and free levels frequently remained therapeutic. Phenobarbital showed minimal change, while valproate and several newer ASMs demonstrated variable reductions in serum concentrations. Breakthrough seizures were reported in seven studies, ranging from transient events to refractory seizures requiring dose adjustments or treatment discontinuation. The effect of TPE on ASM pharmacokinetics was found to be drug-specific and largely influenced by protein binding and volume of distribution. Although overall drug removal is generally limited, peri-procedural serum fluctuations may contribute to breakthrough seizures in vulnerable patients. Routine supplemental dosing is not generally recommended; instead, individualized monitoring, and post-session dosing strategies are advised, particularly for ASMs with low volume of distribution or in high-risk patients.