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August 2020; 10 (4) Review

Clinical utility of therapeutic drug monitoring of antiepileptic drugs

Systematic review

Zanab Al-Roubaie, Elena Guadagno, View ORCID ProfileAgnihotram V. Ramanakumar, Afsheen Q. Khan, View ORCID ProfileKenneth A. Myers
First published September 6, 2019, DOI: https://doi.org/10.1212/CPJ.0000000000000722
Zanab Al-Roubaie
Department of Pharmacology (ZA-R), Faculty of Medicine, Université de Montréal; Research Institute of the McGill University Health Centre (ZA-R, AVR, AQK, KAM), Montréal; Medical Library (EG), McConnell Resource Centre, McGill University Health Centre, Montreal; and Departments of Pediatrics and Neurology & Neurosurgery (KAM), Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
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Elena Guadagno
Department of Pharmacology (ZA-R), Faculty of Medicine, Université de Montréal; Research Institute of the McGill University Health Centre (ZA-R, AVR, AQK, KAM), Montréal; Medical Library (EG), McConnell Resource Centre, McGill University Health Centre, Montreal; and Departments of Pediatrics and Neurology & Neurosurgery (KAM), Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
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Agnihotram V. Ramanakumar
Department of Pharmacology (ZA-R), Faculty of Medicine, Université de Montréal; Research Institute of the McGill University Health Centre (ZA-R, AVR, AQK, KAM), Montréal; Medical Library (EG), McConnell Resource Centre, McGill University Health Centre, Montreal; and Departments of Pediatrics and Neurology & Neurosurgery (KAM), Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
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  • ORCID record for Agnihotram V. Ramanakumar
Afsheen Q. Khan
Department of Pharmacology (ZA-R), Faculty of Medicine, Université de Montréal; Research Institute of the McGill University Health Centre (ZA-R, AVR, AQK, KAM), Montréal; Medical Library (EG), McConnell Resource Centre, McGill University Health Centre, Montreal; and Departments of Pediatrics and Neurology & Neurosurgery (KAM), Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
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Kenneth A. Myers
Department of Pharmacology (ZA-R), Faculty of Medicine, Université de Montréal; Research Institute of the McGill University Health Centre (ZA-R, AVR, AQK, KAM), Montréal; Medical Library (EG), McConnell Resource Centre, McGill University Health Centre, Montreal; and Departments of Pediatrics and Neurology & Neurosurgery (KAM), Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
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Citation
Clinical utility of therapeutic drug monitoring of antiepileptic drugs
Systematic review
Zanab Al-Roubaie, Elena Guadagno, Agnihotram V. Ramanakumar, Afsheen Q. Khan, Kenneth A. Myers
Neurol Clin Pract Aug 2020, 10 (4) 344-355; DOI: 10.1212/CPJ.0000000000000722

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This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Objective To systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.

Methods We searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.

Results Sixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.

Conclusions If optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

  • Received April 11, 2019.
  • Accepted July 19, 2019.
  • © 2019 American Academy of Neurology
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The Nerve!: Rapid online correspondence

  • Author response: Clinical utility of therapeutic drug monitoring of antiepileptic drugs
    • Kenneth A. Myers, Pediatric Neurologist and Epileptologist, Research Institute of the McGill University Health Centre
    Submitted October 26, 2019
  • Reader response: Clinical utility of therapeutic drug monitoring of antiepileptic drugs
    • Nitin K. Sethi, Associate Professor of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY U.S.A.
    Submitted October 09, 2019
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