Drugs & Therapy Perspectives

, Volume 35, Issue 10, pp 500–517 | Cite as

Revisiting clinical practice in therapeutic drug monitoring of first-generation antiepileptic drugs

  • Shery JacobEmail author
  • Anroop B. Nair
  • Jigar Shah
Review Article


Due to the complex and diverse nature of epilepsy and antiepileptic drugs (AEDs), the implementation of therapeutic drug monitoring (TDM) can contribute significantly to the overall improvement of clinical outcome in epilepsy. Establishing and interpreting an individual serum drug concentration range by TDM is beneficial to prevent recurrence of epilepsy, as well as to avoid adverse drug effects. It enables optimization of dosage regimen, especially in case of drugs that follow non-linear pharmacokinetics, and in special populations such as pregnancy, pediatrics, geriatrics, critically ill, and liver and renal impairment. This review summarizes the ongoing clinical practice utilizing TDM of first-generation or conventional AEDs, such as valproic acid, phenytoin, carbamazepine, phenobarbital, primidone, ethosuximide, clonazepam, clobazam, piracetam, and sulthiame. Prospective and retrospective data describing the serum drug concentration–efficacy–toxicity relationship, pharmacokinetic parameters, activity of metabolites, overdose and treatment, and drugs that alter pharmacokinetics, have been described. The therapeutic decision should not be finalized based on serum drug concentration alone; other important factors to be considered are clinical laboratory data, patient history, signs and symptoms, pharmacogenetics, and electroencephalogram.


Authorship contributions

SJ designed, drafted, and critically reviewed the manuscript; ABN participated in designing the study and critically reviewed the manuscript; JS contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

S. Jacob, A. B. Nair and J. Shah have no conflicts of interest that are directly related to the content of this work.


No sources of funding were used to conduct this study or prepare this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.College of Pharmacy, Department of Pharmaceutical SciencesGulf Medical UniversityAjmanUnited Arab Emirates
  2. 2.College of Clinical Pharmacy, Department of Pharmaceutical SciencesKing Faisal UniversityAl-AhsaSaudi Arabia
  3. 3.Institute of Pharmacy, Department of PharmaceuticsNirma UniversityAhmedabadIndia

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