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  1. Home
  2. Books
  3. Antiepileptic Drugs
  • Cited by 3
Publisher:
Cambridge University Press
Online publication date:
September 2009
Print publication year:
2005
Online ISBN:
9780511545023
DOI:
https://doi.org/10.1017/CBO9780511545023
Subjects:
Neurology and Clinical Neuroscience, Medicine
Information

Book description

This book reviews the use of antiepileptic drugs focusing on the interactions between these drugs and between antiepileptics and other drugs. These interactions can be beneficial or can cause harm. The aim of this book is to increase awareness of the possible impact of combination pharmacotherapies. Pharmacokinetic and pharmacodynamic interactions are discussed supported by clinical and experimental data. The book consists of five sections covering the general concepts and advantages of combination therapies, the principles of drug interactions, the mechanisms of interactions, drug interactions in specific populations or in patients with co-morbid health conditions, and concludes with a look at the future directions for this field of research. The book will be of interest to all who prescribe antiepileptics to epileptic and non-epileptic patients, including epileptologists, neurologists, neuro-pediatricians, psychiatrists and general practitioners.

Reviews

'The book contains a wealth of information both for everyday practice and for more theoretical aspect. Interactions between AED … covered in great detail. … Why is this book so important? The authors explain it in their foreword. As a substantial proportion of patients with epilepsy will not become seizure free with one drug, combination therapy is necessary and therefore often used.'

Source: Official Journal of the European Paediatric Neurology Society

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Contents

Page 2 of 2

Contents
  • 21 - Drug monitoring in combination therapy
    pp 392-402
    • By Walter Fröscher, Department of Neurology and Epileptology, Die Weissenau (Department of Psychiatry I, University of Ulm), Ravensburg, Germany
  • View abstract

    Summary

    This chapter discusses the applicability of therapeutic drug monitoring during combination therapy with different antiepileptic drugs (AEDs) or during combination of an AED and drugs used for the treatment of non-epilepsy-related conditions relating to three main considerations. AED underdosage may be induced by the addition of a drug which has been indicated for a non-epilepsy-related condition. When combination therapy is associated with symptoms of intoxication, the clinical features and the electroencephalogram (EEG) are often not the right tools to ascertain which AED is responsible. The essential prerequisite for monitoring serum concentrations, both in monotherapy and in combination therapy, is the reliability of the assay methodology. The effectiveness of serum concentration determination depends on the accuracy of the therapeutic ranges of the individual AEDs. Monitoring is essential for drugs with a narrow therapeutic index and for those drugs with unacceptable incidence of toxicity.
  • 22 - Cognitive side-effects due to antiepileptic drug combinations and interactions
    pp 403-418
    • By Albert P. Aldenkamp, Department of Neurology, University Hospital of Maastricht, The Netherlands; Department of Behavioral Science, Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands; University of Amsterdam, SCI Kohnstamm Research Institute, Amsterdam, The Netherlands, Mark de Krom, Department of Neurology, University Hospital of Maastricht, The Netherlands, Irene Kotsopoulos, Department of Neurology, University Hospital of Maastricht, The Netherlands, Jan Vermeulen, Epilepsy centre SEIN, Heemstede, The Netherlands
  • View abstract

    Summary

    This chapter reviews some of our knowledge about a specific subgroup of central nervous system (CNS)-related chronic side-effects of antiepileptic drug (AED) treatment, that is, cognitive side-effects: the adverse effects of drug treatment on information-processing systems. Cognitive AED effects may be examined through an analysis of the relationship between test scores of subjects and their individual serum drug levels, and this approach seems to offer a way out of the problem. Although the psychometric studies generally show a tendency of cognitive impairments in polytherapy compared to monotherapy, this merely suggests a drug interaction effect. Systematic analysis of subjective patients complaints about side-effects of AEDs show that the impact of side-effects may be larger than hitherto suspected both in number of patients involved and the frequency of the complaints. Formal psychometric studies are much more difficult to interpret, especially when formal scientific standards in line with evidence-based medicine are applied.
  • 23 - Selection of drug combinations in clinical practice: current and future perspectives
    pp 421-440
    • By Jerzy Majkowski, Center for Epilepsy Diagnosis and Treatment, Foundation of Epileptology, Warsaw, Poland
  • View abstract

    Summary

    This chapter discusses polytherapy with old and new antiepileptic drugs (AEDs), current clinical experience with drug combinations and future treatment strategies in pharmacoresistant epilepsies. The majority of patients with newly diagnosed epilepsy can apparently be controlled with a single AED. At present, selection of AED combinations is mainly based on personal experience and on a few clinically documented studies. The aim of rational polytherapy is to improve the effectiveness to toxicity ratio: effectiveness should be supra-additive or at least additive and toxicity should be lower than additive. Everyday clinical practice suggests that in some pharmacotherapy-resistant patients, combination of three AEDs has a better effect than two drugs. Drug interactions may produce increases in desired metabolites or decreases in the formation of undesired metabolites. Resistance to pharmacotherapy occurs in a significant number of patients with chronic epilepsy; its pathogenesis and mechanism(s) of development are not fully understood.
  • 24 - Future research: an experimental perspective
    pp 441-457
    • By Rob A. Voskuyl, LACDR, Division of Pharmacology, Gorlaeus Laboratories, Leiden, The Netherlands; Epilepsy Institute of the Netherlands (SEIN), Achterweg, Heemstede, The Netherlands, Daniel M. Jonker, LACDR, Division of Pharmacology, Gorlaeus Laboratories, Leiden, The Netherlands; Epilepsy Institute of the Netherlands (SEIN), Achterweg, Heemstede, The Netherlands, Fernando H. Lopes da Silva, Epilepsy Institute of the Netherlands (SEIN), Achterweg, Heemstede, The Netherlands; Swammerdom Institute of Life Sciences (SILS), University of Amsterdam, The Netherlands
  • View abstract

    Summary

    This chapter discusses the factors influencing antiepileptic drug (AED) responses. It introduces the use of computer simulations based on mechanistic interaction models for designing efficient study protocols and data interpretation. The chapter deals with the assessment of the efficacy of combinations based on pharmacokinetic-pharmacodynamic (PK/PD) modeling of concentration-effect data. Development of new effective AEDs and therapeutic approaches ideally implies elucidation of the basic mechanisms of epileptogenesis and seizure generation and, thereby, identification of the appropriate targets. When evaluating the efficacy of drug combinations, the objectives are simple. Seizure semiology plays an important role in clinical diagnosis, but it is seldom used in pharmacologic studies. Determination of plasma concentrations is of utmost importance when evaluating drug combinations. Present knowledge of experimental animal models proposed for refractory epilepsy indicates that multiple factors contribute to its emergence. Simultaneously aiming drugs at the different targets could be a successful way to treat refractory epilepsy.
  • 25 - Future research: a clinical prospective
    pp 458-474
  • View abstract

    Summary

    Monotherapy implies the use of a single active entity and its advantages are recognized. The inappropriate application of drug combinations has been frequently coupled with inadequate recognition or understanding of epileptic syndromes. Pharmacovigilance is obligatory and must be improved for the study of drug interactions. Many studies suggest that multiple neurotransmitters and subtypes of their receptors are involved in the abnormal neuronal excitability that underlies some models of the epilepsies. Studies designed to test efficacy of drug combinations can be observational or experimental. For many antiepileptic drugs (AEDs), therapeutic serum level ranges are more or less well defined. In rational polypharmacy (RP), it is necessary to correlate serum levels with clinical efficacy since the combined drugs may be more active if the serum levels attained by each one in combination therapy are similar to those attained when the drug is used in monotherapy.

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