An Introduction to Antiepileptic Drugs

Summary:  In recent years, the number of commercially available antiepileptic drugs (AEDs) has increased steadily. Although this may complicate management choices, it also offers welcome new options to individualize treatment more effectively. Because each of the available AEDs differs from others in many clinically relevant properties, opportunities to tailor drug treatment to the characteristics of the individual patient have never been greater. Properties that are especially important in drug selection in patients with epilepsy include spectrum of efficacy in different seizure types, adverse effects profile, pharmacokinetic properties, susceptibility to cause or be a target of clinically important drug–drug interactions, ease of use, and cost. Other factors that need to be considered in tailoring drug choice include availability of user‐friendly pediatric formulations, and potentially favorable effects on co‐morbid conditions. In fact, a number of AEDs are efficacious and widely prescribed in additional indications, particularly psychiatric disorders, migraine prophylaxis, and neuropathic pain. Recently, advances have been made in understanding the mechanisms of actions of AEDs at the molecular level. While a fully mechanistic approach to the clinical use of these agents is not yet feasible, knowledge of mechanisms of action offers useful clues in predicting their efficacy profile and spectrum of potential adverse effects.

[1]  D. Margineanu,et al.  Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? , 2003, Neuropharmacology.

[2]  J. Hallas,et al.  Antiepileptic drug utilization: a Danish prescription database analysis , 2001, Acta neurologica Scandinavica.

[3]  C. Vecht,et al.  Treating seizures in patients with brain tumors: Drug interactions between antiepileptic and chemotherapeutic agents. , 2003, Seminars in oncology.

[4]  鬼頭 正夫 Antiepileptic drugs-calcium current interaction in cultured human neuroblastoma cells , 1994 .

[5]  E. Beghi,et al.  The management of epilepsy in the 1990s. Acquisitions, uncertainties and priorities for future research. , 1995, Drugs.

[6]  P. Genton,et al.  Lamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy , 1998, Epilepsia.

[7]  E. Perucca,et al.  The new generation of antiepileptic drugs: advantages and disadvantages. , 1996, British journal of clinical pharmacology.

[8]  C. Vecht,et al.  Interactions between antiepileptic and chemotherapeutic drugs , 2003, The Lancet Neurology.

[9]  M. Brodie,et al.  Lamotrigine substitution study: evidence for synergism with sodium valproate? , 1997, Epilepsy Research.

[10]  Anticonvulsants , 1983, Brain and Development.

[11]  G. Avanzini,et al.  Antiepileptic Drugs as a Cause of Worsening Seizures , 1998, Epilepsia.

[12]  B. Meldrum Antiepileptic drugs potentiating GABA. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[13]  E. Perucca,et al.  Is There a Role for Therapeutic Drug Monitoring of New Anticonvulsants? , 2000, Clinical pharmacokinetics.

[14]  K. Fink,et al.  Inhibition of neuronal Ca2+ influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices , 2000, British journal of pharmacology.

[15]  B. Meldrum Update on the Mechanism of Action of Antiepileptic Drugs , 1996, Epilepsia.

[16]  E. Perucca Clinical pharmacology and therapeutic use of the new antiepileptic drugs , 2001, Fundamental & clinical pharmacology.

[17]  I. Leppik,et al.  The Place of Felbamate in the Treatment of Epilepsy , 1995 .

[18]  M. Brodie,et al.  Established antiepileptic drugs , 1997, Seizure.

[19]  M. Avoli,et al.  Neocortical Potassium Currents Are Enhanced by the Antiepileptic Drug Lamotrigine , 2002, Epilepsia.

[20]  D. Berry,et al.  Carbamazepine Toxicity with Lamotrigine: Pharmacokinetic or Pharmacodynamic Interaction? , 1998, Epilepsia.

[21]  E. Perucca,et al.  Clinical Significance of Pharmacokinetic Interactions Between Antiepileptic and Psychotropic Drugs , 2002, Epilepsia.

[22]  E. Perucca,et al.  Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs , 2003, The Lancet Neurology.

[23]  S. Shorvon,et al.  Assessing risk to benefit ratio in antiepileptic drug therapy , 2000, Epilepsy Research.

[24]  E. Perucca NICE guidance on newer drugs for epilepsy in adults , 2004, BMJ : British Medical Journal.

[25]  M. Eadie The Role of Therapeutic Drug Monitoring in Improving the Cost Effectiveness of Anticonvulsant Therapy , 1995, Clinical pharmacokinetics.

[26]  M. Vergnes,et al.  GABAB receptor antagonists: potential new anti-absence drugs. , 1992, Journal of neural transmission. Supplementum.

[27]  G. I. Rozova,et al.  Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites. , 1992, British journal of clinical pharmacology.

[28]  R. Kälviäinen,et al.  Visual Field Defects with Vigabatrin , 2001, CNS drugs.

[29]  G. van Luijtelaar,et al.  Opposite effects of T- and L-type Ca(2+) channels blockers in generalized absence epilepsy. , 2000, European journal of pharmacology.

[30]  M. Pappagallo Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. , 2003, Clinical therapeutics.

[31]  E. Perucca,et al.  Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs , 2003, The Lancet Neurology.

[32]  G. Mathern,et al.  Epilepsia , 1991, NEURO FUNDAMENTAL.

[33]  R. Davis,et al.  Topiramate. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of epilepsy. , 1997, Drugs.

[34]  K. Goa,et al.  Oxcarbazepine: an update of its efficacy in the management of epilepsy. , 2001, CNS drugs.

[35]  E. Perucca Overtreatment in epilepsy: adverse consequences and mechanisms , 2002, Epilepsy Research.

[36]  M. Brodie,et al.  Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy , 1999, Epilepsy Research.

[37]  K. Nocka,et al.  The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Morrell,et al.  Management issues for women with epilepsy , 1998, Neurology.

[39]  R. Post,et al.  Potential Mechanisms of Action of Lamotrigine in the Treatment of Bipolar Disorders , 2003, Journal of clinical psychopharmacology.

[40]  Rong-Chi Chen,et al.  Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytoin and possible therapeutic implications. , 1997, Molecular pharmacology.

[41]  F. Besag Approaches to Reducing the Incidence of Lamotrigine-Induced Rash , 2000 .

[42]  Meldrum Bs Antiepileptic drugs potentiating GABA. , 1999 .

[43]  E. Perucca,et al.  Sodium Valproate and Valpromide: Differential Interactions with Carbamazepine in Epileptic Patients , 1986, Epilepsia.

[44]  S. Shorvon,et al.  Antiepileptic drugs: coprescription of proconvulsant drugs and oral contraceptives: a national study of antiepileptic drug prescribing practice , 2002, Journal of neurology, neurosurgery, and psychiatry.

[45]  R. Post,et al.  A speculative model of affective illness cyclicity based on patterns of drug tolerance observed in amygdala-kindled seizures , 1996, Molecular Neurobiology.

[46]  R. Chaponis,et al.  An Evaluation of Antiepileptic Drug Therapy In Nursing Facilities , 1998, Journal of the American Geriatrics Society.

[47]  S. Shorvon,et al.  Harnessing the Clinical Potential of Antiepileptic Drug Therapy , 2001, CNS drugs.

[48]  Alasdair Breckenridge,et al.  Meyler's Side Effects of Drugs , 1976 .

[49]  T. Tomson,et al.  Navigating toward Fetal and Maternal Health: The Challenge of Treating Epilepsy in Pregnancy , 2004, Epilepsia.

[50]  E. Perucca,et al.  The Efficacy of Valproate‐Lamotrigine Comedication in Refractory Complex Partial Seizures: Evidence for a Pharmacodynamic Interaction , 1999, Epilepsia.

[51]  A. Evins,et al.  Efficacy of newer anticonvulsant medications in bipolar spectrum mood disorders. , 2003, The Journal of clinical psychiatry.

[52]  E. Perucca Current Trends in Antiepileptic Drug Therapy , 2003, Epilepsia.

[53]  A. Richens Clinical Pharmacokinetics of Phenytoin , 1979, Clinical pharmacokinetics.