Elsevier

The Lancet Neurology

Volume 3, Issue 10, October 2004, Pages 618-621
The Lancet Neurology

Rapid Review
Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines

https://doi.org/10.1016/S1474-4422(04)00882-8Get rights and content

Summary

Background

Until the early 1990s six major compounds (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid) were available for the treatment of epilepsy. However, these drugs have pharmacokinetic limitations, teratogenic potential, and a negative effect on cognitive functions that impairs the quality of patients' lives and limits the use of these drugs in some patients. In addition, 20–30% of patients are refractory to these drugs.

Recent developments

The development of ten new antiepileptic drugs (vigabatrin, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin) has expanded treatment options. The newer drugs may be better tolerated, have fewer drug interactions, and seem to affect cognitive functions to a lesser extent than old drugs. Guidelines on the use of new antiepileptic drugs have been developed in the USA and in the UK. Both guidelines offer a clear picture of the efficacy, safety, and tolerability of the new antiepileptic drugs and agree on their use as add-on treatment in patients who do not respond to conventional drugs. The guidelines differ in the type and strength of recommendations. Whereas the US guidelines recommend treatment in newly diagnosed epilepsy with a standard drug or a new drug depending on the individual patient's characteristics, the UK guidelines recommend that a new antiepileptic drug should be considered only if there is no benefit from an old antiepileptic drug, an old drug is contraindicated, there is a previous negative experience with the same drug, or the patient is a woman of childbearing potential.

Where next

The limited amount of information on the new antiepileptic drugs may explain the discrepancies among the two guidelines and between these and other recommendations. Comparative, pragmatic, long-term and open trials should be done to show long-term efficacy and comparative features of the new antiepileptic drugs, and to better assess the effect on quality-of-life, cost-effectiveness, tolerability, and teratogenic potential. In addition, the conflicts should be resolved between the needs of the regulatory bodies and those of the treating physicians. Finally, there is a need for trial designs to be standardised.

Section snippets

US and UK guidelines

Guidelines for the pharmacological treatment of epilepsy and, more specifically, for the use of the newer antiepileptic drugs, have been devised recently in the USA3, 4 and in the UK.5, 6 In the USA, the Therapeutic and Technology Assessment Subcommittee and the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society did a literature search for relevant articles on the efficacy, tolerability, and safety of seven new antiepileptic drugs (gabapentin,

Newly diagnosed partial epilepsy

The new antiepileptic drugs seemed to be similar to the older compounds in efficacy, but superior in tolerability. Overall, evidence is insufficient to assess the effect of old and new drugs on quality of life. There is insufficient evidence to suggest differences in efficacy among newer antiepileptic drugs. On this basis, the US panel recommended patients with newly diagnosed (previously untreated) epilepsy to be treated with an older drug or with a new drug among lamotrigine, gabapentin,

Children and patients with learning disabilities and intellectual deficits

Although these patients have been shown to benefit from new antiepileptic drugs to the same extent as adults with epilepsy, and beneficial effects were obtained on behavioural symptoms with lamotrigine and gabapentin, safety and tolerability concerns have been raised by the UK panel. In addition, there is no strong or consistent evidence of a difference between drugs in their effects on cognitive functions. However, none of the guidelines mentioned differential modes of treatment in these

Discrepancies between the US and UK guidelines and other recommendations

The UK guidelines seem to contrast with the Scottish Intercollegiate Network Guidelines (SIGN),11 which expand on the use of drugs in a synthesised management of epilepsy and suggest using lamotrigine and oxcarbazepine as first-line treatments for partial and symptomatic generalised seizures and lamotrigine as first-line treatment for idiopathic generalised seizures. However, a revised version of the UK guidelines is forthcoming, having a format comparable to the SIGN guidelines. The US

Conclusions

The US and the UK guidelines on the use of the new antiepileptic drugs for the treatment of epilepsy are both useful instruments for practising physicians (epileptologists, neurologists, child neurologists, neurosurgeons and—to some extent—family practitioners) because they are evidence-based, fairly comprehensive, and up-to-date. However, the guidelines diverge on the management of newly diagnosed epilepsy. As compared with the US guidelines, which links the choice of a new antiepileptic drug

References (12)

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