Opinion Leader Editorial - Epilepsy
(Publication Date 12 January 2005)

This Editorial has been written by specialist opinion leaders, Dr Charlotte Lawthom and Dr Philip Smith, The Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff and published in the latest issue of the serial publication, Drugs in Context.

Epilepsy is a common condition in the UK, with an incidence of approximately 80 cases per 100,000 population per year, and a prevalence of 5 - 10 cases per 1000. Yet, despite this high prevalence, it remains a stigmatising condition, with occupational and social disadvantages imposed on the individual. Epilepsy is difficult to diagnose, requiring a detailed history, and is complex to manage.

The primary aim of epilepsy therapy is seizure freedom. In this, the physician’s medical perspective tallies with the individual’s. Chief concerns for patients often include the regaining of a driving licence and potential lifting of occupational restrictions. However, ideal seizure management requires not only a medication script but also information and an accessible resource for support and questions.

There have been major advances in the understanding and management of epilepsy over the last 20 years, which have gone hand-in-hand with the proliferation of new anti-epileptic medications. Epilepsy services have also expanded with increased numbers of neurologists, epileptologists and epilepsy specialist nurses. Sadly, however, demand for epilepsy services continues to outstrip supply.

In managing newly diagnosed patients, it is worth noting that whilst up to 70% of patients are well controlled on their first drug (with the majority of these rendered seizure-free), the remaining 30% will still require further treatment. Of these, many will continue to have refractory epilepsy. There may be a number of concerns when deciding the next treatment option for these patients, which include licensing restrictions, potential drug interactions and safety and tolerability. In 2004, the National Institute for Clinical Excellence (NICE) published guidelines on the use of new anti-epileptic drugs in adults and children, and recommended their use generally as second-line medications.

The newer drugs (gabapentin, levetiracetam, lamotrigine, oxcarbazepine, pregabalin, tiagabine, topirimate, vigabatrin) were each initially licensed as add-on therapies for focal-onset seizures. Lamotrigine, oxcarbazepine and topirimate have since gained monotherapy licenses, whilst levetiracetam has recently gained a clause allowing withdrawal to monotherapy. Some newer medications (e.g. lamotrigine, topiramate) are also useful in primary generalised seizures. Several observational studies also suggest that levetiracetam may be effective in generalised epilepsies, although this is beyond its current licensed indication.

The new-generation anti-epileptic drugs have several theoretical advantages over the older drugs, including well-characterised mechanisms of action, improved tolerability and more predictable pharmacokinetics. Levetiracetam in particular has a unique cerebral binding site, which perhaps explains its apparent broad spectrum of action. The newer drugs are also generally more predictable than their predecessors when given in combination, having better defined mechanisms of action and less complex pharmacokinetics. Drugs such as gabapentin, levetiracetam and pregabalin are therefore easier to use than the older drugs, having no clinically significant drug interactions together with predictable renal excretion.

As with all new-generation agents, there is a relative lack of data in terms of patient-years and use in special patient groups. The risk of teratogenicity is crucially important when prescribing these newer drugs to women of childbearing potential. The UK Epilepsy and Pregnancy register has sufficient data from pregnancies after lamotrigine monotherapy to give us some assurance of its safety in pregnancy in contrast to valproate, though it will be years before equivalent data exist for the other newer drugs. Our experience with vigabatrin provides us with the most extraordinary example of delayed recognition of a serious complication: it took 8 years to identify that half of those prescribed vigabatrin developed permanent visual field defects. This reinforces the need for continued vigilance in following up patients on long-term anti-epileptic medications.

The future challenge of epilepsy care must be to achieve seizure freedom in our refractory patients. It is hoped that ongoing head-to-head clinical trials of currently available monotherapies will inform future practice. Ultimately, a complete understanding of the aetiology of epilepsy at both the cellular and molecular level, together with the emergence of pharmacogenomic data, may ultimately allow us to ‘best match’ treatments to individual patients. In the meantime, we must ensure that patients with epilepsy are fully informed about the potential advantages and pitfalls of the range of treatment options available, and always aim to prescribe for the individual. Given their position within the community, GPs are ideally placed to inform this decision-making and to respond to an individual’s changing circumstances. By developing effective specialist epilepsy services both within secondary and primary care, we will meet the growing demand for these services and also ultimately improve the care of our patients.

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