Evidence-based Management of Epilepsy

Schachter, Steven C.

• Publisher: tfm Publishing Ltd
• Year: 2011
• Print ISBN:
  9781903378779
• eBook ISBN:
  9781908986726
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

The clinical management of patients with epilepsy and the associated medical literature are rapidly evolving. Evidence-based Management of Epilepsy differs from other epilepsy textbooks by focusing specifically on topics where the available evidence is sufficiently well developed to be synthesized into straightforward summaries of proven therapies. When evidence is missing or there is doubt, controversy or ambiguity, the distinguished authors offer treatment recommendations based on practice guidelines or consensus statements that span the gaps in evidence while pointing to those areas where further research is needed. The initial chapters cover critically important aspects of antiepileptic drugs (AEDs) and surgical treatment such as when to start and stop AEDs, how to monitor their effectiveness, special considerations in women who become pregnant, and when to consider surgery to alleviate seizures. The following chapters cover the therapy of seizures when they develop after traumatic brain injury or stroke, and the treatment of concomitant depression and anxiety in patients with epilepsy. The final chapters discuss emerging topics in epilepsy: the treatment of the postictal state, technologies to predict and detect seizures, strategies for closing the treatment gap and sudden unexpected death in epilepsy. The contributors are renowned experts in their fields who successfully and succinctly present state-of-the-art reviews based on the medical evidence designed to help the clinician be as best informed as possible in the care of patients with epilepsy.

Chapter 1

Starting, choosing, monitoring and stopping AEDs in epilepsy

Dieter Schmidt MD

Formerly Professor of Neurology, Free University of Berlin

Currently Head of Epilepsy Research Group, Berlin

Germany

Stefan Beyenburg MD

Neurologist, Senior Clinical Lecturer in Neurology

and Chef de Service, Department of Neurology

Centre Hospitalier de Luxembourg, Luxembourg

Introduction

Epilepsy is one of the most common neurological disorders and antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Although there is an abundance of short-term regulatory randomized controlled trials to assess the efficacy and safety of individual experimental AEDs prior to marketing, surprisingly, few trials have addressed the management of epilepsy with marketed AEDs in clinical practice. Good management of epilepsy requires to know when to start AEDs, what AED to choose, how to monitor AED treatment and when to stop AEDs. The present chapter provides a brief criticial overview on the strength of the evidence for making these major management decisions in epilepsy.

Starting AEDs

The rationale for starting treatment is to have a lower risk of seizure recurrence and better well-being compared to no treatment or deferred treatment. In this section we discuss the effects of AED treatment versus no treatment on time to recurrence, long-term seizure outcome, as well as well-being in patients with a single seizure and in those with several seizures prior to treatment.

Patients presenting with a single seizure

Among patients with a single seizure, only about 25% will have a recurrence within 2 years in the absence of factors that predict a high probability of recurrence ¹ (Ia/A). Risk factors for a higher seizure recurrence include primarily a known cause such as remote major head trauma or, in the case of generalized epilepsy, spike wave activity in the EEG ¹ (Ia/A). Even in patients with one or more risk factors, the recurrence rate at 2 years is not above 40%. A number of randomized controlled trials have compared AED treatment versus deferred treatment in patients presenting with a first seizure ^2-5 (Ib/A). Here we will discuss the largest trial ⁵ (Ib/A). For patients with a single seizure, the risk of relapse at 2 years of treatment was 32% for immediate treatment and 39% for deferred treatment. However, at 5 years, the risk was similar (42% for immediate and 51% for deferred treatment). The treatment effect between early and deterred treatment for 2-year remission was 12% at 2 years, 2% at 5 years and 1% at 8 years ⁵ (Ib/A). Regression analysis showed that the number of seizures before randomization, an abnormal EEG, and signs of a neurological or cognitive deficit increased the risk of seizure recurrence ⁶ (Ia/A). Low-risk patients were those with a single seizure, no neurological deficit, and a normal EEG. Medium-risk was seen in those with either 2-3 seizures or neurological signs or an abnormal EEG. All patients who had more seizures or more than one additional factor belonged to the high-risk group.

This is in agreement with randomized controlled trials showing that treatment reduces the risk of seizure recurrence on average by about 50% (range: 30-60%) and that those treated earlier have a better short-term seizure outcome versus those with no treatment or deferred treatment. However, the likelihood of being seizure-free at 3-5 years after a first or second seizure was similar whether treatment was started immediately or was deferred initially and started only if a further seizure occurred ⁵ (Ib/A). This is important evidence for two reasons: one, it shows for clinical practice that deferring treatment does not worsen prospects for becoming seizure-free, at least for those with low to medium risk for recurrence ⁶ (Ib/A); and, two, it provides clues for clinical science, that AEDs, even if they are actively blocking seizures, are not able to improve the course of the underlying disease, i.e. epilepsy. This finding is also in agreement with long-term studies of the natural history of treated epilepsy showing that early seizure remission may be followed by late relapse and thus does not guarantee permanent seizure freedom ⁷ (III/B).

Patients presenting with several recent seizures

Patients presenting with two or three seizures or even four or more seizures have a higher risk of seizure recurrence, which is further increased in those with neurological signs or an abnormal EEG ⁶ (Ib/A). High-risk patients, as defined above ⁶ (Ib/A), have a higher 5-year recurrence risk (73% vs. 50%) versus those with early treatment ⁶ (Ib/A). However, the risk following a second seizure has not been examined in a prospective population-based study of untreated patients ⁸ (Ib/A). The best available evidence for the risk of seizure recurrence comes from Hauser et al ⁹ (IIa/B) who prospectively followed 204 patients, 87% of which were treated with AEDs following their second seizure. The risk of a third seizure went up from 57% (95% CI, 45-70%) at 1 year and 73% (95% CI, 59-87%) at 4 years. The risk was higher in those with symptomatic epilepsy versus those with idiopathic or presumed symptomatic (cryptogenic) epilepsy. Shinnar et al ¹⁰ (Ia/A) reported similar findings in children followed up since their first seizure. A study reporting seizure recurrence in patients with several seizures who were randomized to treatment does not exist for ethical concerns, as it would deprive patients of needed proven treatment. The current recommendations on starting AEDs in patients with two or more seizures, particularly if they occurred within the last 6-12 months, are based on Hauser’s data ⁹ (IIa/B). Given this finding, starting AEDs is almost always justified in those with two or more seizures within the last 6-12 months provided the seizures are disabling, and cannot be controlled by avoiding precipitants. However, there are exceptions, such as patients with benign syndromes of childhood or adolescence or seizures that can easily be controlled by avoiding precipitants.

Choosing the right AED

Choosing the right AED for the individual patient is the result of a complex decision process that involves a risk-benefit assessment of the drug versus other suitable AEDs for the individual patient. In addition, other factors, which may play in the decision to prefer a drug over another one, include personal preference and ease of use based on past experience, a feeling of comfort, and last not least, cost. Unfortunately the vast majority of trials dealing with efficacy and safety of AEDs are designed for regulatory agencies which are primarily focused on evidence for short-term efficacy and safety of the drug versus placebo in the case of add-on treatment or low-dose controls in active monotherapy trials.

Choosing the right AED for patients with newly diagnosed epilepsy

In this section we will limit the discussion to a brief critical review of four influential benchmark trials that examined the long-term, comparative risk-benefit b...

Table of contents

• Cover Page
• Title Page
• Copyright Page
• Contents
• Foreword
• Contributors
• Acknowledgements
• Using Evidence-based Medicine
• Chapter 1: Starting, choosing, monitoring and stopping AEDs in epilepsy
• Chapter 2: Monitoring seizure frequency and severity in outpatients
• Chapter 3: When to consider epilepsy surgery, and what surgical procedure?
• Chapter 4: Optimizing decisions for treating women of child-bearing potential before and during pregnancy
• Chapter 5: Identification and management of depressive and anxiety disorders in epilepsy
• Chapter 6: Methods for evaluating and treating the postictal state
• Chapter 7: Strategies for closing the treatment gap of refractory epilepsy
• Chapter 8: Clinically relevant specifications for seizure prediction and detection systems
• Chapter 9: Reducing the risks of SUDEP: what do we know about risk factors and the prevention of SUDEP?
• Chapter 10: Behavioral therapies in the treatment of adults with epilepsy
• Chapter 11: Herbal remedies in epilepsy
• Chapter 12: Treatment of epilepsy and related comorbidities in patients with intellectual disabilities
• Chapter 13: Treatment of psychogenic non-epileptic seizures
• Index