Clinical Evidence Handbook

A Publication of BMJ Publishing Group

Epilepsy



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Am Fam Physician. 2009 Nov 15;80(10):1151-1152.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See CME Quiz on page 1063.

About 3 percent of persons are diagnosed with epilepsy during their lifetime, but about 70 percent of persons with epilepsy eventually go into remission.

After a first seizure, antiepileptic drugs may delay or prevent subsequent seizures, but they can cause adverse effects, and their long-term benefit is unknown. Antiepileptic drug treatment after a single seizure does not reduce the risk of drug-resistant epilepsy in the long term.

Carbamazepine, phenobarbital, phenytoin, lamotrigine, sodium valproate, and topiramate are widely considered effective in controlling seizures in newly diagnosed partial or generalized (tonic-clonic) epilepsy, but we found no randomized controlled trials comparing the drugs with placebo. A placebo-controlled trial would now be considered unethical.

  • Systematic reviews found no reliable evidence on which to base a choice among anti-epileptic drugs.

  • Adding second-line drugs to usual treatment reduces seizure frequency in persons with drug-resistant partial epilepsy, but increases adverse effects such as dizziness and somnolence. We do not know if any one antiepileptic drug is more likely to reduce seizures compared with others.

In persons who have been seizure-free for at least two years while on treatment, almost 60 percent of those who withdraw from antiepileptic treatment remain seizure-free, compared with almost 80 percent of persons who continue treatment.

Educational programs may reduce seizure frequency and improve psychosocial functioning in persons with epilepsy, but we do not know whether other behavioral or psychological treatments are beneficial.

There is consensus that temporal lobectomy or amygdalohippocampectomy can improve seizure control and quality of life in persons with drug-resistant temporal lobe epilepsy, but the procedures can cause neurologic adverse effects.

High-level vagus nerve stimulation may reduce seizure frequency in persons with drug-resistant partial seizures, but it may cause hoarseness and dyspnea, and long-term effects are unknown. We do not know whether different stimulation cycles more effectively reduce seizure frequency or increase the proportion of responders.

We do not know whether hemispherectomy improves seizure control in persons with drug-resistant epilepsy.

Caution: Vigabatrin, which may be used as second-line treatment, causes concentric visual field abnormalities, which are probably irreversible in about 40 percent of persons.

Clinical Questions

What are the benefits and risks of starting antiepileptic drug treatment after a single seizure?

Trade-off between benefits and harms

Antiepileptic drugs

What are the effects of monotherapy in newly diagnosed partial epilepsy?

Likely to be beneficial

Carbamazepine*

Lamotrigine*

Phenobarbital*

Phenytoin*

Sodium valproate*

Topiramate*

What are the effects of monotherapy in newly diagnosed generalized epilepsy (tonic-clonic type)?

Likely to be beneficial

Carbamazepine*

Lamotrigine*

Phenobarbital*

Phenytoin*

Sodium valproate*

Topiramate*

What are the effects of additional treatments in persons with drug-resistant partial epilepsy?

Beneficial

Addition of second-line drugs (allopurinol, esclicarbazepine, gabapentin, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide)

What is the risk of relapse in persons in remission when withdrawing antiepileptic drugs in partial or generalized epilepsy?

Trade-off between benefits and harms

Antiepileptic drug withdrawal

What are the effects of behavioral and psychological treatments in persons with partial or generalized epilepsy?

Likely to be beneficial

Educational programs

Unknown effectiveness

Biofeedback

Cognitive behavior therapy

Family counseling

Relaxation plus behavioral modification therapy

Relaxation therapy

Yoga

What are the effects of surgery in persons with drug-resistant temporal lobe epilepsy?

Likely to be beneficial

Amygdalohippocampectomy*

Temporal lobectomy*

Vagus nerve stimulation as adjunctive therapy for drug-resistant partial seizures

Unknown effectiveness

Lesionectomy

What are the effects of surgery in persons with drug-resistant generalized epilepsy?

Unknown effectiveness

Hemispherectomy


*— Categorization based on consensus.

Clinical Questions

View Table

Clinical Questions

What are the benefits and risks of starting antiepileptic drug treatment after a single seizure?

Trade-off between benefits and harms

Antiepileptic drugs

What are the effects of monotherapy in newly diagnosed partial epilepsy?

Likely to be beneficial

Carbamazepine*

Lamotrigine*

Phenobarbital*

Phenytoin*

Sodium valproate*

Topiramate*

What are the effects of monotherapy in newly diagnosed generalized epilepsy (tonic-clonic type)?

Likely to be beneficial

Carbamazepine*

Lamotrigine*

Phenobarbital*

Phenytoin*

Sodium valproate*

Topiramate*

What are the effects of additional treatments in persons with drug-resistant partial epilepsy?

Beneficial

Addition of second-line drugs (allopurinol, esclicarbazepine, gabapentin, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide)

What is the risk of relapse in persons in remission when withdrawing antiepileptic drugs in partial or generalized epilepsy?

Trade-off between benefits and harms

Antiepileptic drug withdrawal

What are the effects of behavioral and psychological treatments in persons with partial or generalized epilepsy?

Likely to be beneficial

Educational programs

Unknown effectiveness

Biofeedback

Cognitive behavior therapy

Family counseling

Relaxation plus behavioral modification therapy

Relaxation therapy

Yoga

What are the effects of surgery in persons with drug-resistant temporal lobe epilepsy?

Likely to be beneficial

Amygdalohippocampectomy*

Temporal lobectomy*

Vagus nerve stimulation as adjunctive therapy for drug-resistant partial seizures

Unknown effectiveness

Lesionectomy

What are the effects of surgery in persons with drug-resistant generalized epilepsy?

Unknown effectiveness

Hemispherectomy


*— Categorization based on consensus.

Definition

Epilepsy is a group of disorders rather than a single disorder. Seizures can be classified as partial or focal (categorized as simple partial, complex partial, and secondary generalized tonic-clonic seizures) or as generalized (categorized as generalized tonic-clonic, absence, myoclonic, tonic, and atonic seizures). Temporal lobe epilepsy is a form of partial or focal epilepsy. Persons are considered to have epilepsy if they have had two or more unprovoked seizures.

Incidence and Prevalence

Epilepsy is common, with an estimated prevalence in resource-rich countries of five to 10 out of 1,000 persons, and an annual incidence of 50 out of 100,000 persons. About 3 percent of persons will be diagnosed with epilepsy at some time in their lives.

Etiology

Epilepsy is a symptom rather than a disease, and it may be caused by various disorders involving the brain. The causes and risk factors include birth or neonatal injuries, congenital or metabolic disorders, head injuries, tumors, infections of the brain or meninges, genetic defects, degenerative disease of the brain, cerebrovascular disease, and demyelinating disease. Epilepsy can be classified by cause. Idiopathic generalized epilepsies (e.g., juvenile myoclonic epilepsy, childhood absence epilepsy) are largely genetic. Symptomatic epilepsies result from a known cerebral abnormality. For example, temporal lobe epilepsy may result from a congenital defect, mesial temporal sclerosis, or a tumor. Cryptogenic epilepsies are those that cannot be classified as idiopathic or symptomatic.

Prognosis

About 60 percent of untreated persons have no further seizures during the two years after their first seizure. Prognosis is good for most persons with epilepsy. About 70 percent go into remission, defined as being seizure-free for five years on or off treatment. This leaves 20 to 30 percent who develop chronic epilepsy, which is often treated with multiple antiepileptic drugs.

Author disclosure: Anthony Marson has been paid by Johnson & Johnson, Janssen-Cilag, Sanofi Aventis, and UCB for speaking at meetings, and by Glaxo Wellcome and UCB for attending conferences. Sridharan Ramaratnam has received hospitality from Sun Pharmaceutical (India), Novartis (India), and Sanofi Aventis for attending conferences; is involved in ongoing clinical trials for UCB, Pfizer, and Johnson & Johnson; and is an author of systematic reviews referenced in this review.

Adapted with permission from Marson A, Maguire M, Ramaratnam S. Epilepsy. Clin Evid Handbook. June 2009: 421–423. Please visit http://www.clinicalevidence.bmj.com for full text and references.

editor's note: Esclicarbazepine, losigamone, and retigabine are not available in the United States.

 

search date: April 2007

This is one in a series of chapters excerpted from the Clinical Evidence Handbook, published by the BMJ Publishing Group, London, U.K. The medical information contained herein is the most accurate available at the date of publication. More updated and comprehensive information on this topic may be available in future print editions of the Clinical Evidence Handbook, as well as online at http://www.clinicalevidence.bmj.com (subscription required). Those who receive a complimentary print copy of the Clinical Evidence Handbook from United Health Foundation can gain complimentary online access by registering on the Web site using the ISBN number of their book.



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