Cochrane for Clinicians
Putting Evidence into Practice
When to Discontinue Antiepileptic Drug Therapy for Patients in Remission
Am Fam Physician. 2016 Jun 1;93(11):914-915.
Author disclosure: No relevant financial affiliations.
In patients with a history of epilepsy, how long must one be seizure-free before stopping antiepileptic drug therapy?
Children with epilepsy should be seizure-free for at least two years before stopping antiepileptic drug therapy, especially those who have partial seizures or a history of abnormal electroencephalography (EEG) results. Evidence is insufficient to guide this decision for children with generalized seizures, and there is no evidence with which to answer this question for adults. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Patients sometimes present to their family physician requesting discontinuation of their seizure medication, yet doing so prematurely can be harmful. A detailed history is important to establish whether seizures were focal (partial) or generalized (involving bilateral hemispheres of the brain), and whether consciousness was impaired. Attempts should be made to retrieve EEG or imaging study results. Furthermore, some patients may have had nonepileptic (psychogenic) seizures or seizures provoked by a resolved stimulus (e.g., fever, alcohol or drug withdrawal).1
The authors of this Cochrane review assessed the risk of discontinuing antiepileptic drug therapy in children and adults with true epilepsy. They defined epilepsy as two or more unprovoked seizures at least 24 hours apart, one seizure with very high risk of recurrence because of an underlying condition, or a diagnosis of epilepsy syndrome. The authors searched for randomized controlled trials comparing patients with epilepsy who underwent early (less than two continuous years seizure-free) vs. late (two or more years seizure-free) withdrawal of antiepileptic drugs. Neonates were excluded. Five trials with a total of 924 children were ultimately included in the meta-analysis; the most recent trial was published in 2000.
Four of the trials were conducted in affluent European countries, and one took place in Ethiopia. Blinding of groups was not considered feasible or ethical. The studies lasted from six months to seven years and included an initial taper of antiepileptic drugs over one month to one year. Overall, late withdrawal of antiepileptic drugs decreased the risk of seizure relapse (34% vs. 46%; P < .001; number needed to treat = 8) compared with early withdrawal.
The studies included heterogeneous patient populations with different seizure types who were receiving different medications and undergoing various taper protocols. Abnormal EEG findings increased the risk of relapse (pooled relative risk = 1.44; 95% confidence interval, 1.13 to 1.83; P = .003). Other factors that increased the risk of seizures included diagnosis of seizure disorder before two years or after 10 years of age, history of status epilepticus, an intellectual disability (IQ lower than 70), and a high seizure frequency before and during treatment. Only one trial included patients with generalized seizures; no conclusion could be reached regarding risk of relapse.
In 1994, the American Academy of Neurology published guidelines recommending discontinuation of antiepileptic drug therapy if the following criteria are met: seizure-free for two to five years, only one type of epilepsy, normal EEG findings, and normal neurologic examination findings.2 The Italian League Against Epilepsy recommends a minimum of two years seizure-free and tapering of antiepileptic drugs over at least six months.3 A 2010 review of randomized and nonrandomized trials addressed risk factors affecting the prognosis after discontinuing medication.4 The author concluded that sudden death and development of a treatment-refractory, resistant form of epilepsy are rare and should not be emphasized in the shared decision-making process.
Strozzi I, Nolan SJ, Sperling MR, Wingerchuk DM, Sirven J. Early versus late antiepileptic drug withdrawal for people with epilepsy in remission. Cochrane Database Syst Rev. 2015;(2):CD001902.
The practice recommendations in this activity are available at http://summaries.cochrane.org/CD001902.
REFERENCESshow all references
1. Wilden JA, Cohen-Gadol AA. Evaluation of first nonfebrile seizures. Am Fam Physician. 2012;86(4):334–340....
2. American Academy of Neurology Quality Standards Subcommittee. Practice parameter: a guideline for discontinuing antiepileptic drugs in seizure-free patients—summary statement. Neurology. 1996;47(2):600–602.
3. Beghi E, Giussani G, Grosso S, et al. Withdrawal of antiepileptic drugs: guidelines of the Italian League Against Epilepsy. Epilepsia. 2013;54(suppl 7):2–12.
4. Hixson JD. Stopping antiepileptic drugs: when and why? Curr Treat Options Neurol. 2010;12(5):434–442.
These are summaries of reviews from the Cochrane Library.
This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.
A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.
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