Early versus late antiepileptic drug withdrawal for people with epilepsy in remission

Sirven J, Sperling MR, Wingerchuk DM

Published Online:

April 18, 2012

There is not enough evidence to show the best time to withdraw antiepileptic drugs in adults with epilepsy who are free of seizures. More research is needed.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Antiepileptic drugs (AEDs) are used to prevent these seizures but have long term adverse effects. When in remission, it may be best to stop using the drugs but the right time to withdraw them is unclear. The review of trials found there is evidence to support waiting at least two years or more seizure free before discontinuing AEDs in children, especially if they had partial seizures or abnormal electroencephalogram (EEG). More research is needed.

Abstract (click to read)

Background:

This is an updated version of the original Cochrane review published in issue 3, 2001.

Antiepileptic drugs (AEDs) are used to prevent seizures but are associated with both short and long term adverse effects. When epilepsy is in remission, it may be in the individual's best interest to discontinue medication. However, the optimal timing of AED discontinuation is not known.

Objectives:

To quantify seizure relapse risk after early (less than two seizure free years) versus late (more than two seizure free years) AED withdrawal in adult and pediatric epilepsy patients.
To assess which variables modify the risk of seizure recurrence.

Search strategy:

We searched the Cochrane Epilepsy Group Specialised Register (October 2011), CENTRAL (Issue 4 of 4, The Cochrane Library Issue 2011), MEDLINE (1948 to September week 4, 2011), CINAHL (10 October 2011).

Selection criteria:

Randomized controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adults and children with epilepsy. Included studies compared an early versus late AED discontinuation.

Data collection and analysis:

Two authors independently extracted data and assessed trial quality. Relative risks (RR) with 95% confidence intervals (CI) were calculated for each trial. Summary RRs and 95% CIs for dichotomous data were calculated using a random-effects model. A test of statistical heterogeneity was conducted for each pooled relative risk calculation.

Main results:

Seven eligible controlled trials were included in the analysis representing 924 randomized children. There were no eligible trials evaluating seizure free adults. The pooled relative risk for seizure relapse in early versus late AED withdrawal was 1.32 (95% CI 1.02 to 1.70). On the basis of this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 10. Early discontinuation was associated with greater relapse rates in people with partial seizures (pooled RR is 1.52 (95% CI 0.95 to 2.41)) or an abnormal EEG (pooled RR 1.67 (95% CI 0.93 to 3.00)).

Authors' conclusions:

There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in children with generalized seizures. There is no evidence to guide the timing of withdrawal of AEDs in seizure free adults. Further blinded randomized controlled trials are needed to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

This record should be cited as:

Sirven J, Sperling MR, Wingerchuk DM. Early versus late antiepileptic drug withdrawal for people with epilepsy in remission. Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD001902. DOI: 10.1002/14651858.CD001902

Assessed as up to date:

October 10, 2011

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Primary Review Group:

Epilepsy Group

Health topics:

Neurology > Epilepsy > Withdrawing antiepileptic drugs

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Early versus late antiepileptic drug withdrawal for people with epilepsy in remission

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