Rapid versus slow withdrawal of antiepileptic drugs.

BACKGROUND: The ideal objective of treating a person with epilepsy is to induce remission by usage of antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term side effects. Hence when a person with epilepsy is in remission (free of seizures for some time) it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review proposes to examine the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on recurrence of seizure. This review also examines the effect of variables such as age of seizure onset, seizure types, presence of neurological deficits, mental subnormality, aetiology of epilepsy, type of AED, EEG findings or duration of seizure freedom on the risk of recurrence of seizures with the two tapering regimens.

OBJECTIVES: (1) To quantify risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period or more than three months) discontinuation of antiepileptic drugs in adults with epilepsy who are in remission. (2) To quantify the risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period of more than three months) discontinuation of antiepileptic drugs in children with epilepsy who are in remission. (3) To attempt to assess which variables modify the risk of seizure recurrence.

SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2004) and cross-references from identified studies. No language restrictions were imposed.

SELECTION CRITERIA: Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow manner after varying periods of seizure control in patients with epilepsy.

DATA COLLECTION AND ANALYSIS: Both review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure relapse (i.e. the percentage of patients experiencing seizure recurrence after withdrawal of AED); time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure such as injuries, fractures, aspiration pneumonia; and quality of life (if assessed by validated scale).

MAIN RESULTS: One trial with weak methodology involving 149 children was included with a mean age of seizure onset of four years, mean age of 11 years at the time of starting the taper. The rapid taper group (six weeks) recruited 81 participants and the slow taper group (nine months) included 68 participants, out of whom 11 and 5 were lost to follow up even before the taper began respectively. The number of participants who were seizure free in the rapid and slow taper groups were 40 and 44 respectively at the end of one year follow up (OR 0.53, 95% CI 0.27 to 1.03); 30 and 29 respectively at the end of two years, (OR 0.79, 95% CI 0.41 to 1.53); 24 and 14 respectively at the end of three years (OR 1.62, 95% CI 0.76 to 3.46); 18 and 8 respectively at the end of four years (OR 2.14, 95% CI 0.87 to 5.3); 10 and 6 respectively at the end of five years (OR 1.46, 95% CI 0.5 to 4.23).

AUTHORS' CONCLUSIONS: In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.