Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy
Geerts AT, Niermeijer JMF, Peters ACB, Arts WFM, Brouwer OF, et al.;
Commented by , 21 Sep 2005
Background
There is limited data on long-term outcome after early withdrawal of antiepileptic drug (AED) therapy in seizure-free patients (ref. 1).
Aim
To assess seizure recurrence rates at 4 years after early withdrawal of AEDs in children with epilepsy.
Methods
- Children aged 1 month to 16 years with > or = 2 unprovoked seizures or one status epilepticus who became seizure-free within 2 months after starting treatment and remained so for 6 months were randomized to medication withdrawal at that time (6-month group) or after another 6 months of treatment (12-month group).
- Results at 2 years after randomization were reported previously (ref. 2). In this study, follow-up was extended to 4 years
- Excellent outcome was defined as seizure freedom without medication during the last 2 years of follow-up.
Results
Four years after randomization, 55% of 161 children had a recurrence (59% in the 6-month group and 51% in the 12-month group)
The 6-month group had relatively more late recurrences, but the difference was not significant
Seventy-eight (51%) of 154 children (cohort with complete data set at 4 years) had an excellent outcome, without differences between groups
Prognostic factors for good outcome were seizures beginning before age 6 years, absence seizures, idiopathic epilepsy, no postictal signs and a normal EEG.
Professor Perucca's comments
In this study, AEDs were discontinued early (after as little as 6-months of seizure freedom in one group), in contrast with the standard practice of waiting for 1 to 2 years before attempting withdrawal of medication (ref. 1).
The recurrence rates at 4 years (55%) in this study is higher than that found in other studies when AED withdrawal was started after longer seizure freedom periods (ref. 1; ref. 3).
Although this may reflect a selection bias (a longer seizure freedom on medication may pre-select patients with a good prognosis), the inclusion of patients achieving seizure freedom within 2 months of starting treatment may also pre-select patients with good prognosis.
Until more information is available, I would endorse the authors' statement that "early medication withdrawal is not recommended in children with a rapid response to medication".
These data, in any case, confirm that general notion that outcome following AED discontinuation in seizure-free children is favourable in a large proportion of cases. The positive prognostic factors in this study are similar to those identified in earlier investigations (ref. 4; ref. 5; ref. 6; ref. 7; ref. 8; ref. 3).
AEDs may cause significant adverse effects in children, particularly on cognition and behaviour, and withdrawal of AED in seizure-free patients should be always considered (ref. 9; ref. 10).
The benefit/risk ratio of treatment withdrawal is generally higher in children than in adults, because may childhood epilepsies undergo spontaneous remission. Moreover, the psycho-social consequences of seizure recurrence are probably less in children than in adults.
Obviously, recurrence risk must be determined for each individual case, and the implications discussed with the child and his/her parents (ref. 10).
An important question is whether recurrent seizures may put the child at risk for developing seizures that are more difficult to control. We have no good studies to answer this question conclusively, but there is no hard evidence that AED withdrawal may cause emergence of intractable seizures.
In this study, most children whose seizures relapsed regained control after re-starting medication. About one quarter had seizure recurrences after re-starting medication, but it is unclear whether or not control was ultimately re-achieved.
In fact, a recent population-based study from Nova Scotia concluded that only about 1% of children who became seizure-free and discontinued AEDs had recurrent seizures that could not be controlled again with medication (ref. 11).
Although all studies conducted so far had limited duration of follow-up, and could not exclude the possibility of intractable seizures re-emerging after years of remission (ref. 12), most of the available data seem to be reassuring.
References
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