Antiepileptic drug treatment after an unprovoked first seizure: A decision analysis

Abstract

Objective To compare the expected quality-adjusted life-years (QALYs) in adult patients undergoing immediate vs deferred antiepileptic drug (AED) treatment after a first unprovoked seizure.

Methods We constructed a simulated clinical trial (Markov decision model) to compare immediate vs deferred AED treatment after a first unprovoked seizure in adults. Three base cases were considered, representing patients with varying degrees of seizure recurrence risk and effect of seizures on quality of life (QOL). Cohort simulation was performed to determine which treatment strategy would maximize the patient's expected QALYs. Sensitivity analyses were guided by clinical data to define decision thresholds across plausible measurement ranges, including seizure recurrence rate, effect of seizure recurrence on QOL, and efficacy of AEDs.

Results For patients with a moderate risk of recurrent seizures (52.0% over 10 years after first seizure), immediate AED treatment maximized QALYs compared to deferred treatment. Sensitivity analyses showed that for the preferred choice to change to deferred AED treatment, key clinical measures needed to reach implausible values were 10-year seizure recurrence rate ≤38.0%, QOL reduction with recurrent seizures ≤0.06, and efficacy of AEDs on lowering seizure recurrence rate ≤16.3%.

Conclusion: Our model determined that immediate AED treatment is preferable to deferred treatment in adult first-seizure patients over a wide and clinically relevant range of variables. Furthermore, our analysis suggests that the 10-year seizure recurrence rate that justifies AED treatment (38.0%) is substantially lower than the 60% threshold used in the current definition of epilepsy.

Immediate vs delayed treatment of first unprovoked seizure: To treat, or not to treat?

Claire S. Jacobs and Jong Woo Lee

Neurology October 9, 2018 91:684-685; published ahead of print September 12, 2018

Deciding whether to treat or not to treat a first-ever seizure can be difficult, particularly when additional history provides no clear provoking mechanism and the critical ancillary tests such as MRI and EEG are uninformative. The practical clinical definition of epilepsy presented in the widely acknowledged International League Against Epilepsy (ILAE) official report is met under the following conditions: 2 unprovoked seizures >24 hours apart, 1 unprovoked seizure and seizure recurrence probability of >60% over the next 10 years, or diagnosis of an epilepsy syndrome.

The report explicitly states that treatment decisions are distinct from diagnosis (i.e., the presence of disease does not necessitate treatment and the absence of disease does not preclude treatment) and that treatment decisions should be tailored to the clinical scenario and individual patient. Despite this caveat, in practice, treatment decisions are frequently based on the ILAE's 60% threshold, resulting, for example, in deferred treatment in patients with first-ever unprovoked seizure and apparent probability of recurrence <60%, particularly in light of potential antiepileptic drug (AED) adverse side effects and no known disease-modifying properties of AEDs.

Because the reported seizure recurrence rates in patients with a first unprovoked seizure have ranged between 21% and 45% in the first 2 years,3 the practical result is that patients presenting with unprovoked first seizure and unrevealing workup are, almost by default, not treated with an AED.