Earlier treatment better than later in unprovoked first seizure


By Nicola Garrett

21 Sep 2018

In adults with an unprovoked first seizure the use of immediate antiepileptic therapy is preferable to deferred treatment, a novel decision analysis model concludes.

Writing in Neurology, researchers from Harvard Medical School said current guidelines from the International League Against Epilepsy (ILEA) recommended making a diagnosis of epilepsy if patients met one of the following criteria: at least 2 unprovoked seizures occurring >24 hours apart, 1 unprovoked seizure and a probability of further seizures over the next 10 years ≥60%, or diagnosis of an epilepsy syndrome.

However, they said the one-size fits-all threshold of 60% for epilepsy diagnosis and antiepileptic drug (AED) treatment overlooked the need to personalise recommendations on the basis of a patient’s specific comorbidities and seizure burden and the effects of the decision on the patient’s quality of life (QOL).

“An important unresolved question is, which patients with a first unprovoked seizure can expect a net benefit from immediate AED treatment, and which patients should begin treatment only after experiencing further seizures?,” they wrote.

They therefore set out to answer the question by developing a decision model based on a set of clinical parameters to simulate three base cases representing patients with a first seizure across a spectrum of seizure risk, effect of recurrence on quality of life and the risk of AED side effects.

Base case 1 represented a typical patient with a first seizure with no particular risk factors for recurrent seizure other than having had a first seizure. Base case 2 represented a scenario in which immediate AED therapy would be strongly recommended as a result of a high risk of recurrent seizures and base case 3 involved a scenario in which current definitions would operationally classify as epilepsy, but immediate AED therapy would be intuitively discouraged due to a high risk of AED adverse effects and a minimal expected increase in QOL.  

For base case 2 the model favoured immediate AED therapy, which the authors said was consistent with expectations. For base case 3 the model favoured deferred AED treatment over immediate treatment, albeit the authors noted, by a small margin.

But for base case 1, which represented a typical patient with a first seizure with no particular risk factors for recurrent seizure other than having had a first seizure, the model favoured immediate AED therapy, despite the patient not meeting  meet the current ILAE definition of epilepsy.

According to the authors this finding suggested the current ILAE definition of epilepsy, which relies on baseline recurrent seizure risk alone to define epilepsy after a first unprovoked seizure, was too simplistic for deciding whether to start or withhold AED treatment.

They added that their decision analysis showed that immediate AED treatment might provide a net benefit to patients after a first unprovoked seizure even if they have relatively low risk for recurrent seizure (base case 1) and that a high baseline risk for recurrent seizures does not by itself always favours immediate AED treatment (base case 3).

“Therefore, a more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment” the study authors said.

An accompanying editorial cautioned that the decision analysis must be viewed in the context that it is dependent on its parameters. It had also not assessed the economic costs of medications or patient preference.

Nevertheless, the overarching conclusion of the decision analysis was “likely correct, namely that early treatment may be favourable over a larger number of clinical situations,” the editorialist wrote.

“At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease.”

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