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Modeling favors immediate AED after unprovoked first seizure

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Findings shift discussion toward immediate treatment

The conclusion of this decision analysis by Bao and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to authors of an accompanying editorial.

The decision analysis is based on a reasonable though not comprehensive set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, said in the editorial.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, quality-adjusted life years (QALYs) can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, authors suggested. “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,” they wrote.

Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD , are with department of neurology, Brigham and Women’s Hospital, Boston. Their editorial appeared in Neurology . Dr. Jacobs reported being partially supported by NIH/National Institute of Neurological Disorders and Stroke and is an inventor on patents related to synthesis and use of DNA-binding small molecules targeted to transcription factor–binding sites. Dr. Lee reported that he has received prior NIH funding, has served on the scientific advisory board of Lundbeck, has done contract work for SleepMed/DigiTrace and Advance Medical.



Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, the model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patients with a single unprovoked seizure, according to their report in Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, of the department of neurology, Massachusetts General Hospital, Boston, and his coauthors in their report.

“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,” they said in a discussion of their study results.

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy – immediate or delayed AED – would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first base case was a 30-year-old man with no other risk factors for recurrent seizure, other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation indeed favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they wrote.

The study was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke. Dr. Westover and his coauthors had no relevant disclosures to report.

SOURCE: Bao EL et al. Neurology. 2018 Sep 12. pii: 10.1212/WNL.0000000000006319.

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