Stopping Seizure Meds Before Hospital Discharge Appears Safe in Most Newborns

By Lorraine L. Janeczko

June 02, 2021

NEW YORK (Reuters Health) - For most newborns with acute symptomatic seizures, doctors can safely stop antiseizure medications before hospital discharge, without worse neurodevelopmental outcomes or increased risk of epilepsy, a new study suggests.

"For newborns with acute symptomatic seizures due to brain injury, we found that it is safe to stop all antiseizure medications after the seizures resolve on electroencephalogram (EEG) for 24 hours and before they go home from the hospital," said Dr. Hannah C. Glass of the University of California, San Francisco.

"The findings are important because antiseizure medications such as phenobarbital can be harmful when used for long durations," she told Reuters Health by email. "We want to minimize harm by limiting treatment duration to the shortest time that is also safe."

The research team compared the effectiveness of discontinuing vis-a-vis maintaining antiseizure therapy (phenobarbital monotherapy, levetiracetam monotherapy, or polytherapy) after discharge from neonatal-seizure hospital admission. The 303 neonates with acute symptomatic seizures who were included in the study were born over about three years and treated at nine U.S. Neonatal Seizure Registry centers.

At 24 months, the researchers measured functional neurodevelopment with the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS). Outcome risks adjusted for propensity to receive antiseizure medication at discharge included seizure cause, gestational age, worst electroencephalogram (EEG) background, days of EEG seizures, therapeutic hypothermia, and discharge examination.

Overall, 64% of children had antiseizure medication maintained after discharge, with a median duration of therapy of four months, the researchers report in JAMA Neurology.

Of the 270 children who were evaluated at 24 months, the 101 (37%) whose ASMs were discontinued and the 169 (63%) whose ASMs were maintained had similar WIDEA-FS scores (median 165 vs. 161, respectively; P=0.09), with a non-significant propensity-adjusted average difference of four points.

The epilepsy risk in both groups was also similar (11% for the discontinuation group vs. 14% of the maintenance group; P=0.49), with a propensity-adjusted odds ratio of 1.5 (P=0.32).

Senior author Dr. Renee A. Shellhaas of C. S. Mott Children's Hospital in Ann Arbor, Michigan, explained that the findings support the results of smaller studies and provide "the first time that we have data from multiple centers with rigorous diagnosis and follow-up for neonates with acute symptomatic seizures caused by a range of etiologies."

"Parents told us very clearly that medication side effects and treatment duration were key concerns, and that it is critical to look at neurodevelopmental outcomes and risk of post-neonatal epilepsy for survivors of neonatal seizures," she added.

Several clinicians who were not involved in the study agreed with its recommendations.

Drs. Eric T. Payne of the University of Calgary, in Canada, and Elaine C. Wirrell of Mayo Clinic in Rochester, Minnesota, note in a linked editorial, "In the field of epilepsy treatment, we are often caught between the proverbial rock and hard place: our seizure medications can cause harm but so can seizures. Glass and colleagues provide important and robust evidence to address this contentious issue."

Dr. Amy R. Brooks-Kayal, chair of the department of neurology at the University of California, Davis, Medical Center, in Sacramento, told Reuters Health by email, "Since phenobarbital is still the most commonly used ASM for neonatal seizures, and it has potential neurotoxic effects, continuing it longer than is necessary could cause adverse effects for brain development. The results of this study should reassure clinicians and parents that stopping antiseizure medications in neonates with seizures prior to hospital discharge is safe and potentially beneficial, and hopefully will lead to an evidence-based change in practice."

Dr. Niranjana Natarajan, an assistant professor of pediatric neurology at the University of Washington School of Medicine in Seattle, said, "This study confirms in a rigorous way the suspicions of many neurologists caring for newborns."

"I hope these findings will reassure neurologists and neonatologists that it is safe to discontinue antiseizure medications for this population while they are still in the neonatal intensive-care unit," Dr. Natarajan told Reuters Health by email.

Dr. Glass recommends that clinicians answer these questions before deciding whether to discontinue antiseizure medications:

* Are the seizures due to an acute provoked cause, such as hypoxic-ischemic injury, ischemic, stroke, hemorrhage, or other brain injury?

* Have the seizures stopped for at least 24 hours of EEG recording?

* Has the family been taught what to do and whom to call in case of suspected seizures?

"If the answer is 'yes' to all three questions, it is safe to stop the antiseizure medications," she advised.

SOURCE: https://bit.ly/3i8Q5YS and https://bit.ly/3yMH5OV JAMA Neurology, online May 24, 2021.

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