Fewer migraine days with zonisamide in children

A retrospective cohort study presented at AAN 2025 has demonstrated that prophylactic zonisamide can significantly reduce headache days per month (HDPM) in paediatric patients with migraine.

Zonisamide worked effectively regardless of whether patients experienced intractable or nonintractable migraine, with the most pronounced effect observed after 2 months of use.

Zonisamide has been used off-label for migraine prevention in children. However, the drug has not been thoroughly studied as a prophylactic for migraine attacks in this population. “In this study, we wanted to prove that what we’ve seen clinically is actually true,” said study investigator Dr Anisa F. Kelley, assistant professor, Feinberg School of Medicine, Northwestern University, and a child neurologist at Ann & Robert H. Lurie Children’s Hospital, both in Chicago, Illinois, US.

Kelley and her team assessed the effectiveness of zonisamide – an antiseizure medication – as a prophylactic treatment for migraines. The study included 256 paediatric patients (mean age 15; 70 percent girls) who were diagnosed with migraine and prescribed zonisamide. The children had a mean age of 15 years, with inclusion criteria for age ranging from 4–18 years. Approximately 70 percent of the participants were girls. Data on headache frequency over time were collected. [AAN 2025, abstract P11.017]

Common neurological disorder

Migraine, characterized by recurrent attacks that can significantly and adversely affect quality of life, is a relatively common neurological disorder among children and adolescents. Kelley said children are unique in that prepuberty, boys experience more migraines than girls, whereas post-puberty, girls have a higher incidence of migraines.

Among the group, 28 percent had intractable migraine or had tried but failed at least two prophylactic medications. Seventy-two percent had experienced nonintractable migraine or had not attempted at least two preventive treatments.

Across the entire cohort, there was a substantial reduction in HDPM, from a median of 18 days per month at baseline to 6 days per month at the first follow-up visit after initiating zonisamide (p<0.001). Patients who followed up within 2–6 months of commencing treatment reported the greatest reductions in migraine days, with a median decrease of 6 HDPM (p=0.01).

The results were consistent across patient subgroups. Both patients with intractable migraines and those with nonintractable migraines showed similar reductions in headache frequency, with a median decrease of 6 HDPM in each group (p<0.001 for both).

An effective prophylaxis

Thirty-four percent of patients transitioned from chronic migraine to episodic migraine after their first visit and following treatment with zonisamide. In contrast, only 4 percent of patients experienced the opposite shift, moving from episodic to chronic migraine.

“Zonisamide appeared to be an effective prophylaxis for both intractable and nonintractable migraine, with the strongest effect seen after at least 2 months of use,” the researchers concluded.

The study adds to the conversation about potential treatment options for youth with migraine and could spur further research — ideally through randomized controlled trials. Future research could compare zonisamide prophylaxis to the current gold standard, topiramate.

Although effective, topiramate comes with burdensome side effects that affect alertness, appetite, and cognition, and it must be taken twice daily.