Prophylactic Zonisamide for Migraine in Pediatric Patients: Is It Effective?

Prophylactic zonisamide can significantly reduce headache days per month (HDPM) in pediatric patients with migraine, according to study results presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California.

In this retrospective cohort study, researchers assessed the effectiveness of zonisamide as a prophylactic treatment for pediatric patients with migraine. Zonisamide, an anti-seizure medication, has been used off-label for migraine prevention in children, but its effectiveness in this context has not been well-documented.

The study included a cohort of 256 pediatric patients (mean age, 15; girls, 70%) diagnosed with migraine who were prescribed zonisamide to reduce headache frequency. Among the group, 28% were diagnosed with intractable migraines, a condition that is difficult to manage and treat effectively.

The researchers sought to assess changes in the number of HDPM after initiating zonisamide treatment.

The researchers found 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 (95% CI, -12, -8.5; P <.001). Patients who followed up within 2 to 6 months of starting treatment saw the greatest improvements, with a median decrease of 6 HDPM (Z=2.18, P =.01).

The results were consistent across different patient subgroups. Both patients with intractable migraines and those with non-intractable migraines showed similar reductions in headache frequency, with a median decrease of 6 HDPM in each group (95% CI, -10, -3; P <.001; 95% CI, -13.75, -10; P <.001, respectively).

A total of 34% of patients transitioned from chronic migraine to episodic migraine after their first visit and receiving zonisamide treatment. In comparison, only 4% of patients experienced the opposite shift, moving from episodic to chronic migraine.

“Zonisamide appeared to be an effective prophylaxis for both intractable and non- intractable migraine, with the strongest effect seen after at least 2 months of use,” the researchers concluded. “Future research could compare zonisamide prophylaxis to the current gold standard, topiramate.”