Zonisamide Shows Promise as a Preventive Migraine Treatment for Kids and Teens

April 5, 2025

A new study suggests that zonisamide (Zonegran), a medication traditionally used to treat seizures, may help reduce migraine days in children and teens.

The research, led by Dr. Anisa Kelley of Northwestern University Feinberg School of Medicine, reviewed health records of 256 children and teens diagnosed with migraines who were prescribed zonisamide as a preventive treatment. Among these participants, 28% had difficult-to-treat migraines, defined as migraines that had not responded to at least two other medications.

The researchers found that the median number of headache days per month dropped from 18 to six across all participants after starting zonisamide.

The greatest improvement was observed in the subgroup that followed up two to six months after beginning the medication, suggesting zonisamide is most effective after at least two months of use.

Zonisamide appeared to benefit both those with difficult-to-treat migraines and those without.

Zonisamide shares similarities with topiramate (Topamax), the only FDA-approved preventive migraine medication for children and teens. Both drugs are anticonvulsants that can help stabilize neuronal activity linked to migraines. However, zonisamide may have an advantage: it tends to cause fewer side effects compared to topiramate. The potential side effects include cognitive issues like memory and concentration difficulties, fatigue, weight loss, and others.

Dr. Kelley emphasized that while the findings are promising, the study has limitations. It did not include a control group of participants who were not taking zonisamide, and it relied on health record reviews rather than randomized clinical trials. Further research is needed to confirm these results and establish zonisamide’s effectiveness more conclusively.

I have been preferring zonisamide over topiramate in both children and adults. Both drugs have similar mechanisms of action and similar side effects, but topiramate causes more cognitive side effects, irritability, and depression. Topiramate is also more likely to cause kidney stones and severe metabolic acidosis. In older adults, both can cause osteoporosis.

Written by
Alexander Mauskop, MD
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