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
Continue reading
November 15, 2025
Cluster headaches
Cluster headaches and solar activity
It was an unusual week at the New York Headache Center. After months of relative calm, my schedule suddenly filled with cluster headache patients—one even consulting me virtually from Saudi Arabia. The influx came right after a G5-level geomagnetic storm, one of the strongest solar events in recent memory.
Read article
November 10, 2025
Alternative Therapies
A Week of Meditation Changes Brains and Bodies
A week-long meditation retreat produces dramatic changes in brain and metabolic functions
Read article
October 21, 2025
Alternative Therapies
Meditation is better than slow breathing exercise in reducing pain
A new study published in the journal PAIN by Dr. A. Amorim and her colleagues at the University of California San Diego examined how mindfulness meditation reduces pain. The findings help clarify whether mindfulness meditation is more effective than simple slow breathing for pain relief.
Read article