From the Guidelines
Zonisamide is not FDA-approved as an anti-obesity medication, but it may be used off-label for weight loss due to its pharmacologic properties similar to topiramate, as noted in the 2022 study published in Gastroenterology 1. When considering zonisamide for weight loss, it's essential to weigh the potential benefits against the risks, including common side effects like dizziness, fatigue, cognitive impairment, and kidney stones.
- The typical starting dose of zonisamide is 100 mg daily, gradually increasing to 200-400 mg daily in divided doses, with a maximum of 600 mg daily.
- Zonisamide works by blocking sodium and calcium channels in the brain and enhancing GABA activity, which helps reduce abnormal electrical activity that causes seizures.
- Patients should maintain adequate hydration to reduce kidney stone risk and monitor for rare but serious side effects like skin rashes or suicidal thoughts.
- Zonisamide requires gradual dosage adjustments both when starting and discontinuing to prevent withdrawal seizures.
- It should be used cautiously in patients with kidney or liver impairment and may interact with other medications that affect the central nervous system. As an alternative to topiramate, zonisamide may be considered for weight loss, particularly in patients who experience excessive side effects from topiramate, as suggested in the 2018 study published in the Journal of Neurology, Neurosurgery and Psychiatry 1.
- A study published in the British Journal of Pharmacology in 2017 found that zonisamide decreased AHI and ODI in overweight/obese OSA patients, although it was less effective than CPAP treatment 1. Overall, while zonisamide may be used off-label for weight loss, its use should be carefully considered and monitored due to its potential side effects and interactions. The decision to use zonisamide for weight loss should be based on individual patient needs and medical history, and patients should be closely monitored for potential side effects and interactions, as recommended in the 2022 study published in Gastroenterology 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Mechanism of Action
- Zonisamide has a unique combination of multiple mechanisms of action, including blocking voltage-gated sodium channels, reduction of T-type calcium channel currents, and enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition 2, 3, 4
- These mechanisms of action are potentially complementary with concomitant antiepileptic drugs (AEDs) 3
Efficacy and Safety
- Zonisamide has demonstrated safety and efficacy against a multitude of epilepsy and seizure types, including both partial and generalized seizures 2, 5
- Zonisamide is well tolerated, with the majority of adverse events being mild-to-moderate and generally manageable 3, 6
- The tolerability of zonisamide has also been shown to improve with slower drug titration and duration of drug treatment 3
Clinical Use
- Zonisamide is licensed in Europe and the USA for use as adjunctive therapy in adult patients with partial onset epilepsy 3
- Zonisamide is also indicated in the EU as monotherapy in the treatment of partial seizures, with or without secondary generalization, in adults with newly diagnosed epilepsy 6
- Zonisamide has International League Against Epilepsy level A evidence for efficacy/effectiveness as initial monotherapy for adults with partial-onset seizures 5
Formulations and Special Populations
- Zonisamide is available in multiple formulations 4
- Zonisamide has been used in pediatric and adult patients in Japan for over 2 decades, and has been licensed in Korea for a broad spectrum of epilepsies in adults and children 2, 5
- Zonisamide is suitable for use in special populations, including children, elderly patients, and women of childbearing age 5