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Background Zonisamide is one of the anti-parkinsonian agents approved and used in Japan, and it improves motor symptoms and off time in the advanced stage of Parkinson's disease. However, there is no evidence of its efficacy in the early stage of Parkinson's disease. Aim To investigate the effect of zonisamide on the early stage of Parkinson's disease. Methods We consecutively recruited patients with less than 3 years of disease duration who were treated with levodopa/dopa decarboxylase inhibitor only or additional small amounts of dopamine agonists. We evaluated motor severities with the Unified Parkinson's Disease Rating Scale, non-motor severities with the Non-Motor Symptom scale and health-related quality of daily life with the 39 items of the Parkinson's Disease Questionnaire. Patients also evaluated themselves with the Patient Global Impression of Improvement index. Serum zonisamide levels were monitored throughout the study. After the baseline clinical evaluation, patients received 25 mg of open-label zonisamide, and were evaluated for 28 weeks. Results We recruited 13 patients, and 11 patients completed the study. Adjunctive zonisamide significantly improved the Unified Parkinson's Disease Rating Scale part III score and Patient Global Impression of Improvement after the 12th week. The Non-Motor Symptom Scale and summary index of the 39-item Parkinson's Disease Questionnaire showed no significant changes. Mean plasma levels of zonisamide were stable throughout the study. Two patients could not complete because of adverse events. Conclusions Zonisamide can be expected to be safe and beneficial to motor symptoms of Parkinson's disease in the early stage as well as the advanced stage. [ABSTRACT FROM AUTHOR]