Zonisamide: A review of the clinical and experimental evidence for its use in Parkinson's disease

The limitations of currently available therapies in addressing the non motor symptoms of Parkinson's disease (PD) have egged on the search for newer options. Zonisamide has been in use for epilepsy and it was serendipitously found to improve the symptoms of PD in a patient who had both epilepsy and PD. Thereafter, various trials were designed to assess the use of zonisamide in PD. The present article investigates the evidence for use of zonisamide in PD from the various clinical trials that were designed to address this issue. Furthermore, the article also summarizes the various mechanisms of its use in PD as described in various animal experiments. A search protocol was designed with predefined inclusion and exclusion criteria. The databases searched were Pubmed, Ovid medline, Cochrane and clinicaltrials.gov. The data thus generated, was fed into a predesigned format. Most of the clinical trials on zonisamide in PD have come from Japan. Most of these trials used the changes in the Unified Parkinson's Disease Rating Scale (UPDRS) score as the endpoints and the most conclusive evidence is for a dose of 25-50 mg, which caused a change in UPDRS part III (motor symptoms). These patients were on levodopa and other drugs used for PD during the trials. One of the clinical trials conducted in Spain investigates the use of zonisamide in impulse control disorders among 15 patients of PD. Among the many mechanisms postulated, a reduction in levodopa induced quinone formation, protection against mitochondrial impairment and an increase in astroglial cysteine transport, an inhibition of microglial activation, monoamine oxidase-B (MAO-B) inhibition, an increased dopamine release and blockade of calcium channels are the most cited. There is evidence for use of zonisamide in PD in addition to levodopa and other therapies for control of motor symptoms. For now, the evidence for its use in control of non motor symptoms in PD is not enough and needs to be investigated further.