Combination Therapy with Zonisamide and Antiparkinson Drugs for Parkinson's Disease: A Meta-Analysis

Background: There is uncertainty about the efficacy and tolerability of zonisamide for Parkinson's disease (PD). Objective: We performed a meta-analysis of zonisamide treatment in PD patients who received antiparkinson drugs such as levodopa. Methods: The primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, wearing-off time, and discontinuation rate due to all causes. Secondary outcome measures were UPDRS total and subscale scores; discontinuation rates due to adverse events, inefficacy, and death; and individual adverse events. Results: Four randomized placebo-controlled trials including 1,068 PD patients were analyzed. All studies were conducted in Japan. UPDRS Part III scores were significantly lower with zonisamide than with placebo (weighted mean difference [WMD], -2.56; 95% confidence interval [CI]; -4.20 to -0.92; p = 0.002). Further, zonisamide significantly decreased the wearing-off time compared with placebo (standardized mean difference, -0.24; 95% CI, -0.39 to -0.09; p = 0.001). Discontinuation rates due to all causes were similar between the zonisamide and placebo groups (risk ratio, 1.29; 95% CI, 0.90 to 1.84; p = 0.16). While zonisamide also decreased both UPDRS Part II (off-time) and UPDRS total scores compared to placebo (UPDRS Part II [off-time] scores: WMD, -0.79; UPDRS total scores: WMD, -2.51), there were no significant differences in other secondary outcomes between the two groups. Conclusions: Our results suggested that zonisamide combination therapy was beneficial in treating motor symptoms in PD patients receiving antiparkinson drugs and was well tolerated in Japanese patients. Future studies in populations other than the Japanese are needed.