From Neurology (M.M.), National Center Hospital, National Center of Neurology and Psychiatry, Tokyo; Health Management Center (T.O.), Yokohama City University; Neurology (K.H.), National Hospital Organization, Sagamihara National Hospital, Kanagawa; Sumitomo Dainippon Pharma Co., Ltd. (S.I., M.N., M.T.), Tokyo; and Clinic Ian Center Minami (K.K.), Kanagawa, Japan.
Neurology. 2018 Feb 20;90(8):e664-e672. doi: 10.1212/WNL.0000000000005010. Epub 2018 Jan 24.
To investigate the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with dementia with Lewy bodies (DLB).
This phase 2, placebo-controlled, randomized, double-blind study consisted of run-in (placebo, 4 weeks) and treatment (placebo or zonisamide 25 or 50 mg once daily, 12 weeks) periods. Outpatients diagnosed with probable DLB were eligible for inclusion. The primary endpoint was the change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) part 3 total score at week 12. Cognitive function, behavioral and psychological symptoms of dementia (BPSD), caregiver burden, other UPDRS parts as secondary endpoints, and safety were also assessed.
Overall, 158 patients with DLB received the study drug; 21 discontinued during treatment and 137 completed treatment. Improvement in UPDRS part 3 total score at week 12 was significantly greater in the zonisamide 50 mg group compared with placebo (between-group difference -4.1; 95% confidence interval -6.8 to -1.4; = 0.003). Zonisamide did not worsen cognitive function, BPSD, or caregiver burden. The overall incidence of adverse events was higher in the zonisamide 50 mg than the 25 mg and placebo groups (65.3%, 43.1%, and 50.0%, respectively); similar rates of serious adverse events were observed among all groups.
Zonisamide (adjunctive to levodopa) improved parkinsonism accompanying DLB without worsening cognitive function or psychiatric symptoms.
JapicCTI-122040.
This study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well-tolerated in patients with DLB.
研究佐米曲普坦作为路易体痴呆（DLB）伴帕金森病患者左旋多巴辅助治疗的疗效和安全性。
这是一项 2 期、安慰剂对照、随机、双盲研究，包括导入期（安慰剂，4 周）和治疗期（安慰剂或佐米曲普坦 25 或 50mg 每日 1 次，12 周）。符合可能的 DLB 诊断的门诊患者有资格入组。主要终点是治疗 12 周时统一帕金森病评定量表（UPDRS）第 3 部分总分的基线变化。还评估了认知功能、痴呆的行为和心理症状（BPSD）、照顾者负担、其他 UPDRS 部分作为次要终点以及安全性。
共有 158 例 DLB 患者接受了研究药物治疗；21 例在治疗期间停药，137 例完成了治疗。与安慰剂相比，佐米曲普坦 50mg 组在第 12 周时 UPDRS 第 3 部分总分的改善显著更大（组间差异-4.1；95%置信区间-6.8 至-1.4； = 0.003）。佐米曲普坦未加重认知功能、BPSD 或照顾者负担。佐米曲普坦 50mg 组的总体不良事件发生率高于佐米曲普坦 25mg 组和安慰剂组（分别为 65.3%、43.1%和 50.0%）；所有组均观察到相似的严重不良事件发生率。
佐米曲普坦（与左旋多巴联合使用）改善了 DLB 伴发的帕金森病，且不恶化认知功能或精神症状。
JapicCTI-122040。
这项研究提供了 I 级证据，表明佐米曲普坦（与左旋多巴联合使用）可改善 DLB 患者的帕金森病，且耐受良好。
