Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Pediatrics. 2023 Feb 1;151(2). doi: 10.1542/peds.2022-059574.
All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome.
This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit.
Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences -3.44, 95% confidence interval -6.09 to -0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events.
Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.
所有经美国食品和药物管理局批准用于妥瑞氏综合征的药物均为抗精神病药，但由于体重增加、代谢变化和药物引起的运动障碍等风险，其使用受到限制。几项小型试验表明，一种新型、选择性多巴胺 1 受体拮抗剂 ecopipam 可降低抽动症的严重程度，且发生这些不良反应的风险较低。本试验旨在进一步评估 ecopipam 治疗中重度妥瑞氏综合征儿童和青少年的疗效、安全性和耐受性。
这是一项多中心、随机、双盲、安慰剂对照的 2b 期试验。年龄为 6 岁至<18 岁、基线耶鲁总体抽动严重程度评分总抽动评分≥20 的受试者按 1:1 随机分为 ecopipam 组（n=76）或安慰剂组（n=77）。主要终点是 12 周内耶鲁总体抽动严重程度评分总抽动评分的平均变化。次要终点是妥瑞氏综合征严重程度的临床总体印象。在每次研究访视时评估安全性和耐受性。
与安慰剂组相比，ecopipam 组的总抽动评分从基线到 12 周显著降低（最小二乘均数差值-3.44，95%置信区间-6.09 至-0.79，P=0.01）。ecopipam 组的妥瑞氏综合征严重程度的临床总体印象也有较大改善（P=0.03）。安慰剂组的体重增加更为明显。未发现代谢或心电图变化。头痛（15.8%）、失眠（14.5%）、疲劳（7.9%）和嗜睡（7.9%）是最常见的不良反应。
在妥瑞氏综合征儿童和青少年中，ecopipam 可显著降低抽动症的严重程度，且无常见抗精神病药相关不良反应的明显证据。
