Panda Prateek Kumar, Panda Pragnya, Dawman Lesa, Mishra Anand Santosh, Kumar Vinod, Sharawat Indar Kumar
Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.
Department of Neurology, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India.
CNS Drugs. 2025 Feb;39(2):127-142. doi: 10.1007/s40263-024-01140-w. Epub 2024 Dec 27.
Ecopipam is a selective antagonist of the dopamine D1 receptor, and its efficacy and safety have recently been explored in several clinical trials involving patients with Tourette syndrome (TS). The objectives of this systematic review were to determine the pooled estimate for efficacy [in terms of reduction in tic Yale Global Tic Severity Scale (YGTSS) scores] and safety of oral ecopipam in subjects with TS.
All clinical trials that explored the efficacy and/or safety of ecopipam in patients with TS were included to determine the pooled estimate for change in YGTSS, Clinical Global Impression (CGI)-TS, and the severity of comorbid attention-deficit hyperactive disorder (ADHD), obsessive compulsion disorder (OCD), and depressive symptoms, as well as the nature and frequency of adverse effects. Case-series, retrospective studies, and case reports were excluded. Databases, such as PUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and SCOPUS were searched to identify these trials using suitable combination of MESH terms/keywords on 15 June 2024. ROB 2.0 and ROBINS-I tool were used to assess the risk of bias in included randomized-controlled trials (RCTs) and non-randomized intervention studies, respectively, and the GRADE system to determine the certainty of the collated evidence.
A total of 96 records were identified in the database search and 31 records were screened after removing duplicates. After excluding 23 irrelevant records, the full-text review included 8 records. Finally, six publications from three completed clinical trials (two RCTs, with one having an open-label extension) and one ongoing clinical trial were included. A total of 251 participants were included. The pooled estimate for mean change in YGTSS-TTS from baseline to the completion of the randomization period was statistically better in the ecopipam group compared with the placebo group [mean difference: - 3.0, 95% (confidence interval (CI) - 4.2 to - 1.9, I = 55%, p < 0.0001]. The ecopipam group also fared statistically better in terms of YGTSS-motor tic score, phonic tic score, as well as CGI-TS-S (p < 0.0001). Changes in depressive and obsessive-compulsive symptoms were comparable in both groups, as well as the incidence of adverse effects.
Ecopipam is effective in reducing the severity of tics in subjects with TS and has a good safety profile. However, only a limited number of studies were included in the review, with some having small sample sizes and short duration of follow-up.
依可哌胺是一种多巴胺D1受体选择性拮抗剂，其有效性和安全性最近在多项涉及抽动秽语综合征（TS）患者的临床试验中得到了探索。本系统评价的目的是确定口服依可哌胺对TS患者的疗效（以抽动秽语综合征耶鲁综合抽动严重程度量表（YGTSS）评分降低来衡量）和安全性的汇总估计值。
纳入所有探索依可哌胺对TS患者有效性和/或安全性的临床试验，以确定YGTSS、临床总体印象量表（CGI）-TS以及共病的注意力缺陷多动障碍（ADHD）、强迫症（OCD）和抑郁症状严重程度变化的汇总估计值，以及不良反应的性质和频率。排除病例系列研究、回顾性研究和病例报告。于2024年6月15日使用适当的医学主题词/关键词组合检索PUBMED、EMBASE、Cochrane对照试验中央注册库和SCOPUS等数据库，以识别这些试验。分别使用ROB 2.0和ROBINS-I工具评估纳入的随机对照试验（RCT）和非随机干预研究中的偏倚风险，并使用GRADE系统确定整理证据的确定性。
在数据库检索中总共识别出96条记录，去除重复记录后筛选出31条记录。排除23条无关记录后，全文审查纳入8条记录。最后，纳入了来自三项已完成临床试验（两项RCT，其中一项有开放标签扩展）的六篇出版物以及一项正在进行的临床试验。总共纳入251名参与者。与安慰剂组相比，依可哌胺组从基线到随机化期结束时YGTSS-TTS平均变化的汇总估计值在统计学上更好[平均差异：-3.0，95%置信区间（CI）-4.2至-1.9，I² = 55%，p < 0.0001]。依可哌胺组在YGTSS运动性抽动评分、发声性抽动评分以及CGI-TS-S方面在统计学上也表现更好（p < 0.0001）。两组的抑郁和强迫症状变化以及不良反应发生率相当。
依可哌胺可有效降低TS患者的抽动严重程度，且安全性良好。然而，本评价仅纳入了数量有限的研究，其中一些研究样本量小且随访时间短。
