甲氧氯普胺对抽动秽语综合征症状及其智力、记忆功能的影响(英文)

Effects of metoclopramide on the symptoms as well as intelligence and memory in Tourette syndrome

背景:抽动秽语综合征使用镇静药有效,但急性肌张力不全,动眼危象等副反应和迟发运动障碍的危险性导致对新治疗方法的探索。目的:证明甲氧氯普胺控制抽动秽语综合征症状、改善智力、记忆的疗效及无锥外系副反应的优势。设计:随机对照实验、盲法评估。单位:中南大学湘雅医院神经内科,湖南中医研究所,南宁市第一人民医院神经内科,中南大学公共卫生学院。对象:选择50例抽动秽语综合征患者来自2000-01/2001-06湘雅医院神经内科抽动症专科门诊熏家长同意配合本科药物治疗及定期复诊观察。其中男38例,女12例;年龄5～21年,平均年龄(10.4±4.2)岁。50例患者随机分为甲氧氯普胺组、氟哌啶醇组,每组25例。方法:两组均服用甲氧氯普胺和氟哌啶醇去标签的100片瓶装白色药片,瓶上标记Ⅰ或Ⅱ为各药的相应代称熏定期复诊时由专人发放。药量:Ⅰ号药0.5～2mg/(kg·d),Ⅱ号药0.05mg/(kg·d),分3或4次口服(剂量个体化原则)。甲氧氯普胺组重度以上抽动秽语综合征患者,初诊时接受专职护师执行的Ⅰ号药10mg肌注,2次/d,2～4d不等。①治疗前和治疗2,4,8,16周患者的病情程度采用美国耶鲁抽动程度综合量表评估(总分100分,分数越高,病情程度、综合损伤越重)。②临床疗效根据抽动秽语综合征患者治疗前后美国耶鲁抽动程度综合量表减分率变化进行评估。③药物的副反应采用Asberg副反应量表评估,分数越低副反应越少。④抽动秽语综合征患者治疗前、治疗3个月认知功能的状况,采用韦氏智商量表(包括语言量表和操作量表两部分,共11个分测验)、记忆商量表(共有10项分测验,记忆商数如果低于标准分,说明其记忆功能存在问题)评估。主要观察指标:①两组患者治疗前后美国耶鲁抽动程度综合量表评分。②两组患者疗效比较。③两组患者治疗前后韦氏智商、记忆商。④两组患者Asberg副反应量表评分。结果:50例患者全部进入结果分析。①两组患者治疗前后美国耶鲁抽动程度综合量表评分:与治疗前比较,治疗后两组患者的美国耶鲁抽动程度综合量表记分均显著减少,甲氧氯普胺组2,4,8,16周稳态减少,氟哌啶醇组2,8,16周递减,第2周和第4周时基本接近。②两组患者疗效比较:两组好转率均为92%(23/25),P>0.05。③两组患者治疗前后韦氏智商:甲氧氯普胺组和氟哌啶醇组治疗后均明显高于治疗前眼93.0±15.1,87.0±14.6;93.2±17.0,87.3±13.6,(t=3.43,2.3,P<0.01)演。④两组患者治疗前后韦氏记忆商:仅甲氧氯普胺组治疗后高于治疗前眼87.8±12.8,75.8±15.5,(t=3.30,P<0.01)演。⑤Asberg副反应量表评分:甲氧氯普胺组低于氟哌啶醇组眼(1.00±0.76),(3.24±1.40)分,(t=7.05,P<0.01)演。结论:甲氧氯普胺和氟哌啶醇均有控制抽动秽语综合征患者抽动症状熏改善智力、记忆功能的疗效,但甲氧氯普胺副反应轻微,尤其无锥体外系副反应。

BACKGROUND： Neuroleptic agents are effective in treating Tourette syndrome （TS）. Side effects such as acute myodystonia and oculogyric crisis as well as the risk of delayed dyskinesia have led to search for ahemative therapy. OBJECTIVE： To explore the effects of metoclopramide in controlling the symptoms of TS and improving the intelligence and memory function without causing extrapyramidal side effects. DESIGN： Randomized controlled trial and blind method. SETTING： Neurological Department of Xiangya Hospital Affiliated to Central South University; Institute of Traditional Chinese Medicine of Hunan Province; Neurological Department of the First People＇s Hospital of Nanning City; Public Health College of Central South University. PARTICIPANTS： Fifty patients with TS came from Tic Specialty Clinic, Neurological Department of Xiangya Hospital, between January 2000 and June 2001. Patients and their family members agreed to accept our medical treatment and reexamination on fixed dates. There were 38 males and 12 females aged 5-21 years with the mean age of （10.4±4.2） years. All of them were divided into metoclopramide group and haloperidol group with 25 in each group. METHODS： Metoclopramide and haloperidol were white tablets bottled without tag （100 tablets of white color medicine in each bottle）. The two types of medicine in each bottle were marked Ⅰ or Ⅱ, respectively. The blind method （patients, their parents and evaluation blinded） was used to test the real biochemical nature of the medicine. Medicine was given by a specific doctor on regular days （2, 4, 8, 16 weeks） to patients on their revisit. The daily dose of metoclopramide for body weight was 0.5-2 mg/（kg·d） and haloperidol was 0.05mg/（kg·d） and was assigned 3-4 times （principle of dose individuality）. In addition, TS patients with severe tics in metoelopramide group would receive metoelopramide 10 mg by intramuscular injection twice a day, at the initial treatment for 2-4 days. ① Before and after treatment, TS severity of patients at weeks 2, 4, 8 and 16 was evaluated by YGTSS （the total score was 100 points; the higher the score, the more severe the condition and overall impairment）. ② The clinical curative effect of the medicines was evaluated with YGTSS deduction rate before and after treatment. ③ Asberg side-effect rating score： The lower the score, the fewer and milder the side effects. ④ The cognition function was evaluated with WISC score before treatment and after 3 months of treatment. WISC consisted of language and performance components with 11 subtests, while memory scale category had 10 subtests （memory score lower than the standard indicated problem in memory function）. MAIN OUTCOME MEASURES： ① Comparison of YGTSS in patients before and after treatment; ② comparison of efficacy in patients of the two groups; ③ comparison of intelligence quotient and memory quotient of patients before and after treatment; ④ adverse events and side effects. RESULTS： Totally 50 patients entered the final analysis. ① Comparison of Tourette＇s syndrome in patients before and after treatment： YGTSS score in the two groups decreased significantly after treatment. The comparison of the differences suggested that metoclopramide had better curative effect than haloperidol. In metoclopramide group, YGTSS score was reduced steadily at weeks 2, 4, 8 and 16. In haloperidol group, YGTSS score was also reduced steadily at weeks 2, 8 and 16, but it was similar at week 2 and week 4. ② Comparison of efficacy in patients of the two groups： The total clinical curative effect rate was 92% （23/25） in both groups withoutany difference （P 〉 0.05）. ③ Comparison of intelligence quotient before and after treatment： In both metoclopramide group and haloperidol group it was higher after treatment than before treatment （93.0±15.1, 87.0±14.6; 93.2±17.0, 87.3±13.6, t=3.43, 2.3, P〈0.01）. ④ Comparison of memory quotient of patients before and after treatment： It was higher only in metoclopramide group after treatment than before treatment （87.8±12.8, 75.8±15.5, t=3.30, P〈0.01）. ⑤ Score of Asberg side effects： It was lower in metoclopramide group than in haloperidol group [（1.00±0.76）, （3.24±1.40） points, t=7.05, P〈0.01]. CONCLUSION： The results suggest that metoclopramide is effective in controlling the symptoms of TS and improving intelligence and memory function. Metoclopramide causes mild side effects, but no extrapyramidal side effects.