盐酸哌甲酯控释片治疗注意缺陷多动障碍的多中心、随机、双盲、交叉对照研究

Comparison study of methylphenidate HCl extended-release tablets and placebo in treatment of children with attention deficit hyperactivity disorder: a multicenter, randomized, double-blind, placebo-controlled, cross-over trial

目的 比较盐酸哌甲酯控释片与安慰剂治疗儿童注意缺陷多动障碍(ADHD)的疗效及安全性。方法 采用多中心、随机、双盲交叉对照试验设计。将121例符合美国精神障碍诊断与统计手册第4版注意缺陷多动障碍诊断标准的患儿依照1∶1的比例,随机分为A(先服哌甲酯控释片再服安慰剂)或B(先服安慰剂再服哌甲酯控释片)两个治疗顺序组,分别接受哌甲酯控释片和安慰剂治疗各7d;并于双盲治疗期末评定主要疗效评定指标[由教师评定的Conners注意缺陷/多动伴攻击行为评定量表(IOWAConners量表)注意缺陷/多动(I/O)分项]、次要疗效指标[包括教师评定的对立/违抗(O/D)分项、同伴交往和总体评价量表;家长评定的IOWAConners量表I/O和O/D分项、家庭活动状况和总体评价量表;研究者评定的临床总体印象量表]。结果 (1)疗效:哌甲酯控释片治疗7d后,意向性分析人群和符合方案评估人群的主要疗效指标分析的评分分别为(4 92±3 11)分和(4 80±3 07)分,低于安慰剂组[分别为(6 70±3 67)分和(6 58±3 70)分;均P<0 01];其他次要疗效指标,哌甲酯控释片治疗组的评定结果均明显优于安慰剂治疗组(P<0 01)。(2)不良事件发生率:哌甲酯控释片组为14 9%,安慰剂组为7 4%,两组差异无统计学意义(P>0 05)。

Objective To compare the efficacy and tolerability of methylphenidate extended-release tablets (OROS MPH) and placebo in treating children with attention deficit hyperactivity disorder (ADHD). Methods One hundred58 and twenty-one children with ADHD, all subtypes, aged 6 to 16 years, participated in a multicenter, double-blind, randomized, placebo-controlled, cross-over clinical trial. The diagnosis of ADHD was made according to the 4th edition of Diagnostic Statistical Manual of Mental Disorder criteria. Patients were assigned to one of three dosage (18 mg, 36 mg or 54 mg daily), according to their pre-study or study titrated therapeutic dose regimen. Randomization to OROS MPH or placebo was in a ratio of 1∶1 respectively. Patients were randomized to one of the two treatment sequences, in Sequence A, the patients took OROS MPH on day 1 to day 7, and then OROS placebo on day 8 to day 14; while in Sequence B, the patients took OROS placebo in the first 7 days, and then OROS MPH in the following 7 days. The primary efficacy measurement was IOWA Conners Rating Scale (I&O), and measured on the double blind study day 6 and day 13 by the school teacher.Results Children in the period of OROS MPH showed significantly greater reduction on the I&O core symptoms than children in placebo (the mean scores were 4.92±3.11 and 6.70±3.67, respectively, P<0.01). Meanwhile, OROS MPH showed better efficacy than placebo on all the secondary efficacy measurements (P<0.01). Concerning the adverse events, there was no significant difference between OROS MPH and placebo group (P>0.05), with adverse event incidence of 14.9% and 7.4% in OROS MPH and placebo group, respectively.Conclusion For the efficacy in treatment of patients with ADHD, OROS MPH dosed once a day was superior to placebo with safe tolerability.