最适剂量哌甲酯治疗注意缺陷多动障碍疗效的影响因素

目的:在汉族注意缺陷多动障碍(ADHD)儿童中研究系统哌甲酯剂量滴定方案的疗效、安全性及疗效影响因素,寻找潜在的疗效预测指标.方法:本研究为开放性设计.对符合美国《精神障碍诊断与统计手册(第4版)》(DSM-Ⅳ)中ADHD诊断标准的患儿给予系统的哌甲酯剂量滴定,达到疗效最好、副作用最小的最适剂量.以教师填写的ADHD评定量表(ADHD-RS-Ⅳ)为主要疗效评价指标;以教师填写的简明Conners儿童行为问卷,父母填写的ADHD评定量表、Conners儿童行为问卷为次要疗效评价指标.采用配对样本t检验比较治疗前后各量表评分的差异.收集潜在的疗效影响因素资料,包括就诊时症状严重程度、智商、感觉统合能力、学习成绩等.对于连续型变量采用相关分析,对二分变量采用方差分析检验各因素对行为量表减分的影响.结果:完成剂量滴定患者的最终处方日剂量平均为(17.3±7.7) mg,以体重计算平均为(0.45±0.11) mg/(kg·d).治疗前后各量表评分的差异均有统计学意义(教师ADHD症状评定量表总分在治疗前为30.25±9.16,治疗后为19.87±10.03,P＜0.001).无论是哌甲酯日剂量还是体重剂量均与疗效无关.在所有研究的因素中,就诊时症状的严重程度与药物疗效呈正相关(r=0.437～0.567, P＜0.001);韦氏智商C因子与教师量表减分呈弱的正相关(控制治疗前症状严重程度后,偏相关系数r'=0.235～0.309, P＜0.01);对于共患学习困难的患儿,教师评定量表各项减分(总分7.35±7.67,注意分4.85±4.54,多动冲动分2.50±4.12)均低于无学习困难者(总分12.33±10.42,注意分6.96±6.00,多动冲动分5.32±5.37,P＜0.05);家长评分中,有前庭平衡功能失调的患儿的多动冲动分的改善(6.34±5.72)优于前庭平衡功能正常者(3.98±4.84,P＜0.01),而在教师评分中,注意分的改善较差(前庭平衡功能失调者5.34±5.70,正常者7.43±5.51,P＜0.05).结论:哌甲酯系统剂量滴定方案治疗汉族儿童ADHD安全有效.疗效的个体差异与剂量无关.影响疗效的可能因素包括治疗前症状的严重程度、韦氏智商C因子、共患学习困难和前庭平衡功能失调.

Factors affecting therapeutic effect of ADHD treated by optimal dose of methylphenidate

OBJECTIVE: To explore the therapeutic effect, security and influencing factors of methylphenidate titration program, try to find the potential predicting index of therapeutic effect. METHODS: This study was openly designed. The patients who were fit for DSM-IV diagnosis criteria of attention deficit hyperactivity disorder (ADHD) underwent systematic methylphenidate titration treatment until they attained the most optimal dose with best therapeutic effect and minimal side effects. The primary evaluative index of therapeutic effect was ADHD rating scale filled by teachers (ADHD-RS-IV), and secondary index included abbreviated Conners questionnaire filled by teachers, ADHD rating scale and Conners questionnaire filled by parents. The matching sample t analyses were used, then the differences of rating scale between pre and post treatment were compared. The potential influencing factors information of therapeutic effects including symptom severity degree when visiting, IQ, sensory integration capability and achievement of school etc. were collected. Finally, the correlation analysis was used for continuous variables and variance analysis for dichotomization variables to analyze and check the factors' influence of declining scores of behavior scale. RESULTS: The final prescribed daily dose for patients who completed dose titration was (17.3+/-7.7) mg on average, computed by kilo bodyweight was (0.45+/-0.11) mg/(kg x d). All the scale scores between pre and post treatment were significantly different (the pre-treatment score of ADHD rating scale completed by teachers was 30.25+/-9.16, and post-treatment score were 19.87+/-10.03 ,P<0.001). Neither daily dose nor kilo bodyweight dose of methylphenidate had correlation with therapeutic effect. Among all the factors, symptom severity degree was positively correlated with therapeutic effect (r=0.437-0.567, P<0.01);the C factor of Wechsler Intelligence Scale had weak positive correlation with declining score of the teachers' scale (after controlling the symptom severity degree pre and post treatment, the coefficient of partial correlation r'=0.235-0.309, P<0.01); the patients with learning disorder had less declining score of teachers' rating scale (total score 7.35+/-7.67,inattention score 4.85+/-4.54,hyperactivity-impulsivity score 2.50+/-4.12) than those without learning difficulty (total score 12.33+/-10.42,inattention score 6.96+/-6.00, hyperactivity-impulsivity score 5.32+/-5.37,P<0.05);the amelioration of the hyperactivity and impulsivity scores of the parents' rating of children with vestibular equilibrium function disorders (6.34+/-5.72)was better than those without vestibular equilibrium function disorders (3.98+/-4.84,P<0.01),while the inattention scores were worse (for those with vestibular equilibrium function disorders 5.34+/-5.70,for those without vestibular equilibrium function disorders 7.43+/-5.51,P<0.05). CONCLUSION: Systematic methylphenidate titration program is safe and effective for Han-Chinese children. The individual variation of therapeutic effect has no association with dose. The possible effecting factors include the symptom severity degree, C factor of Wechsler Intelligence Scale, learning difficulty and vestibular equilibrium function disorders.