Kowatch Robert A, Scheffer Russell E, Monroe Erin, Delgado Sergio, Altaye Mekibib, Lagory Denise
1 The Ohio State University Wexner Medical Center/Nationwide Children's Hospital , Columbus, Ohio.
J Child Adolesc Psychopharmacol. 2015 May;25(4):306-13. doi: 10.1089/cap.2014.0166.
The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children, 3-7 years of age, with bipolar I disorder (BPD), during a mixed or manic episode.
Forty-six children with Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode, were recruited over a 6 year period from two academic outpatient programs for a double-blinded, placebo-controlled trial in which subjects were randomized in a 2:2:1 ratio to risperidone solution, valproic acid, or placebo.
After 6 weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores change, adjusted for baseline YMRS scores, from baseline by treatment group was: Valproic acid 10.0±2.46 (p=0.50); risperidone 18.82±1.55 (p=0.008); and placebo 4.29±3.56 (F=3.93, p=0.02). The mixed models for repeated measure (MMRM) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects (p=0.008) but not for valproic acid-treated subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone over 6 weeks led to increased prolactin levels, liver functions, metabolic measures, and weight/body mass index (BMI). Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit.
In this small sample of preschool children with BPD, risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did not. The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics, and that, therefore, frequent laboratory and weight monitoring are warranted.
本研究的目的是确定丙戊酸与利培酮在3至7岁患有双相I型障碍（BPD）且处于混合或躁狂发作期的儿童中的疗效和安全性。
在6年期间，从两个学术门诊项目招募了46名符合《精神疾病诊断与统计手册》第4版，文本修订版（DSM-IV-TR）双相情感障碍、躁狂、轻躁狂或混合发作诊断标准的儿童，进行一项双盲、安慰剂对照试验，受试者按2:2:1的比例随机分为利培酮溶液组、丙戊酸组或安慰剂组。
治疗6周后，根据基线Young躁狂评定量表（YMRS）总分变化进行调整，各治疗组从基线开始的变化情况为：丙戊酸组10.0±2.46（p = 0.50）；利培酮组18.82±1.55（p = 0.008）；安慰剂组4.29±3.56（F = 3.93，p = 0.02）。重复测量混合模型（MMRM）分析发现，利培酮治疗组与安慰剂治疗组之间存在显著差异（p = 0.008），而丙戊酸治疗组与安慰剂治疗组之间无显著差异（p = 0.50）。6周的利培酮治疗导致催乳素水平、肝功能、代谢指标以及体重/体重指数（BMI）升高。丙戊酸治疗导致体重/BMI升高，总红细胞（RBC）、血红蛋白和血细胞比容降低。
在这个患有BPD的学龄前儿童小样本中，利培酮相对于安慰剂显示出明显疗效，而丙戊酸则未显示出疗效。实验室检查和体重结果表明，患有BPD的年幼儿童对这两种精神药物的作用更敏感，因此，有必要频繁进行实验室检查和体重监测。
