University of Texas Health Science Center, San Antonio.
University of Texas Health Science Center, San Antonio.
J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):236-251. doi: 10.1016/j.jaac.2019.12.009. Epub 2020 Jan 30.
Stimulant medications are the most prevalent first-line pharmacotherapy for attention-deficit/hyperactivity disorder, but children with aggressive behavior often receive multiagent treatment. There is sparse evidence for the benefits of adjunctive medications when stimulant monotherapy provides inadequate benefit for aggressive behavior, yet the adverse effects of common adjuncts are well established. This study compared the efficacy in reducing aggressive behavior of risperidone (RISP), divalproex sodium (DVPX), and placebo (PBO) added to stimulant medication among childrenwhose symptoms persisted after individually optimized stimulant treatment.
This trial enrolled 6- to 12-year-old with attention-deficit/hyperactivity disorder, a disruptive disorder, significant aggressive behavior, and prior stimulant treatment. Open, systematically titrated stimulant treatment identified patients with inadequate reductions in aggressive behavior, who were then randomly assigned to receive adjunctive RISP, DVPX, or PBO under double-blinded conditions for 8 weeks. Family-based behavioral treatment was offered throughout the trial. The primary outcome was the parent-completed Retrospective Modified Overt Aggression Scale.
Participants included 175 children (mean [SD] age 9.48 [2.04] years, 19% female). Of participants, 151 completed the stimulant optimization phase, with aggression remitting among 96 (63%), and 45 were randomly assigned to adjunctive treatment groups. The adjunctive RISP group showed greater reductions in aggression ratings than the PBO group (least squares means difference [ΔLSM], -2.33; 95% CI, -3.83 to -0.82; effect size [ES], -1.32), as did the DVPX group (ΔLSM, -1.60; 95% CI, -3.18 to -0.03; ES, -0.91). Mean standardized body mass index scores increased more among RISP-treated participants than participants receiving PBO (ΔLSM, 1.54; 95% CI, 0.68 to 2.40; ES, 0.58).
High response rate during the trial's open stimulant optimization phase suggests that rigorous titration of stimulant medication and concurrent behavioral therapy may avert the need for additional medications. Among nonremitters, RISP and DVPX were efficacious adjunctive treatments, although RISP was associated with weight gain.
Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study); https://www.clinicaltrials.gov; NCT00794625.
兴奋剂药物是治疗注意缺陷/多动障碍的最常用一线药物疗法，但具有攻击性行为的儿童通常接受联合药物治疗。虽然兴奋剂单药治疗对攻击性行为的益处不足时，辅助药物的益处证据很少，但常见辅助药物的不良反应却已有充分的证据。本研究比较了在个体化优化的兴奋剂治疗后症状持续存在的儿童中，利培酮（RISP）、丙戊酸钠（DVPX）和安慰剂（PBO）添加到兴奋剂药物中对减少攻击性行为的疗效。
本试验纳入了 6 至 12 岁患有注意缺陷/多动障碍、破坏性行为、明显攻击性行为和既往兴奋剂治疗的儿童。开放、系统滴定的兴奋剂治疗确定了攻击性行为减少不足的患者，然后在双盲条件下随机分配接受辅助 RISP、DVPX 或 PBO 治疗 8 周。在整个试验过程中提供了以家庭为基础的行为治疗。主要结局是家长完成的回顾性改良显性攻击量表。
共有 175 名儿童（平均[标准差]年龄 9.48[2.04]岁，19%为女性）参与了研究。在参与者中，有 151 名完成了兴奋剂优化阶段，其中 96 名（63%）的攻击行为缓解，45 名被随机分配到辅助治疗组。辅助 RISP 组的攻击行为评分下降幅度大于 PBO 组（最小二乘均数差值[ΔLSM]，-2.33；95%置信区间，-3.83 至-0.82；效应量[ES]，-1.32），DVPX 组也如此（ΔLSM，-1.60；95%置信区间，-3.18 至-0.03；ES，-0.91）。与接受 PBO 的参与者相比，接受 RISP 治疗的参与者的平均标准化体重指数评分增加更多（ΔLSM，1.54；95%置信区间，0.68 至 2.40；ES，0.58）。
在试验的开放性兴奋剂优化阶段，高反应率表明严格滴定兴奋剂药物和同时进行行为治疗可能避免需要额外药物治疗。在未缓解者中，RISP 和 DVPX 是有效的辅助治疗方法，尽管 RISP 与体重增加有关。
注意缺陷多动障碍儿童联合药物治疗对攻击行为的疗效（SPICY 研究）；https://www.clinicaltrials.gov；NCT00794625。
