Baker Megan, Huefner Jonathan C, Bellonci Christopher, Hilt Robert, Carlson Gabrielle A
Momentum for Health, San Jose, California, USA.
Boys Town Child and Family Translational Research Center, Boys Town, Nebraska, USA.
J Child Adolesc Psychopharmacol. 2021 Apr;31(3):148-163. doi: 10.1089/cap.2020.0162. Epub 2021 Feb 17.
Prescription of multiple medications concurrently for children and adolescents has increased in recent years. Examination of this practice has been undervalued relative to its incidence. This article reviews studies investigating effectiveness of medication combinations for youth with attention-deficit/hyperactivity disorder (ADHD). A literature search identified studies that combined two or more prescribed medications for the treatment of ADHD. Included studies focused on youth; had study design of randomized controlled trial (RCT), nonrandomized trial, or case review ( > 10); and included an outcome measure of treatment effectiveness. Thirty-nine pertinent studies were identified. All studies combined two medications, with the vast majority including a stimulant ( = 37). The largest group ( = 16) combined stimulant and alpha-agonist, finding greater efficacy than alpha-agonist alone but not stimulant alone in all cases. A few RCTs found benefit from the addition of risperidone or divalproex to stimulant for comorbid aggression. Four studies adding atomoxetine found mixed reports of benefit, including the only small RCT showing no benefit. RCTs with selective serotonin reuptake inhibitors found minimal evidence of benefit for mood or anxiety comorbidities. The best studied combination is stimulant and alpha-agonist; addition of alpha-agonist to stimulant seems effective for residual symptoms of ADHD. Stimulant plus risperidone has the most evidence of efficacy for comorbid aggression or disruptive behavior. Limited support exists for the effectiveness of other medication combinations, including no trials studying three or more medications concurrently. Combinations frequently yielded more side effects, leaving monotherapy preferable if a sufficient treatment response can be achieved.
近年来，儿童和青少年同时开具多种药物处方的情况有所增加。相对于其发生率，对这种做法的研究一直未得到重视。本文回顾了调查药物联合使用对注意力缺陷多动障碍（ADHD）青少年有效性的研究。文献检索确定了将两种或更多种处方药物联合用于治疗ADHD的研究。纳入的研究关注青少年；采用随机对照试验（RCT）、非随机试验或病例回顾（>10）的研究设计；并包括治疗有效性的结果测量。共确定了39项相关研究。所有研究均联合使用两种药物，绝大多数研究（=37）包括一种兴奋剂。最大的一组（=16）联合使用兴奋剂和α-激动剂，发现在所有情况下，联合使用比单独使用α-激动剂更有效，但不比单独使用兴奋剂更有效。一些RCT发现，在兴奋剂中添加利培酮或丙戊酸对合并攻击行为有益。四项添加托莫西汀的研究发现了关于益处的混合报告，包括唯一一项显示无益处的小型RCT。使用选择性5-羟色胺再摄取抑制剂的RCT发现，对合并情绪或焦虑症有益的证据极少。研究最多的联合用药是兴奋剂和α-激动剂；在兴奋剂中添加α-激动剂似乎对ADHD的残留症状有效。兴奋剂加用利培酮对合并攻击行为或破坏性行为最有疗效证据。其他药物联合使用的有效性支持有限，包括没有研究同时使用三种或更多种药物的试验。联合用药通常会产生更多副作用，如果能获得足够的治疗反应，单药治疗更可取。
