阿立哌唑口崩片作为青少年精神分裂症的维持治疗：一项为期 52 周、随机、安慰剂对照停药研究的结果。

Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study.

机构信息

Zucker Hillside Hospital, Glen Oaks, NY, and Hofstra Northwell School of Medicine, Hempstead, NY.

Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, NJ.

出版信息

J Am Acad Child Adolesc Psychiatry. 2017 Sep;56(9):784-792. doi: 10.1016/j.jaac.2017.06.013. Epub 2017 Jul 8.

DOI:10.1016/j.jaac.2017.06.013

PMID:28838583

Abstract

OBJECTIVE

To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia.

METHOD

This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed.

RESULTS

Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline.

CONCLUSION

Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia.

CLINICAL TRIAL REGISTRATION INFORMATION

Efficacy and Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia; http://clinicaltrials.gov/; NCT01149655.

摘要

目的

评估阿立哌唑（一种多巴胺 D 受体部分激动剂）作为青少年精神分裂症门诊患者的维持治疗的疗效、安全性和耐受性。

方法

这是一项多中心、双盲、安慰剂对照、随机撤药设计试验。参与者为年龄在 13 至 17 岁、符合精神分裂症诊断标准（DSM-IV-TR）的患者，首先从其他口服抗精神病药物（4-6 周）交叉滴定，然后口服阿立哌唑 10 至 30mg/d 稳定（7-21 周），最后随机 2:1 进入口服阿立哌唑或安慰剂的双盲维持期（≤52 周）。主要终点是从随机分组到精神病症状恶化/复发的时间。评估安全性和耐受性。

结果

201 名入组患者中，146 名在双盲维持期随机分为阿立哌唑（n=98）或安慰剂（n=48）组。与安慰剂相比，阿立哌唑治疗与精神病症状恶化/复发时间延长显著相关（风险比，0.46 [95% CI 0.24-0.88]；p=0.016）。与安慰剂相比，阿立哌唑与较低的严重治疗相关不良事件（TEAEs）发生率相关（3.1%比 12.5%；p=0.059）和严重 TEAEs（2.0%比 10.4%；p=0.039）。阿立哌唑的停药率也低于安慰剂（20.4%比 39.6%，p=0.014；危害比=5.1）。与安慰剂相比，阿立哌唑的锥体外系症状、体重增加和嗜睡发生率相似或更低，且未报告与血清催乳素升高相关的 TEAEs。根据 Tanner 分期，接受阿立哌唑治疗的参与者中有 27.6%和接受安慰剂的参与者中有 16.7%从基线进展一个或两个阶段。