Importance  The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important.

Objective  To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder.

Design, Setting, and Participants  A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions−Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase.

Interventions  Lisdexamfetamine administration.

Main Outcomes and Measures  The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events.

Results  Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ²₁, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine.

Conclusions and Relevance  Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo.

Trial Registration  clinicaltrials.gov Identifier: NCT02009163

重要性  精神疗法中长期治疗的药物疗法预防复发并保持疗效的能力很重要。

目的  评估赖斯地非乙胺二甲磺酸盐在中度至重度暴食症患者中的疗效。

设计，背景和参与者  从2014年1月27日至2015年4月8日，在49个临床研究地点进行了包括418名参与者的跨国，三阶段，双盲，安慰剂对照的随机退出研究。符合条件的成年人参加了DSM -IV-R暴饮暴食标准，并有中度至重度暴饮暴食症（在开放标签基准之前的14天中，每周暴饮暴食≥3天，连续14天；筛查时临床总体印象-严重程度[CGI-S]得分≥4[中等严重程度]和开放标签基准）。经过12周的开放标签阶段（剂量优化，为4周[赖斯地非胺二甲磺酸盐，50或70 mg]；维持剂量为8周），赖斯地尔非敏反应（每周≤1暴饮暴食，连续4周，CGI-在第26周，双盲，随机停药阶段，将12周的S分数≤2）随机分配给安慰剂或续用赖氨苯丙胺。

干预措施  右旋苯丙胺给药。

主要结果和衡量指标  主要结果变量，即复发时间（连续2周每周≥2暴饮暴食日，连续抽提基线较≥2点CGI-S得分增加），采用对数秩检验（初步分析）；根据两周戒断状态分为两类，进行了分层分析。安全性评估包括治疗紧急不良事件。

结果  在开放标签研究的418名参与者中，有411名（358名[87.1％]妇女；平均[SD]年龄为38.3 [10.4]岁）被纳入安全性分析集。在275名随机分组的lisdexamfetamine应答者（安慰剂，n = 138； lisdexamfetamine，n = 137）中，观察到的达到复发标准的参与者为lisdexamfetamine的比例为3.7％（136个中的5个），安慰剂为32.1％（131个中的42个）。赖氨酸安非他命证明优于对数秩检验（安慰剂χ ² ₁，40.37; P <.001）的复发时间；基于赖氨酸安非他明与安慰剂的Cox比例风险模型，风险比为0.09（95％CI，0.04-0.23）。观察到的治疗中出现的不良事件通常与赖氨苯丙胺的已知特征相符。

结论与相关性  连续进行赖斯地非胺治疗的参与者连续6个月暴饮暴食复发的风险要低于随机接受安慰剂的参与者。赖氨酸安非他明复发的危险性低于安慰剂。

试验注册  临床试验.gov标识符：NCT02009163