Research Institute, Lindner Center of HOPE, Mason, Ohio2Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, Massachusetts.
JAMA Psychiatry. 2015 Mar;72(3):235-46. doi: 10.1001/jamapsychiatry.2014.2162.
Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies.
To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED.
DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively.
Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose.
We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight.
At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis).
The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing.
clinicaltrials.gov Identifier: NCT01291173.
暴食障碍（BED）是一种与精神病理症状和肥胖症相关的公共卫生问题，可能与代谢综合征有关，目前尚无批准的药物治疗方法。
研究右苯丙胺前体 lisdexamfetamine dimesylate 治疗中重度 BED 的疗效和安全性。
设计、地点和参与者：我们在 2011 年 5 月 10 日至 2012 年 1 月 30 日期间在 30 个地点进行了一项随机、双盲、平行组、强制剂量滴定、安慰剂对照临床试验。安全性和意向治疗分析分别纳入了 259 名和 255 名 BED 成年患者。
研究参与者分别接受 30、50 或 70mg/d 的 lisdexamfetamine dimesylate 或安慰剂治疗（1:1:1:1）。剂量在 3 周内滴定，并维持 8 周。我们在最后一次给药后平均（SD）7（2）天对参与者进行随访。
采用混合效应模型，使用转化的对数（每周暴食天数）+1 评估暴食行为的变化（基线至第 11 周）。次要指标包括 4 周的暴食停止。安全性评估包括治疗中出现的不良事件、生命体征和体重变化。
在第 11 周，50mg/d（最小二乘[LS]均值[SE]变化，-1.49[0.066]；P=0.008）和 70mg/d（LS 均值[SE]变化，-1.57[0.067]；P<0.001）治疗组的每周暴食天数减少，但 30mg/d 治疗组（LS 均值[SE]变化，-1.24[0.067]；P=0.88）与安慰剂组相比没有减少。安慰剂组和 30、50 和 70mg/d 治疗组的非转化平均（SD）每周暴食天数分别减少 3.3（2.04）、3.5（1.95）、4.1（1.52）和 4.1（1.57）。安慰剂组的 4 周暴食停止率为 21.3%，低于 50mg/d（42.2%[P=0.01]）和 70mg/d（50.0%[P<0.001]）治疗组。任何治疗中出现的不良事件发生率在安慰剂组为 58.7%，在联合治疗组为 84.7%。在治疗组中，1.5%的参与者出现严重的治疗中出现的不良事件。频率至少为 5%的事件和心率变化通常与已知的安全性特征一致。安慰剂组、30、50 和 70mg/d 治疗组以及联合治疗组的体重平均（SD）变化分别为-0.1（3.09）、-3.1（3.64）、-4.9（4.43）、-4.9（3.93）和-4.3（4.09）kg（每个剂量与安慰剂组的比较在事后分析中 P<0.001）。
50mg/d 和 70mg/d 治疗组与安慰剂组相比，在减少暴食天数、停止暴食和整体改善方面显示出疗效。安全性特征通常与之前在注意力缺陷/多动障碍成人中发现的一致。目前正在对 Lisdexamfetamine 在 BED 中的应用进行进一步研究。
clinicaltrials.gov 标识符：NCT01291173。
