Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
Department of Psychiatry, University of Cambridge, Cambridge, England3Cambridge and Peterborough NHS Foundation Trust, Cambridge, England.
JAMA Psychiatry. 2016 May 1;73(5):490-6. doi: 10.1001/jamapsychiatry.2016.0060.
Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD.
To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind trial was conducted at ambulatory care centers at the University of Minnesota (September 12, 2011, to June 15, 2012) and the University of Chicago (December 17, 2012, to June 26, 2015) and included 66 adults with SPD. Data analysis was performed from July 16 to September 9, 2015.
N-acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks.
Participants were assessed using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS); total scores range from 0 to 40, with higher scores reflective of greater symptom severity. Another measure of skin-picking severity was the Clinical Global Impression-Severity Scale; total scores range from 1 (normal) to 7 (among the most extremely ill patients), and improvement ratings range from 7 (very much worse) to 1 (very much improved). Selected cognitive tasks included the Intra-dimensional/Extra-dimensional Shift Task to examine cognitive flexibility, with the key outcome measures being the number of errors, and Stop-Signal Reaction Time task, which evaluates motor inhibition. Outcomes were examined using a linear mixed-effects model.
Of the 66 participants (31 randomized to placebo and 35 to N-acetylcysteine) included in the analysis, 59 (89%) were women; mean (SD) age was 34.8 (11.0) years. Compared with placebo, N-acetylcysteine treatment was associated with significant improvements in the NE-YBOCS. At baseline, NE-YBOCS scores were 18.9 and 17.9 for the treatment and placebo groups, respectively, and at 12 weeks, the scores were 11.5 and 14.1 for the treatment and placebo groups, respectively (P = .048). For the Clinical Global Impression-Severity scale, baseline scores were 3.5 and 4.0 and 12-week scores were 3.0 and 4.2, respectively (P = .003). These effects were significant both in terms of treatment by time interactions and post hoc tests at 1 or more individual time points. At the study's end point, of the 53 participants who completed the study, 15 of the 32 participants (47%) receiving N-acetylcysteine were much or very much improved compared with 4 of the 21 participants (19%) receiving placebo (P = .03). There were no significant differences between the active and placebo arms in terms of psychosocial functioning.
N-acetylcysteine treatment resulted in significant reductions in skin-picking symptoms and was well tolerated. The glutamate system may prove a beneficial target in treating SPD and other compulsive behaviors.
clinicaltrials.gov Identifier: NCT01063348.
Excoriation(皮肤搔抓)障碍(SPD)是一种使人衰弱且未被充分认识的疾病,个体反复搔抓皮肤,导致明显的组织损伤。迄今为止,尚无明确有效的药物或心理治疗 SPD。
确定 N-乙酰半胱氨酸是否比安慰剂更有效,N-乙酰半胱氨酸是一种似乎可以恢复伏隔核细胞外谷氨酸浓度的氨基酸,可减少强制性抓挠行为。
设计、地点和参与者:一项随机、双盲试验于 2011 年 9 月 12 日至 2012 年 6 月 15 日在明尼苏达大学的门诊中心和 2012 年 12 月 17 日至 2015 年 6 月 26 日在芝加哥大学进行,纳入了 66 名 SPD 成年人。数据分析于 2015 年 7 月 16 日至 9 月 9 日进行。
N-乙酰半胱氨酸(剂量范围 1200-3000mg/d)或安慰剂治疗 12 周。
参与者使用改良耶鲁-布朗强迫症量表(NE-YBOCS)等皮肤搔抓严重程度评估方法进行评估;总分为 0 到 40 分,得分越高表示症状越严重。另一种皮肤搔抓严重程度的评估方法是临床总体印象严重程度量表;总分为 1(正常)到 7(最严重的患者),改善评分范围为 7(明显恶化)到 1(明显改善)。选择的认知任务包括内-外维度转移任务,以检查认知灵活性,关键的结果测量是错误的数量,以及停止信号反应时间任务,评估运动抑制。使用线性混合效应模型检查结果。
在纳入分析的 66 名参与者(31 名随机分配到安慰剂组和 35 名分配到 N-乙酰半胱氨酸组)中,59 名(89%)为女性;平均(SD)年龄为 34.8(11.0)岁。与安慰剂相比,N-乙酰半胱氨酸治疗与 NE-YBOCS 的显著改善相关。基线时,治疗组和安慰剂组的 NE-YBOCS 评分分别为 18.9 和 17.9,治疗 12 周后,评分分别为 11.5 和 14.1,治疗组和安慰剂组(P = .048)。对于临床总体印象严重程度量表,基线评分分别为 3.5 和 4.0,12 周评分分别为 3.0 和 4.2(P = .003)。这些效果在治疗时间相互作用和 1 个或多个时间点的事后检验中均具有统计学意义。在研究结束时,53 名完成研究的参与者中,32 名接受 N-乙酰半胱氨酸治疗的参与者中有 15 名(47%)得到了很大或非常大的改善,而 21 名接受安慰剂治疗的参与者中只有 4 名(19%)(P = .03)。在社会心理功能方面,活性药物组和安慰剂组之间没有显著差异。
N-乙酰半胱氨酸治疗可显著减少搔抓症状,且耐受性良好。谷氨酸系统可能是治疗 SPD 和其他强迫行为的有益靶点。
clinicaltrials.gov 标识符:NCT01063348。