title: N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  N-acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01063348.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Grant
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, England3Cambridge and Peterborough NHS Foundation Trust, Cambridge, England.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Chamberlain
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Redden
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Leppink
authors.affiliation: Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Odlaug
authors.affiliation: Department of Psychiatry, University of Minnesota Medical School, Minneapolis.
authors.forename: Suck Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016728:Self-Injurious Behavior / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D012867:Skin / Q000293:injuries*; D055815:Young Adult
chemical_list: D018698:Glutamic Acid; D000111:Acetylcysteine