title: D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical Trial.
abstract: OBJECTIVE
  It is unclear whether d-cycloserine (DCS), a partial N-methyl-d-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD).
  
  
  OBJECTIVE
  To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS.
  
  
  METHODS
  A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population.
  
  
  METHODS
  All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks.
  
  
  METHODS
  Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS.
  
  
  RESULTS
  In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t62 = -3.00; P = .004; and t61 = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups).
  
  
  CONCLUSIONS
  The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01649895.
authors.affiliation: Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden2Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden3Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Hedman
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Enander
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Diana
authors.initials: D
authors.lastname: Radu Djurfeldt
authors.affiliation: Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Brjánn
authors.initials: B
authors.lastname: Ljótsson
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Cervenka
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Josef
authors.initials: J
authors.lastname: Isung
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Svanborg
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Mataix-Cols
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Viktor
authors.initials: V
authors.lastname: Kaldo
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden4Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Lindefors
authors.affiliation: Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Rück
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020407:Internet; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000628:therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013813:Therapy, Computer-Assisted / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine