D-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder

Am J Psychiatry. 2013 Jul;170(7):751-8. doi: 10.1176/appi.ajp.2013.12070974.


Objective: The authors examined whether D-cycloserine, a partial agonist at the glutamatergic N-methyl-d-aspartate receptor, augments and accelerates a full course of comprehensive cognitive-behavioral therapy (CBT) in adults with generalized social anxiety disorder.

Method: This was a multisite randomized placebo-controlled efficacy study with 169 medication-free adults with generalized social anxiety disorder, of whom 144 completed the 12-week treatment and 131 completed the three follow-up assessments. Patients were randomly assigned to receive 50 mg of D-cycloserine or placebo 1 hour before each of five exposure sessions that were part of a 12-session cognitive-behavioral group treatment. Response and remission status was determined at baseline, throughout treatment, at end of treatment, and at 1-, 3-, and 6-month follow-up assessments by assessors who were blind to treatment condition.

Results: D-Cycloserine-augmented and placebo-augmented CBT were associated with similar completion rates (87% and 82%), response rates (79.3% and 73.3%), and remission rates (34.5% and 24.4%) at the posttreatment assessment; response and remission rates were largely maintained at the follow-up assessments. Although D-cycloserine was associated with a 24%-33% faster rate of improvement in symptom severity and remission rates relative to placebo during the treatment phase, the groups did not differ in response and remission rates.

Conclusions: D-Cycloserine did not augment a full course of comprehensive CBT for social anxiety disorder.

Trial registration: ClinicalTrials.gov NCT00633984.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Cycloserine / therapeutic use*
  • Female
  • Humans
  • Interview, Psychological
  • Male
  • Phobic Disorders / drug therapy
  • Phobic Disorders / therapy*
  • Psychiatric Status Rating Scales
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Remission Induction


  • Receptors, N-Methyl-D-Aspartate
  • Cycloserine

Associated data

  • ClinicalTrials.gov/NCT00633984