d-Cycloserine as an Augmentation Strategy With Cognitive-Behavioral Therapy for Social Anxiety Disorder
Open accessAbstract
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.
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This study's results are consistent with previous research and meta-analyses showing that CBT is effective for social anxiety disorder.
“This study aligns with previous research about the efficacy of CBT on SAD symptoms.”
From Trial-Based Cognitive Therapy: Efficacy of a New CBT Approach for Treating Social Anxiety Disorder with Comorbid Depression. (2018) · cites this paper as Hofmann et al. 2013
The Discussion reports response rates above 70% in both CBT groups and cites earlier CBT trials with response rates of 50.8% and 47.1%, supporting the stated alignment with previous research on CBT for social anxiety disorder. The passage does not report a meta-analysis, so that additional part of the paraphrased claim is not supported by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredNull effects of D-cycloserine during exposure in vivo for SAD have also been reported.
“although null effects have also been reported (Hofmann et al., 2013).”
From Virtual Reality exposure therapy in the treatment of public speaking anxiety and social anxiety disorder (2024) · cites this paper as Hofmann et al., 2013
Fluvoxamine was found to be well tolerated and short-time effective for anxiety disorders.
“Fluvoxamine was found to be well tolerated and short-time effective for anxiety disorders.”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [39]
The Introduction discusses anxiolytic drugs such as paroxetine, fluoxetine, and phenelzine, while the Methods describe a trial of d-cycloserine with cognitive-behavioral therapy. Searches for fluvoxamine and for short-term efficacy and tolerability found no passage addressing the claim about fluvoxamine. (LLM, conf=0.76)
Experimental — accuracy not yet measuredFluvoxamine has potential risks such as cognitive impairment, disinhibition, depression and dependence.
“Despite the described benefits, the authors raise awareness of its potential risks such as cognitive impairment, disinhibition, depression and dependence.”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [39]
The Introduction discusses d-cycloserine and names other anxiety medications, but does not discuss fluvoxamine. Searches for fluvoxamine and the specified risks found no passage linking cognitive impairment, disinhibition, depression, or dependence to fluvoxamine in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredDCS administration before or after exposure therapy was effective in alleviating symptoms of acrophobia, panic disorder, social anxiety disorder, and obsessive-compulsive disorder.
“Shortly thereafter, several groups reported that DCS administration before or after exposure therapy, a form of treatment based on the principles of fear extinction learning, was effective in alleviating the symptoms of acrophobia (67), panic disorder (68), social anxiety disorder (69, 70), and obsessive–compulsive disorder (71–73).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [70]
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Self-citationd-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders
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D-CYCLOSERINE ENHANCES GENERALIZATION OF FEAR EXTINCTION IN CHILDREN
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“For SAD, early studies on D-cycloserine administration during exposure in vivo have yielded promising results (Guastella et al., 2008; Hofmann et al., 2006; Rodrigues et al., 2014), although null effects have also been reported (Hofmann et al., 2013).”
Psychological treatment of social anxiety disorder improves body dysmorphic concerns
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- Authors
- Hofmann, S. G., Smits, J. A. J., Rosenfield, D., Simon, N., Otto, M. W., Meuret, A. E., Marques, L., Fang, A., Tart, C., & Pollack, M. H.
- Affiliations
- Boston University (US)
- Corresponding author
- Hofmann, Stefan G.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2013-07
- Volume
- 170
- Issue
- 7
- Pages
- 751-758
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4058999
- OpenAlex
- W2169145652
- Cited by
- 121
- References
- 40
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 9 · 2019: 5 · 2018: 15 · 2017: 11 · 2016: 10 · 2015: 22 · 2014: 20 · 2013: 10
- FWCI
- 27.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH075889, K23MH096029, R01MH078308)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- D-cycloserine, social anxiety disorder, generalized anxiety disorder, cognitive behavioral therapy, augmentation therapy, NMDA receptor partial agonist, exposure therapy, treatment response and remission
- MeSH terms
- Adult, Combined Modality Therapy, Cycloserine, Female, Humans, Interview, Psychological, Male, Phobic Disorders, Psychiatric Status Rating Scales, Remission Induction, Cognitive Behavioral Therapy, Receptors, N-Methyl-D-Aspartate
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