Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder
Abstract
Background Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders. Enhancement of cognitive-behavior therapy with d-cycloserine (DCS) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder.Method This is a randomized, double-blind, placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy. Randomized participants were 31 outpatients meeting DSM-IV criteria for panic disorder with or without agoraphobia, who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations (interoceptive exposure) but also including informational, cognitive, and situational exposure interventions. Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5. The primary outcome measures were the Panic Disorder Severity Scale (PDSS) and Clinicians' Global Impressions of Severity.Results Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder. At posttreatment and 1 month follow-up, participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinically significant change status (77% vs. 33%). There were no significant adverse effects associated with DCS administration.Conclusions This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder.
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Our data, together with prior studies, form a pattern of evidence supporting that DCS may facilitate extinction learning.
“Our data, in conjunction with that of Ressler et al (2004), Hofmann et al (2006), and Otto et al (2010), form a compelling pattern of evidence supporting the hypothesis that DCS may facilitate extinction learning.”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Otto et al, 2010
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- Authors
- Otto, M. W., Tolin, D. F., Simon, N. M., Pearlson, G. D., Basden, S., Meunier, S. A., Hofmann, S. G., Eisenmenger, K., Krystal, J. H., & Pollack, M. H.
- Affiliations
- Boston University (US)
- Hartford Hospital (US)
- Harvard University (US)
- Yale University (US)
- Corresponding author
- Otto, Michael W.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 67
- Issue
- 4
- Pages
- 365-370
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2071586792
- Cited by
- 251
- References
- 37
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 10 · 2018: 15 · 2017: 17 · 2016: 14 · 2015: 20 · 2014: 36 · 2013: 32 · 2012: 27
- FWCI
- 32.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- D-cycloserine, panic disorder, cognitive behavioral therapy, augmentation therapy, interoceptive exposure, agoraphobia, fear extinction
- MeSH terms
- Adult, Analysis of Variance, Antimetabolites, Cycloserine, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Severity of Illness Index, Cognitive Behavioral Therapy, Panic Disorder, Young Adult
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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