The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
d-cycloserine enhancement of exposure therapy for social anxiety disorder depends on the success of exposure sessions
Open accessAbstract
Objective The evidence for the efficacy of D-cycloserine (DCS) for augmenting cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided by preclinical research and initial findings from a small-scale study involving humans, we tested the hypothesis that DCS enhancement of exposure therapy would be specific to successful exposure sessions. Method Medication-free adults with generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1 h before each of 5 exposure sessions that were part of a standardized 12-session group CBT protocol. Participants provided fear ratings at the beginning and just before the end of exposure exercises. Independent raters, blind to group assignment, administered the clinical global impression improvement and severity scales at each session and at posttreatment. Results Mixed-effects analyses revealed that, among patients who reported low fear at the end of an exposure session, those who had received DCS evidenced significantly greater clinical improvement at the next session, relative to those who had received placebo. In contrast, when exposure end fear was high, patients receiving DCS exhibited less clinical improvement at the following session than patients receiving placebo. Similarly, patients who had received DCS evidenced lower clinical severity at posttreatment, relative to patients who had received placebo, only when their average end fear for medication-augmented sessions had been in the low to moderate range. Finally, these moderating effects of exposure success as indexed by end fear were not better accounted for by within-session extinction. Conclusions The efficacy of DCS for augmenting exposure-based CBT depends on the success of exposure sessions. These findings may help guide the development of an algorithm for the effective use of DCS for augmenting exposure-based CBT. Trial registry http://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/NCT00633984.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“administration of the NMDAR partial agonist D-cycloserine (DCS) enhances the acquisition of the extinction memory”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Smits et al., 2013
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Multiple regression: testing and interpreting interactions
(1992) · Choice Reviews Online · doi:10.5860/choice.29-3352 · Cited by 36,647
Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.617 · Cited by 12,052 · cited 2×
“All rights reserved. http://dx.doi.org/10.1016/j.jpsychires.2013.06.020 such as social anxiety disorder (Hofmann and Smits, 2008), which are prevalent and associated with significant personal and economic costs (Greenberg et al., 1999; Kessler et al., 2005).”
BackgroundInfluentialPsychotherapy by reciprocal inhibition
Wolpe, J. (1968) · Pavlovian Journal of Biological Science · doi:10.1007/bf03000093 · Cited by 3,406
Psychotherapy by Reciprocal Inhibition
Masserman, J. H. (1958) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1958.02340090135025 · Cited by 3,087
Liebowitz, M. R. (2015) · Modern Trends in Pharmacopsychiatry · doi:10.1159/000414022 · Cited by 2,266
Optimizing inhibitory learning during exposure therapy
Craske, M. G., Kircanski, K., Zelikowsky, M., Mystkowski, J., Chowdhury, N., & Baker, A. (2008) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.10.003 · Cited by 1,607
Guy, W. L. (2025) · Springer Reference Medizin · doi:10.1007/978-3-662-65186-5_300379 · Cited by 1,441
Hoffman, S. G., & Smits, J. A. J. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0415 · Cited by 1,420
Self-citationThe economic burden of anxiety disorders in the 1990s
Greenberg, P. E., Sisitsky, T., Kessler, R. C., Finkelstein, S. N., Berndt, E. R., Davidson, J. R. T., Ballenger, J. C., & Fyer, A. J. (1999) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v60n0702 · Cited by 1,242 · cited 2×
“All rights reserved. http://dx.doi.org/10.1016/j.jpsychires.2013.06.020 such as social anxiety disorder (Hofmann and Smits, 2008), which are prevalent and associated with significant personal and economic costs (Greenberg et al., 1999; Kessler et al., 2005).”
BackgroundInfluentialHofmann, S. G. (2007) · Cognitive Behaviour Therapy · doi:10.1080/16506070701421313 · Cited by 1,064 · cited 1×
“The intervention approach was based on a 12-week CBT treatment protocol involving weekly 2.5-h sessions (Heimberg and Becker, 2002), but drew heavily from the strategies outlined by Hofmann and Otto (Hofmann and Otto, 2008) based on the model described by Hofmann (2007).”
MethodInfluentialSelf-citationRessler, K. J., Rothbaum, B. O., Tannenbaum, L., Anderson, P., Graap, K., Zimand, E., Hodges, L., & Davis, M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.11.1136 · Cited by 1,063 · cited 1×
“…across these studies, with several evidencing strong augmentative effects of DCS (Guastella et al., 2008; Hofmann et al., 2006; Otto et al., 2010; Ressler et al., 2004), and several showing either relatively weak effects (Kushner et al., 2007; Wilhelm et al., 2008), no effects (Guastella et al.,…”
BackgroundSelf-citationAugmentation of Exposure Therapy With D-Cycloserine for Social Anxiety Disorder
Hofmann, S. G., Meuret, A. E., Smits, J. A. J., Simon, N. M., Pollack, M. H., Eisenmenger, K., Shiekh, M., & Otto, M. W. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.3.298 · Cited by 560 · cited 3×
“The efficacy of D-cycloserine (DCS) for enhancing exposure therapy has been variable across these studies, with several evidencing strong augmentative effects of DCS (Guastella et al., 2008; Hofmann et al., 2006; Otto et al., 2010; Ressler et al., 2004), and several showing either relatively weak effects (Kushner et a…”
BackgroundResultSelf-citationEffects of D-Cycloserine on Extinction: Translation From Preclinical to Clinical Work
Davis, M., Ressler, K., Rothbaum, B. O., & Richardson, R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.084 · Cited by 498 · cited 3×
“…research is the investigation of D-cycloserine (DCS), a partial agonist of the glycine recognition site of the N-Methyl-D-Aspartate receptor (NMDAr), as an augmentation strategy for exposure-based cognitive behavioral therapy for the anxiety disorders (Davis et al., 2006; Hofmann et al., 2011).”
BackgroundInfluentialSelf-citationReconsolidation and Extinction of Conditioned Fear: Inhibition and Potentiation
Lee, J. L. C., Milton, A. L., & Everitt, B. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2466-06.2006 · Cited by 479 · cited 2×
“Assuming clinicians accurately targeted patients’ fears with challenging exposure assignments, low end fear provides a measure of extinction success, consistent with preclinical studies (Lee et al., 2006).”
ResultPhenelzine vs Atenolol in Social Phobia: A Placebo-Controlled Comparison
Liebowitz, M. R., Schneier, F., Campeas, R., Hollander, E., Hatterer, J., Fyer, A., Gorman, J., Papp, L., Davies, S., Gully, R., et al. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.49.4.290 · Cited by 444 · cited 1×
“Randomization was performed in a double-blind fashion using a computer-generated allocation schedule which stratified participants by baseline LSAS severity ratings ( 70 or 70; Liebowitz et al., 1992).”
Method(2002) · Cited by 399
D-Cycloserine Augmented Exposure Therapy for Obsessive-Compulsive Disorder
Kushner, M. G., Kim, S. W., Donahue, C. B., THURAS, P. D., Adson, D. E., Kotlyar, M., McCabe, J., Peterson, J., & Foa, E. B. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.12.020 · Cited by 384 · cited 2×
“, 2004), and several showing either relatively weak effects (Kushner et al., 2007; Wilhelm et al., 2008), no effects (Guastella et al.”
BackgroundAugmentation of Behavior Therapy With d -Cycloserine for Obsessive-Compulsive Disorder
Wilhelm, S., Buhlmann, U., Tolin, D. F., Meunier, S. A., Pearlson, G. D., Reese, H. E., Cannistraro, P., Jenike, M. A., & Rauch, S. L. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07050776 · Cited by 358 · cited 2×
“, 2004), and several showing either relatively weak effects (Kushner et al., 2007; Wilhelm et al., 2008), no effects (Guastella et al.”
BackgroundCognitive mediation of treatment change in social phobia
Hofmann, S. G. (2004) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.72.3.392 · Cited by 348 · cited 1×
“This is similar to previous studies from our group (e.g., Hofmann, 2004; Hofmann et al.2006), which have shown”
ResultSelf-citationGoldin, P. R., Ziv, M., Jazaieri, H., Werner, K., Kraemer, H., Heimberg, R. G., & Gross, J. J. (2012) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0028555 · Cited by 332 · cited 1×
“Among other therapeutic change processes that are potentially important to exposure therapy outcome, increased implementation of emotion regulation strategies such as cognitive reappraisal may be important to consider in future studies that aim to enhance the understanding of why DCS may only exert positive effects wh…”
BackgroundGuastella, A. J., Richardson, R., Lovibond, P. F., Rapee, R. M., Gaston, J. E., Mitchell, P., & Dadds, M. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.11.011 · Cited by 326 · cited 1×
“…(DCS) for enhancing exposure therapy has been variable across these studies, with several evidencing strong augmentative effects of DCS (Guastella et al., 2008; Hofmann et al., 2006; Otto et al., 2010; Ressler et al., 2004), and several showing either relatively weak effects (Kushner…”
BackgroundEfficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder
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. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.036 · Cited by 251
Self-citationLast observation carried forward versus mixed models in the analysis of psychiatric clinical trials.
Hamer, R. M., & Simpson, P. M. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09040458 · Cited by 233
D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder
Storch, E. A., Merlo, L. J., Bengtson, M., Murphy, T. K., Lewis, M. H., Yang, M. C., Jacob, M. L., Larson, M., Hirsh, A., Fernandez, M., et al. (2007) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32819f8480 · Cited by 200 · cited 1×
“…al., 2008; Hofmann et al., 2006; Otto et al., 2010; Ressler et al., 2004), and several showing either relatively weak effects (Kushner et al., 2007; Wilhelm et al., 2008), no effects (Guastella et al., 2007; Storch et al., 2007; Tart et al., 2013), or even detrimental effects (Litz et al., 2012).”
BackgroundLitz, B. T., Salters-Pedneault, K., Steenkamp, M. M., Hermos, J. A., Bryant, R. A., Otto, M. W., & Hofmann, S. G. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.05.006 · Cited by 196 · cited 2×
“, 2013), or even detrimental effects (Litz et al., 2012).”
BackgroundSelf-citationA randomized controlled trial of the effect of D-cycloserine on exposure therapy for spider fear
Guastella, A. J., Dadds, M. R., Lovibond, P. F., Mitchell, P., & Richardson, R. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.05.006 · Cited by 164 · cited 2×
“, 2008), no effects (Guastella et al., 2007; Storch et al., 2007; Tart et al., 2013), or even detrimental effects (Litz et al.”
BackgroundSmits, J. A. J., Julian, K., Rosenfield, D., & Powers, M. B. (2012) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0028957 · Cited by 162 · cited 1×
“Among other therapeutic change processes that are potentially important to exposure therapy outcome, increased implementation of emotion regulation strategies such as cognitive reappraisal may be important to consider in future studies that aim to enhance the understanding of why DCS may only exert positive effects wh…”
BackgroundSelf-citationSmits, J. A. J., Rosenfield, D., Otto, M. W., Powers, M. B., Hofmann, S. G., Telch, M. J., Pollack, M. H., & Tart, C. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.009 · Cited by 142 · cited 4×
“…study (Smits et al., 2013b), we also explored in this paper the possibility that within- session extinction (i.e., peak fear minus end fear), an alternative operationalization of exposure success (Smits et al., 2013b), is a more critical dimension formoderating the efficacy of DCS than end fear.”
BackgroundMethodInfluentialSelf-citationCognitive mechanisms of social anxiety reduction: an examination of specificity and temporality
Smits, J. A. J., Rosenfield, D., McDonald, R., & Telch, M. J. (2006) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.74.6.1203 · Cited by 138
Self-citationHofmann, 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. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12070974 · Cited by 121 · cited 6×
“This is similar to previous studies from our group (e.g., Hofmann, 2004; Hofmann et al.2006), which have shown”
BackgroundInfluentialSelf-citationD-cycloserine facilitates context-specific fear extinction learning
Bouton, M. E., Vurbic, D., & Woods, A. M. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.07.003 · Cited by 118 · cited 2×
“Consistent with the findings from animal studies (Bouton et al., 2008;Weber et al., 2007), the result of this reanalysis showed that DCS facilitated clinical improvement when patients ended their previous exposure session with low fear levels, and, conversely, inhibited clinical improvement when…”
MethodResultCook, T. D., & Steiner, P. M. (2010) · Psychological Methods · doi:10.1037/a0018536 · Cited by 117
Cognitive Behavioral Therapy for Social Anxiety Disorder
Hofmann, S. G., & Otto, M. W. (2017) · Routledge eBooks · doi:10.4324/9781315617039 · Cited by 111
Self-citationEffects of D-cycloserine on extinction of learned fear to an olfactory cue
Weber, M., Hart, J., & Richardson, R. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2006.12.010 · Cited by 83
Augmentation of exposure therapy with post-session administration of D-cycloserine
Tart, C. D., Handelsman, P. R., DeBoer, L. B., Rosenfield, D., Pollack, M. H., Hofmann, S. G., Powers, M. B., Otto, M. W., & Smits, J. A. J. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.024 · Cited by 75 · cited 2×
“The original analyses revealed that patients receiving 50 mg of DCS administered following each of two sessions of 30 min of hierarchical virtual reality exposure did not evidence better clinical outcomes than patients receiving identical exposure combined with placebo (Tart et al., 2013).”
BackgroundInfluentialSelf-citationSmits, J. A. J., Powers, M. B., Buxkamper, R., & Telch, M. J. (2006) · Behaviour Research and Therapy · doi:10.1016/j.brat.2006.01.001 · Cited by 72
Self-citationCognitive enhancers for anxiety disorders
Hofmann, S. G., Smits, J. A. J., Asnaani, A., Gutner, C. A., & Otto, M. W. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.11.020 · Cited by 69 · cited 10×
“These findings may help guide the development of an algorithm for the effective use of DCS for augmenting exposure-based CBT. Trial registry: http://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/ NCT00633984.”
BackgroundInfluentialSelf-citationDoes fear reactivity during exposure predict panic symptom reduction?
Meuret, A. E., Seidel, A., Rosenfield, B., Hofmann, S. G., & Rosenfield, D. (2012) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0028032 · Cited by 67
Self-citationSmits, J. A. J., Hofmann, S. G., Rosenfield, D., Hopkins, L. B., Costa, P. T., Simon, N. M., O’Cleirigh, C. M., Meuret, A. E., Marques, L. M., Otto, M. W., et al. (2013) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0034120 · Cited by 46 · cited 5×
“In our reanalysis of these findings (Smits et al., 2013b), we tested whether the effects of DCS administration on subsequent clinical improvement would be moderated by the relative success of the exposure session.”
BackgroundMethodInfluentialSelf-citationExtinction retention predicts improvement in social anxiety symptoms following exposure therapy
Berry, A. C., Rosenfield, D., & Smits, J. A. J. (2008) · Depression and Anxiety · doi:10.1002/da.20511 · Cited by 40
Self-citationHayes, S. A., Hope, D. A., & Heimberg, R. G. (2008) · Behavior Therapy · doi:10.1016/j.beth.2007.09.001 · Cited by 39
Cited by
Sorted by citations
Lonsdorf, T. B., Menz, M. M., Andreatta, M., Fullana, M. A., Golkar, A., Haaker, J., Heitland, I., Hermann, A., Kuhn, M., Kruse, O., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.02.026 · Cited by 837
“…and exposure treatment were only observed in animals (Bolkan and Lattal, 2014; Bouton et al., 2008; Weber et al., 2007) and humans who did demonstrate successful extinction learning/treatment response to cognitive-behavioural therapy (CBT) (Smits et al., 2013a, 2013b, 2014; Telch et al., 2014).”
Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390
“…phobia (Guastella et al., 2007; Nave et al., 2012; Ressler et al., 2004), SAD (Guastella et al., 2008; Hofmann et al., 2006; Hofmann et al., 2013b; Smits et al., 2013c) and OCD [(Chasson et al., 2010; Farrell et al., 2013; Kushner et al., 2007; Storch et al., 2010; Wilhelm et al., 2008) but see…”
BackgroundMethodInfluentialRothbaum, B. O., Price, M., Jovanovic, T., Norrholm, S. D., Gerardi, M., Dunlop, B., Davis, M., Bradley, B., Duncan, E. J., Rizzo, A., et al. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121625 · Cited by 388
“conditions, is consistent with the increasing evidence that d-cycloserine’s clinical effect may be best observed through enhancing consolidation of extinction gains made between sessions (10, 14, 24, 25, 35) and preventing return of symptoms after treatment.”
BackgroundResultSelf-citationMataix-Cols, D., Fernández de la Cruz, L., Monzani, B., Rosenfield, D., Andersson, E., Pérez-Vigil, A., Frumento, P., de Kleine, R. A., Difede, J., Dunlop, B. W., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.3955 · Cited by 288
“inadvertently interfered with exposure efficacy in some patients and facilitated its efficacy in others.(57,58)”
Self-citationThe subjective experience of emotion: a fearful view
LeDoux, J. E., & Hofmann, S. G. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.09.011 · Cited by 268
Self-citation
Metadata
- Authors
- Smits, J. A. J., Rosenfield, D., Otto, M. W., Marques, L., Davis, M. L., Meuret, A. E., Simon, N. M., Pollack, M. H., & Hofmann, S. G.
- Affiliations
- Southern Methodist University (US)
- Boston University (US)
- Massachusetts General Hospital (US)
- Rush University Medical Center (US)
- Corresponding author
- Hofmann, Stefan G.
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 47
- Issue
- 10
- Pages
- 1455-1461
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC3747985
- OpenAlex
- W2157504515
- Cited by
- 114
- References
- 41
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 17 · 2017: 15 · 2016: 9 · 2015: 19 · 2014: 14 · 2013: 3
- FWCI
- 20.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH075889, K23MH096029, R01MH078308)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- D-cycloserine, social anxiety disorder, exposure therapy, cognitive behavioral therapy, drug augmentation, treatment response, treatment algorithm
- MeSH terms
- Adult, Antidepressive Agents, Anxiety Disorders, Cycloserine, Double-Blind Method, Fear, Female, Humans, Implosive Therapy, Male, Severity of Illness Index, Models, Statistical, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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 ›
Are you an author, or do you see a problem with this page? Request a review
