Enhancement of psychosocial treatment with D-cycloserine: Models, moderators, and future directions
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Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).
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The benefit of DCS-augmented EBT seems to be reduced in patients receiving antidepressants.
“Furthermore, the benefit of DCS-augmented EBT seems to be reduced in patients receiving antidepressants (King et al., 2018;Otto et al., 2016).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Otto et al., 2016
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Bolkan, S. S., & Lattal, K. M. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.12.009 · Cited by 26 · see citing works
Stopping Anxiety Medication Therapist Guide
Otto, M. W., & Pollack, M. H. (2009) · Oxford University Press eBooks · doi:10.1093/med:psych/9780195338546.001.0001 · Cited by 7 · see citing works
Self-citationD-Cycloserine for Treatment Nonresponders With Obsessive-Compulsive Disorder: A Case Report
Norberg, M. M., Gilliam, C. M., Villavicencio, A. L., Pearlson, G. D., & Tolin, D. F. (2011) · Cognitive and Behavioral Practice · doi:10.1016/j.cbpra.2011.05.002 · Cited by 5 · see citing works
Self-citation
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Research works printed but not linked: 1
- [88]Chasson GS Buhlmann U Tolin DF Rao SR Reese HE Rowley T 2010 Need for speed: evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine Behav Res Ther 48 675 9 20362975
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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
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The Lancet Psychiatry Commission on psychological treatments research in tomorrow's science
Holmes, E. A., Ghaderi, A., Harmer, C. J., Ramchandani, P. G., Cuijpers, P., Morrison, A. P., Roiser, J. P., Bockting, C. L. H., O'Connor, R. C., Shafran, R., et al. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30513-8 · Cited by 624 · see citing works
Mataix-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 · see citing works
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McGuire, J. F., Orr, S. P., Essoe, J. K.-Y., McCracken, J. T., Storch, E. A., & Piacentini, J. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1199276 · Cited by 67 · see citing works
“Additional research is needed to better understand the nuances of augmenting CBT with cognitive enhancers in youth [24,25].”
Rosencrans, P. L., Bui, E., Rogers, A. H., Simon, N. M., & Baker, A. W. (2017) · International Journal of Cognitive Therapy · doi:10.1521/ijct.2017.10.4.283 · Cited by 12 · see citing works
Smits, J. A. J., Zvolensky, M. J., Otto, M. W., Piper, M. E., Baird, S. O., Kauffman, B. Y., Lee-Furman, E., Alavi, N., Dutcher, C. D., Papini, S., et al. (2020) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2020.107877 · Cited by 5 · see citing works
Self-citationNew pharmacological strategies for augmenting extinction learning in anxiety disorders
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- Authors
- Otto, M. W., Kredlow, M. A., Smits, J. A. J., Hofmann, S. G., Tolin, D. F., de Kleine, R. A., van Minnen, A., Evins, A. E., & Pollack, M. H.
- Affiliations
- Boston University (US)
- The University of Texas at Austin (US)
- Harvard University (US)
- Rush University Medical Center (US)
- Corresponding author
- Otto, Michael W.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 80
- Issue
- 4
- Pages
- 274-283
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4808479
- OpenAlex
- W1780722919
- Cited by
- 70
- References
- 89
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 12 · 2019: 11 · 2018: 11 · 2017: 16 · 2016: 7
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OpenBU (Boston University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institutes of Health (NIH)/National Institute of Mental Health (R21MH102646)
- NIH/NIMH (1F31MH103969, R34MH099318, R34MH086668, 5R34MH099309-02)
- NIDA (Grant No. K24 DA030443)
- 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 › Posttraumatic Stress Disorder Research
- Keywords
- D-cycloserine, exposure therapy, fear extinction, anxiety disorders, NMDA receptor agonist, augmentation therapy, hippocampus-dependent learning, addiction treatment, anorexia nervosa, schizophrenia, depression
- MeSH terms
- Antimetabolites, Anxiety Disorders, Combined Modality Therapy, Cycloserine, Extinction, Psychological, Humans, Implosive Therapy
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