Augmentation of exposure therapy with post-session administration of D-cycloserine
Open accessAbstract
Background Pre-session administration of d-cycloserine (DCS) has been found to augment exposure therapy outcomes in a variety of anxiety disorders. To be able to enhance learning only for successful exposure sessions, it would be beneficial to have the option of administering DCS after rather than before the session, a strategy encouraged by pre-clinical work. We believe the present study is the first published report on the efficacy of post-session administration of DCS in humans.Method Adults (N = 29) with a DSM-IV diagnosis of acrophobia were randomized to receive two sessions of virtual reality exposure therapy (VRE) in combination with placebo or 50 mg of DCS. Instead of administering the pill prior to each of the sessions, as has been done in extant work, we administered the pill immediately following each session. Measures of acrophobia severity were collected at baseline, at each treatment session, 1-week post-treatment, and at 1-month follow-up.Results Mixed-effects repeated-measures ANOVAs and GLMMs revealed significant improvement in all outcome measures over time, but no between-group differences were observed. At post-treatment, 63.5% of patients in the placebo condition vs. 60.0% of those in the DCS condition were in remission. At 1-month follow up, 63.4% of those in the placebo condition vs. 66.6% of those in the DCS condition were in remission.Conclusions These findings do not support the application of post-session DCS administration for augmenting the efficacy of exposure-based treatments. Possible reasons for these findings are discussed.Trial registry The Trial is registered at ClinicalTrials.gov (NCT01102803).
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
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?
In the target study, 50 mg DCS administered after each of two sessions of 30 minutes of graded virtual reality exposure did not result in better overall clinical outcomes than identical exposure combined with placebo.
“We found that 50 mg of DCS administered following each of two sessions of 30 minutes of graded virtual reality exposure did not result in better overall clinical outcomes than identical exposure combined with placebo administration (15).”
From D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia (2013) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007) · Behavior Research Methods · doi:10.3758/bf03193146 · Cited by 65,971 · see citing works
Structured Clinical Interview for DSM-IV Axis I Disorders
Spitzer, R. L., First, M. B., & Gibbon, M. (1997) · Medical Entomology and Zoology · Cited by 3,582 · see citing works
Psychotherapy by reciprocal inhibition
Wolpe, J. (1968) · Pavlovian Journal of Biological Science · doi:10.1007/bf03000093 · Cited by 3,389 · see citing works
Psychotherapy by Reciprocal Inhibition
Masserman, J. H. (1958) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1958.02340090135025 · Cited by 3,087 · see citing works
Guy, W. L. (2025) · Springer Reference Medizin · doi:10.1007/978-3-662-65186-5_300379 · Cited by 1,441 · see citing works
Myers, K. M., & Davis, M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001939 · Cited by 1,277 · see citing works
Preventing the return of fear in humans using reconsolidation update mechanisms
Schiller, D., Monfils, M.-H., Raio, C. M., Johnson, D. C., LeDoux, J. E., & Phelps, E. A. (2010) · Nature · doi:10.1038/nature08637 · Cited by 1,248 · see citing works
Ressler, 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 · see citing works
Extinction-Reconsolidation Boundaries: Key to Persistent Attenuation of Fear Memories
Monfils, M.-H., Cowansage, K. K., Klann, E., & LeDoux, J. E. (2009) · Science · doi:10.1126/science.1167975 · Cited by 960 · see citing works
Walker, D. L., Ressler, K. J., Lu, K.-T., & Davis, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02343.2002 · Cited by 815 · see citing works
Effectiveness of computer-generated (virtual reality) graded exposure in the treatment of acrophobia
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.4.626 · Cited by 694 · see citing works
Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala
Falls, W., Miserendino, M., & Davis, M. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00854.1992 · Cited by 673 · see citing works
The method of minimization for allocation to clinical trials
Scott, N. W., McPherson, G. C., Ramsay, C. R., & Campbell, M. K. (2002) · Controlled Clinical Trials · doi:10.1016/s0197-2456(02)00242-8 · Cited by 651 · cited 1× · see citing works
“Randomization was done by research staff not involved in the trial using minimization procedures (Scott et al., 2002) and stratifying on gender, therapist, and time of day of treatment sessions (before or after 4 pm).”
MethodThe labile nature of consolidation theory
Nader, K., Schafe, G. E., & LeDoux, J. E. (2000) · Nature Reviews Neuroscience · doi:10.1038/35044580 · Cited by 613 · see citing works
Augmentation 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 5× · see citing works
“All rights reserved. http://dx.doi.org/10.1016/j.jpsychires.2012.09.024 disorders (Hofmann et al., 2006; Kushner et al., 2007; Otto et al., 2010; Wilhelm et al., 2008).”
BackgroundMethodInfluentialSelf-citationStability of retrieved memory: Inverse correlation with trace dominance
Eisenberg, M., Kobilo, T., Berman, D. E., & Dudai, Y. (2003) · Science · doi:10.1126/science.1086881 · Cited by 518 · see citing works
A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy
Norberg, M. M., Krystal, J. H., & Tolin, D. F. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.012 · Cited by 510 · see citing works
Effects 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 · see citing works
Reconsolidation 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 · see citing works
Memory reconsolidation mediates the strengthening of memories by additional learning
Lee, J. L. C. (2008) · Nature Neuroscience · doi:10.1038/nn.2205 · Cited by 398 · see citing works
Effects of D-cycloserine on extinction of conditioned freezing.
Ledgerwood, L., Richardson, R., & Cranney, J. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.2.341 · Cited by 388 · see citing works
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 · see citing works
Augmentation of Behavior Therapy With <scp>d</scp> -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 · see citing works
Amygdalar NMDA Receptors are Critical for New Fear Learning in Previously Fear-Conditioned Rats
Lee, H. J., & Kim, J. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08444.1998 · Cited by 310 · see citing works
Efficacy 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 · see citing works
Self-citationde Kleine, R. A., Hendriks, G.-J., Kusters, W. J. C., Broekman, T. G., & van Minnen, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.02.033 · Cited by 220 · see citing works
Comparison of self-report and overt-behavioral procedures for assessing acrophobia
Cohen, D. C. (1977) · Behavior Therapy · doi:10.1016/s0005-7894(77)80116-0 · Cited by 216 · see citing works
Davis, M., & Myers, K. M. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01507-x · Cited by 200 · see citing works
Litz, 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 · see citing works
Self-citationQuartermain, D., Mower, J., Rafferty, M. F., Herting, R. L., & Lanthorn, T. H. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90687-4 · Cited by 190 · see citing works
The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning.
Baker, J. D., & Azorlosa, J. L. (1996) · Behavioral Neuroscience · doi:10.1037//0735-7044.110.3.618 · Cited by 179 · see citing works
The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning.
Baker, J. D., & Azorlosa, J. L. (1996) · Behavioral Neuroscience · doi:10.1037/0735-7044.110.3.618 · Cited by 179 · see citing works
Liu, S., Rovine, M. J., & Molenaar, P. C. M. (2012) · Psychological Methods · doi:10.1037/a0026971 · Cited by 176 · see citing works
A 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 · see citing works
Effects of multiple exposures to d-cycloserine on extinction of conditioned fear in rats
Parnas, A. S., Weber, M. F., & Richardson, R. (2005) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.01.001 · Cited by 146 · see citing works
IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans
D’Souza, D. C., Gil, R. B., Cassello, K., Morrissey, K., Abi‐Saab, D., White, J., Sturwold, R., Bennett, A., Karper, L. P., Zuzarte, E., et al. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00133-x · Cited by 111 · see citing works
Self-directed desensitization for acrophobia
Baker, B. L., Cohen, D. C., & Saunders, J. T. (1973) · Behaviour Research and Therapy · doi:10.1016/0005-7967(73)90071-5 · Cited by 109 · see citing works
Guastella, A. J., Lovibond, P. F., Dadds, M. R., Mitchell, P., & Richardson, R. (2007) · Behaviour Research and Therapy · doi:10.1016/j.brat.2006.07.005 · Cited by 106 · see citing works
Abelson, J. L., & Curtis, G. C. (1989) · Behaviour Research and Therapy · doi:10.1016/0005-7967(89)90091-0 · Cited by 97 · see citing works
The Promise of Extinction Research for the Prevention and Treatment of Anxiety Disorders
Anderson, K. C., & Insel, T. R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.022 · Cited by 87 · see citing works
Grillon, C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.04.017 · Cited by 80 · see citing works
Cognitive 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 67 · see citing works
Self-citationBehavioral and Neuroendocrine Effects of the Partial NMDA Agonist D-cycloserine in Healthy Subjects
van Berckel, B. N. M. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00196-0 · Cited by 53 · see citing works
Właź, P., Baran, H., & Löscher, W. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90132-5 · Cited by 47 · see citing works
Effects of D-Cycloserine Administration on Weekly Nonemotional Memory Tasks in Healthy Participants
Otto, M. W., Basden, S. L., McHugh, R. K., Kantak, K. M., Deckersbach, T., Cather, C., GOFF, D. C., Hofmann, S. G., Berry, A. C., & Smits, J. A. J. (2008) · Psychotherapy and Psychosomatics · doi:10.1159/000172620 · Cited by 36 · see citing works
Self-citationCoelho, C. M., da Silva, C. F., Santos, J. A., Tichon, J., & Wallis, G. M. (2008) · QUT ePrints (Queensland University of Technology) · Cited by 24 · see citing works
Chronic Administration of NMDA Glycine Partial Agonists Induces Tolerance in the Porsolt Swim Test
Lopes, T., Neubauer, P., & Boje, K. M. K. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00302-x · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Singer JD Willett JB Applied longitudinal data analysis: methods for studying change and event occurrence 2003 New York Oxford University Press
Cited by
Sorted by citations
Baldwin, D. S., Anderson, I. M., Nutt, D. J., Allgulander, C., Bandelow, B., den Boer, J. A., Christmas, D. M., Davies, S., Fineberg, N., Lidbetter, N., et al. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881114525674 · Cited by 676 · see citing works
Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review
Botella, C., Fernández-Álvarez, J., Guillén, V., García-Palacios, A., & Baños, R. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0788-4 · Cited by 460 · see citing works
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 · 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
Self-citationVirtual reality in the diagnostic and therapy for mental disorders: A systematic review
Wiebe, A., Kannen, K., Selaskowski, B., Mehren, A., Thöne, A.-K., Pramme, L., Blumenthal, N., Li, M., Asché, L., Jonas, S., et al. (2022) · Clinical Psychology Review · doi:10.1016/j.cpr.2022.102213 · Cited by 223 · see citing works
Exercise augmentation of exposure therapy for PTSD: rationale and pilot efficacy data
Powers, M. B., Medina, J. L., Burns, S., Kauffman, B. Y., Monfils, M., Asmundson, G. J. G., Diamond, A., McIntyre, C., & Smits, J. A. J. (2015) · Cognitive Behaviour Therapy · doi:10.1080/16506073.2015.1012740 · Cited by 194 · see citing works
A meta-analytic examination of attrition in virtual reality exposure therapy for anxiety disorders
Benbow, A. A., & Anderson, P. L. (2019) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2018.06.006 · Cited by 136 · see citing works
Smits, 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 · see citing works
Self-citationSmits, 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. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.06.020 · Cited by 114 · see citing works
“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-citationHofmann, S. G. (2014) · Depression and Anxiety · doi:10.1002/da.22257 · Cited by 108 · see citing works
Self-citationDoes D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis
Rodrigues, H., Figueira, I., Lopes, A., Gonçalves, R., Mendlowicz, M. V., Coutinho, E. S. F., & Ventura, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093519 · Cited by 109 · see citing works
Factors influencing the success of exposure therapy for specific phobia: a systematic review
Böhnlein, J., Altegoer, L., Muck, N. K., Roesmann, K., Redlich, R., Dannlowski, U., & Leehr, E. J. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.009 · Cited by 98 · see citing works
Yohimbine Enhancement of Exposure Therapy for Social Anxiety Disorder: A Randomized Controlled Trial
Smits, J. A. J., Rosenfield, D., Davis, M. L., Julian, K., Handelsman, P. R., Otto, M. W., Tuerk, P., Shiekh, M., Rosenfield, B., Hofmann, S. G., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.008 · Cited by 86 · see citing works
Self-citationEnhancement of psychosocial treatment with D-cycloserine: Models, moderators, and future directions
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. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.007 · Cited by 70 · see citing works
Self-citationd-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders
Hofmann, S. G., Wu, J. Q., & Boettcher, H. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-11 · Cited by 59 · see citing works
Self-citationMcGuire, J. F., Lewin, A. B., & Storch, E. A. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.934677 · Cited by 57 · see citing works
“[33] reveal a more nuanced relationship.”
BackgroundInfluentialBürkner, P.-C., Bittner, N., Holling, H., & Buhlmann, U. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173660 · Cited by 41 · see citing works
Treatment options for the specific phobias
Singh, J., & Singh, J. (2016) · International Journal of Basic and Clinical Pharmacology · doi:10.18203/2319-2003.ijbcp20161496 · Cited by 28 · see citing works
Tolin, D. F. (2017) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2017.08.007 · Cited by 25 · see citing works
A precision medicine approach to pharmacological adjuncts to extinction: A call to broaden research
King, G., Baker, K. D., Bisby, M. A., Chan, D., Cowan, C. S. M., Stylianakis, A. A., Zimmermann, K. S., & Richardson, R. (2019) · Psychopharmacology · doi:10.1007/s00213-018-4999-0 · Cited by 6 · see citing works
- Authors
- 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.
- Affiliations
- Southern Methodist University (US)
- Rush University Medical Center (US)
- Boston University (US)
- Corresponding author
- Tart, Candyce D.
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 47
- Issue
- 2
- Pages
- 168-174
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC3732105
- OpenAlex
- W2049480064
- Cited by
- 75
- References
- 47
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 5 · 2015: 5 · 2014: 15 · 2013: 10
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (NIMH) (R01MH075889)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- D-cycloserine, acrophobia, virtual reality exposure therapy, anxiety disorders, fear extinction, remission
- MeSH terms
- Adolescent, Adult, Aged, Analysis of Variance, Antimetabolites, Avoidance Learning, Cycloserine, Female, Humans, Implosive Therapy, Male, Middle Aged, Neuropsychological Tests, Phobic Disorders, Psychiatric Status Rating Scales, Surveys and Questionnaires, Treatment Outcome, 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
