Augmentation of Behavior Therapy With d -Cycloserine for Obsessive-Compulsive Disorder
Abstract
OBJECTIVE: This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). METHOD: A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. RESULTS: Relative to the placebo group, the D-cycloserine group's OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine group's depressive symptoms were significantly more improved at posttreatment. CONCLUSIONS: These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist.
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Research demonstrated that relative to placebo, patients taking d-cycloserine before exposure therapy experienced faster rate of symptom improvement in first few weeks of ERP.
“research demonstrated that, relative to those given a placebo pill, patients taking d-cycloserine before engaging in exposure therapy experienced a faster rate of symptom improvement in the first few weeks of receiving ERP.[57]”
From Exposure and response prevention for obsessive-compulsive disorder: A review and new directions (2019) · cites this paper as [57]
The weak or null effects observed in previous studies of pre-session DCS may be accounted for by large individual variability in fear extinction observed in therapy sessions.
“The findings of the present study suggest that the weak or null effects observed in these previous studies may be accounted for by large individual variability in fear extinction observed in therapy sessions.”
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 [14]
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Self-citationStructural Determinants of d-Cycloserine Efficacy at the NR1/NR2C NMDA Receptors
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Need for speed: Evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine
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Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction
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Fear Processing, Psychophysiology, and PTSD
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“While traditional anxiolytics such as the benzodiazepines or selective serotonin reuptake inhibitors reduce symptom expression, DCS facilitates the effectiveness of EBT (1-5).”
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Critical brain circuits at the intersection between stress and learning
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Self-citationd-Cycloserine Augmentation of Cognitive Behavioral Therapy for Anxiety Disorders: an Update
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Augmentation of exposure therapy with post-session administration of D-cycloserine
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Glutamatergic modulatory therapy for Tourette syndrome
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Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans
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D-Cycloserine Effects on Extinction of Conditioned Responses to Drug-Related Cues
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Behavioral changes in G72/G30 transgenic mice
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Investigating the Role of Glutamate in Obsessive-Compulsive Disorder: Current Perspectives
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- Authors
- Wilhelm, S., Buhlmann, U., Tolin, D. F., Meunier, S. A., Pearlson, G. D., Reese, H. E., Cannistraro, P., Jenike, M. A., & Rauch, S. L.
- Affiliations
- Harvard University (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2008-03
- Volume
- 165
- Issue
- 3
- Pages
- 335-341
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2038335379
- Semantic Scholar
- d1309dc52689e30eae911778d6e9c8b6cc61a87f
- Cited by
- 358
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 16 · 2017: 24 · 2016: 13 · 2015: 24 · 2014: 36 · 2013: 33 · 2012: 41
- FWCI
- 48.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- D-cycloserine, obsessive-compulsive disorder, behavior therapy, augmentation therapy, NMDA receptor partial agonist, glutamatergic pathways, long-term potentiation, depressive symptoms
- MeSH terms
- Adult, Animals, Behavior Therapy, Combined Modality Therapy, Cycloserine, Double-Blind Method, Female, Follow-Up Studies, Humans, Implosive Therapy, Obsessive-Compulsive Disorder, Placebos, Psychiatric Status Rating Scales, Severity of Illness Index, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders, Rats, Secondary Prevention
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