This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (189)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Cognitive Therapy  • Alert me on articles by topic  Social Bookmarking   What's this?

Use of D-Cycloserine in Phobic Individuals to Facilitate Extinction of Fear

Kerry J. Ressler, MD, PhD; Barbara O. Rothbaum, PhD; Libby Tannenbaum, PhD; Page Anderson, PhD; Ken Graap, MEd; Elana Zimand, PhD; Larry Hodges, PhD; Michael Davis, PhD

Arch Gen Psychiatry. 2004;61:1136-1144.

Background  Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities. However, some disorders, particularly the anxiety-related disorders exemplified by specific phobia, have an emotional learning component to them that can be facilitated with psychotherapy.

Objective  To determine whether D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor that has previously been shown to improve extinction of fear in rodents, will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy.

Design  Randomized, double-blind, placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm.

Setting  Participants were recruited from the general community to a research clinic.

Participants  Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled.

Interventions  After we obtained pretreatment measures of fear, subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator. Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy. Subjects, therapists, and assessors were blind to the treatment condition. Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms.

Main Outcome Measures  Included were measures of acrophobia within the virtual environment, measures of acrophobia in the real world, and general measures of overall improvement. An objective measure of fear, electrodermal skin fluctuation, was also included during the virtual exposure to heights. Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment.

Results  Exposure therapy combined with DCS resulted in significantly larger reductions of acrophobia symptoms on all main outcome measures. Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment (1 week after treatment, P.001; 3 months later, P.05). Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure (P.05). Additionally, subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms (acrophobia avoidance [P.02], acrophobia anxiety [P.01], attitudes toward heights [P.04], clinical global improvement [P.01], and number of self-exposures to real-world heights [P.01]); the improvement was evident early in treatment and was maintained at 3 months.

Conclusion  These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology.

Author Affiliations: Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, Emory University School of Medicine, Atlanta, Ga (Drs Ressler, Rothbaum, and Davis); Yerkes National Primate Center, Atlanta (Drs Ressler and Davis); Virtually Better Inc, Decatur, Ga (Drs Tannenbaum, Anderson, and Zimand and Mr Graap); and Computing Department, University of North Carolina, Charlotte (Dr Hodges).
Financial Disclosure: Drs Davis and Ressler have submitted a patent for the use of D-cycloserine for the specific enhancement of learning during psychotherapy. The terms of these arrangements have been reviewed and approved by Emory University, Atlanta, Ga, and Georgia Institute of Technology, Atlanta, in accordance with their conflict of interest policies.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

D-Cycloserine into the BLA reverses the impairing effects of exposure to stress on the extinction of contextual fear, but not conditioned taste aversion
Akirav et al.
Learn. Mem. 2009;16:682-686.
ABSTRACT | FULL TEXT  

Memory and Brain Systems: 1969-2009
Squire
J. Neurosci. 2009;29:12711-12716.
FULL TEXT  

The Biology of Memory: A Forty-Year Perspective
Kandel
J. Neurosci. 2009;29:12748-12756.
ABSTRACT | FULL TEXT  

Augmentation of Fear Extinction by Infusion of Glycine Transporter Blockers into the Amygdala
Mao et al.
Mol. Pharmacol. 2009;76:369-378.
ABSTRACT | FULL TEXT  

Extinction circuits for fear and addiction overlap in prefrontal cortex
Peters et al.
Learn. Mem. 2009;16:279-288.
ABSTRACT | FULL TEXT  

Posttraumatic Stress Disorder: From Phenomenology to Clinical Practice
Benedek and Ursano
Focus 2009;7:160-175.
ABSTRACT | FULL TEXT  

Guideline Watch (March 2009): Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder
Benedek et al.
Focus 2009;7:204-213.
FULL TEXT  

Variant BDNF Val66Met Polymorphism Affects Extinction of Conditioned Aversive Memory
Yu et al.
J. Neurosci. 2009;29:4056-4064.
ABSTRACT | FULL TEXT  

D-cycloserine potentiates the reconsolidation of cocaine-associated memories
Lee et al.
Learn. Mem. 2009;16:82-85.
ABSTRACT | FULL TEXT  

The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans
Kalisch et al.
Cereb Cortex 2009;19:187-196.
ABSTRACT | FULL TEXT  

Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice
Labrie et al.
Learn. Mem. 2008;16:28-37.
ABSTRACT | FULL TEXT  

Immediate extinction causes a less durable loss of performance than delayed extinction following either fear or appetitive conditioning
Woods and Bouton
Learn. Mem. 2008;15:909-920.
ABSTRACT | FULL TEXT  

Is it time to revisit the role of psychedelic drugs in enhancing human creativity?
Sessa
J Psychopharmacol 2008;22:821-827.
ABSTRACT  

Update on the Assessment, Diagnosis, and Treatment of Individuals with Social Anxiety Disorder
Delong and Pollack
Focus 2008;6:431-437.
ABSTRACT | FULL TEXT  

Novel Treatment Approaches for Refractory Anxiety Disorders
Pollack et al.
Focus 2008;6:486-495.
ABSTRACT | FULL TEXT  

Yohimbine impairs extinction of cocaine-conditioned place preference in an {alpha}2-adrenergic receptor independent process
Davis et al.
Learn. Mem. 2008;15:667-676.
ABSTRACT | FULL TEXT  

Aggression in young children with concurrent callous-unemotional traits: can the neurosciences inform progress and innovation in treatment approaches?
Dadds and Rhodes
Phil Trans R Soc B 2008;363:2567-2576.
ABSTRACT | FULL TEXT  

Impaired Fear Extinction Learning and Cortico-Amygdala Circuit Abnormalities in a Common Genetic Mouse Strain
Hefner et al.
J. Neurosci. 2008;28:8074-8085.
ABSTRACT | FULL TEXT  

Critical Parameters for D-Cycloserine Enhancement of Cognitive-Behaviorial Therapy for Obsessive-Compulsive Disorder
Rothbaum
Am. J. Psychiatry 2008;165:293-296.
FULL TEXT  

Augmentation of Behavior Therapy With D-Cycloserine for Obsessive-Compulsive Disorder
Wilhelm et al.
Am. J. Psychiatry 2008;165:335-341.
ABSTRACT | FULL TEXT  

D-Cycloserine enhances memory consolidation of hippocampus-dependent latent extinction
Gabriele and Packard
Learn. Mem. 2007;14:468-471.
ABSTRACT | FULL TEXT  

Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network.
Kalisch et al.
J. Neurosci. 2006;26:9503-9511.
ABSTRACT | FULL TEXT  

GABAB(1) Receptor Isoforms Differentially Mediate the Acquisition and Extinction of Aversive Taste Memories.
Jacobson et al.
J. Neurosci. 2006;26:8800-8803.
ABSTRACT | FULL TEXT  

Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial.
Walsh et al.
JAMA 2006;295:2605-2612.
ABSTRACT | FULL TEXT  

Combined Psychotherapy and Pharmacotherapy for Mood and Anxiety Disorders in Adults: Review and Analysis
Otto et al.
Focus 2006;4:204.
ABSTRACT | FULL TEXT  

Augmentation of exposure therapy with d-cycloserine for social anxiety disorder.
Hofmann et al.
Arch Gen Psychiatry 2006;63:298-304.
ABSTRACT | FULL TEXT  

Different mechanisms of fear extinction dependent on length of time since fear acquisition.
Myers et al.
Learn. Mem. 2006;13:216-223.
ABSTRACT | FULL TEXT  

Prefrontal Control of the Amygdala
Likhtik et al.
J. Neurosci. 2005;25:7429-7437.
ABSTRACT | FULL TEXT  

Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice
Ponnusamy et al.
Learn. Mem. 2005;12:399-406.
ABSTRACT | FULL TEXT  

Toward a Neurobiology of Psychotherapy: Basic Science and Clinical Applications
Etkin et al.
J. Neuropsychiatry Clin. Neurosi. 2005;17:145-158.
ABSTRACT | FULL TEXT  

Neural Underpinnings of Fear and Its Modulation: Implications for Anxiety Disorders
Miller et al.
J. Neuropsychiatry Clin. Neurosi. 2005;17:1-6.
FULL TEXT