Cognitive Enhancers as Adjuncts to Psychotherapy: Use of D-Cycloserine in Phobic Individuals to Facilitate Extinctionof Fear | Anxiety Disorders | JAMA Psychiatry | JAMA Network
[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Article
November 2004

Cognitive Enhancers as Adjuncts to Psychotherapy: Use of D-Cycloserine in Phobic Individuals to Facilitate Extinctionof Fear

Author Affiliations

Author Affiliations: Department of Psychiatryand Behavioral Sciences, Center for Behavioral Neuroscience, Emory UniversitySchool of Medicine, Atlanta, Ga (Drs Ressler, Rothbaum, and Davis); YerkesNational Primate Center, Atlanta (Drs Ressler and Davis); Virtually BetterInc, Decatur, Ga (Drs Tannenbaum, Anderson, and Zimand and Mr Graap); andComputing Department, University of North Carolina, Charlotte (Dr Hodges). Financial Disclosure: Drs Davis and Resslerhave submitted a patent for the use of D-cycloserine for the specific enhancementof learning during psychotherapy. The terms of these arrangements have beenreviewed and approved by Emory University, Atlanta, Ga, and Georgia Instituteof Technology, Atlanta, in accordance with their conflict of interest policies.

Arch Gen Psychiatry. 2004;61(11):1136-1144. doi:10.1001/archpsyc.61.11.1136

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.