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Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive Enhancers as Adjuncts to Psychotherapy: Use of D-Cycloserine in Phobic Individuals to Facilitate Extinctionof Fear. Arch Gen Psychiatry. 2004;61(11):1136–1144. doi:10.1001/archpsyc.61.11.1136
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
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.
Randomized, double-blind, placebo-controlled trial examining DCS vs
placebo treatment in combination with a precisely controlled exposure paradigm.
Participants were recruited from the general community to a research
Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical
Interview for DSM-IV were enrolled.
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
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.
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.
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