This study examines whether an antibiotic, d-cycloserine (DCS), boosts the effectiveness of
cognitive behavior therapy (CBT) for social anxiety. CBT has been shown to be effective for
the treatment of social anxiety in children and adults, but even after treatment,
approximately 40% may remain diagnosable. The antibiotic DCS has been shown to enhance the
type of learning that is promoted by exposure therapy, a main component of CBT. This study
will test whether DCS can improve the effectiveness of CBT for social anxiety.
All participants will receive 12 weekly CBT sessions. In addition to receiving the CBT,
participants will be randomly assigned (similar to a coin toss) to receive either DCS or a
placebo (sugar pill). The pill will be taken 1-2 hours prior to each of the 12 CBT
sessions. The pill is taken only on the 12 therapy days.
Prior to receiving treatment, participants will be asked to:
- participate in interviews to assess diagnosis and how they are doing including mood,
degree of nervousness and behavior
- have a physical examination, a urine test, and an electrocardiogram (EKG)
- undergo tests involving problem-solving and memory
- prepare and present a speech to a "virtual audience" using virtual reality goggles
- undergo functional magnetic resonance imaging (fMRI) while performing tasks that
involve looking at pictures, remembering things, testing reaction times, and making
Those who have not improved by the end of the study will be offered standard antianxiety
medication treatment for 1 to 3 months. If a participant does not wish to take medication,
study clinicians will help him/her locate psychological care in the community. Participants
will be asked to complete a follow-up assessment 3 months after their last CBT session.
Social phobia afflicts between 3%-15% of the US population. As such, it is a particularly
common debilitating psychiatric disorder. Like many anxiety disorders, social phobia
typically arises during adolescence. Treatment has consisted of medication or cognitive
behavioral therapy (CBT). Selective Serotonin Reuptake Inhibitors (SSRIs) represent the
first-line pharmacological treatment both in adults as well as adolescents (APA Treatment
Guidelines 2004). Similarly, CBT significantly improves outcome in both age groups. This
treatment consists of psychoeducation, exposure therapy, and cognitive restructuring. While
both treatments produce clinically meaningful benefits, most patients exhibiting positive
responses to these treatments continue to exhibit marked residual symptoms, if not
full-blown anxiety disorders. Thus, there is great need for treatment advances.
Intense fear of social scrutiny represents a core component of social phobia, and extinction
of this fear represents the goal of exposure therapy during CBT (Cohn and Hope). Finding
treatments that facilitate extinction is of paramount importance. In animals, extinction
involves an active learning process that is blocked by glutamatergic NMDA antagonists and
facilitated by NMDA agonists. Specifically, administration of D-cycloserine (DCS), a
partial agonist at the glycine modulatory site on the NMDA receptor, produces a
dose-dependent facilitation of extinction in the rat. As such, DCS might facilitate
extinction during exposure-based CBT. Indeed, Ressler (Ressler et al 2004) recently
reported preliminary data from a clinical trial supporting this hypothesis.
We will examine the degree to which DCS treatment can augment the clinical response in
social phobia to CBT-exposure-based therapy. Specifically, we will study two groups of
individuals with social phobia, both of whom will receive CBT. One group will receive
placebo; a second group will receive 50 mg of D-cycloserine 1-2 hours before each exposure
therapy session. We hypothesize that compared to placebo, DCS will produce greater
reductions in social anxiety symptoms following CBT treatment. Finally, given that chronic
social anxiety disorder virtually always begins during childhood, it is particularly vital
to develop early interventions for the disorder. Accordingly, our trial will examine both
adolescents and adults with the disorder.
- INCLUSION CRITERIA:
1. Subjects between 8 yrs of age (preadolescents) and under 55 yrs of age.
2. Subjects medically healthy.
3. Able to give informed consent.
4. Not on psychotropic meds for a minimum of 6 weeks for fluoxetine; a minimum of 1
week for PRN benzodiazepines and beta blockers, and a minimum of 3 weeks for all
other psychotropic meds.
5. Subjects diagnosed with DSM IV symptoms of social phobia, generalized or
1. Current major depressive disorder.
2. Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental
retardation, substance or alcohol dependence (other than nicotine); active suicidal
3. Current or lifetime history of a neurological disorder (other than tic disorders,
febrile seizures of infancy), seizure disorder.
4. Any unstable medical condition.
5. Use of any psychoactive substance in the past 30 days.