Use of an Antibiotic as an Enhancer for the Treatment of Social Phobia
Condition: Phobic Disorders; Anxiety; Social Phobia
MeSH terms: Phobic Disorders; Phobia, Social
Study type: Interventional
Phase: Phase 2

Summary: 
      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 simple
           choices

      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.
    

Detailed description: 
      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.
    

Intervention name(s): D-Cycloserine; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cognitive; Behavioral; Adolescent; Therapy; Extinction; Social Phobia