Effect of D-cycloserine Plus Cognitive Behavioral Therapy on People With Social Phobia

Social anxiety disorder (SAD) is among the most common psychiatric conditions and is
associated with significant distress and dysfunction in social situations. Although treatment
with cognitive-behavior therapy (CBT) is known to help remedy SAD, many patients do not
respond to this treatment and most do not reach full recovery. In CBT, patients undergo
repeated and prolonged exposure practices to feared social situations to learn better ways to
deal with anxiety in these settings. Exposure therapy is based on animal models of extinction
of conditioned fears, and recent animal research has identified some of the core pathways and
neurotransmitters involved in fear extinction. D-cycloserine (DCS) is a drug that appears to
facilitate learning and the process of extinction of conditioned fear in both animals and
humans. This study will assess the effectiveness of DCS combined with CBT in treating people
with SAD.

Participants in this double-blind study will be randomly assigned to an active or control
group. All participants will attend 18 study visits at the Center for Anxiety and Related
Disorders over a 9-month period. There will be 12 CBT sessions of 90 minutes each and 6
assessment visits. The CBT sessions will help participants to become more comfortable with
social situations. During 5 of the CBT sessions, participants will receive a pill containing
either DCS or sugar (placebo). Assessment visits will include interviews, self-report
questionnaires, and laboratory tests. These visits will occur at Weeks 1, 7, and 12 during
treatment and at Months 3, 6, and 9 post-treatment.

Inclusion Criteria:

- Meets DSM-IV criteria for generalized social anxiety disorder (GSAD)

- Total score of greater than or equal to 60 on the LSAS

- Physical examination, electrocardiogram, and laboratory findings without clinically
significant abnormalities

Exclusion Criteria:

- Lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders,
or obsessive-compulsive disorder

- Eating disorder within the 6 months prior to study entry

- History of organic brain syndrome, mental retardation, or other cognitive dysfunction

- Substance or alcohol abuse or dependence (other than nicotine) within the 6 months
prior to study entry or inability to refrain from alcohol use during the acute period
of study participation

- Post-traumatic stress disorder within 6 months prior to study entry; entry of patients
with other mood or anxiety disorders will be permitted if the social anxiety disorder
is judged to be the predominant disorder

- Suicidal thoughts

- Taking concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta
blockers) within 2 weeks of study entry

- Significant personality dysfunction

- Serious medical illness or instability for which hospitalization may be likely within
the next year