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

Phase 3

Completed

Conditions: Social Anxiety Disorder

Interventions: Drug: D-cycloserine
Behavioral: Cognitive behavioral therapy (CBT)
Drug: Placebo

Registration Number: NCT00515879

Lead Sponsor: Boston University Charles River Campus

Brief Summary: This study will assess the effectiveness of D-cycloserine combined with cognitive-behavior therapy in treating people with social anxiety disorder.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 169

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CBT plus d-cycloserine	Cognitive behavioral therapy (CBT)	Participants will receive cognitive behavioral therapy plus D-cycloserine
CBT plus placebo	Cognitive behavioral therapy (CBT)	Participants will receive cognitive behavioral therapy plus pill placebo
CBT plus placebo	Placebo	Participants will receive cognitive behavioral therapy plus pill placebo
CBT plus d-cycloserine	D-cycloserine	Participants will receive cognitive behavioral therapy plus D-cycloserine

Primary Outcome Measures

Name	Time	Method
Liebowitz Social Anxiety Scale (LSAS)	Measured at Months 3	The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations; it is widely used in treatment studies of SAD. Total scores range from 0 (no anxiety) to 144 (maximum).
Social Phobic Disorders Severity and Change Form	Measured at Months 3 (immediately after treatment)	Social Phobic Disorders Severity and Change Form (SPD-SC Form; Liebowitz et al., 1992) is an expansion and adaptation of the Clinical Global Impression Scale (CGI) by Guy (1976) to SAD. Similar to the original CGI scale, the SPD-SC Form is rated by an independent evaluator on a 7-point scale to indicate severity (1=normal/not ill; 2 = minimally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most severely ill) and improvement (1=very much improved; 2=much improved; . 3=minimally improved' 4 = no change; 5=nimimal deterioration; 6=severe deterioration; 7=very severe deterioration). The primary outcome measure is units of a scale ranging from 1 (very much improved) to 7 (very severe deterioration).

Secondary Outcome Measures

Name	Time	Method
Range of Impaired Functioning Tool	Measured at Months 3, 6, and 9 post-treatment	The Range of Impaired Functioning Tool (LIFE-RIFT, Leon et al., 2000) is a clinician rated scale assessing functioning in four domains: work, interpersonal relationships, recreation, and global satisfaction. Each domain is scored 0-5 (0=not applicable, 1=no impairment, 2=slight impairment, 3=mild impairment, 4=moderate impairment, 5=severe impairment). The total score is the sum of each domain's score, with a maximum score of 20 (severe impairment) and a minimum score of 4 (no impairment).
Social Phobia and Anxiety Inventory	Measured at Months 3, 6, and 9 post-treatment	The Social Phobia and Anxiety Inventory (SPAI; Turner, Beidel, Dancu, and Stanley, 1989) is a 45-item self-report measure on the frequency (0 = Never, 1 = Very Infrequent, 2 = Infrequent, 3 = Sometimes, 4 = Frequent, 5 = Very Frequent, 6 = Always) of one's experiences. The inventory includes 32 items assessing somatic, cognitive, and behavioral symptoms of social anxiety and 13 items assessing agoraphobia. The final score is calculated by subtracting the agoraphobia subscale total (max = 78; min = 0) from the social phobia subscale total (max = 192; min = 0). Thus, the final total scores range from 0-114, where higher final scores indicate higher social anxiety.
Quality of Life Enjoyment and Satisfaction Questionnaire	Measured at Months 3, 6, and 9 post-treatment	The Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott et al., 1993) is a 16-item self-report measure that rates aspects of quality of life, including physical health, mood, activities of daily living, and overall life satisfaction. Responses are scored on a 5 point scale. The maximum score is 70 (high satisfaction) and the minimum is 14 (low satisfaction); scores are generally expressed as a percentage of maximum total score (0-100).
Liebowitz Self-Rated Disability Scale	Measured at Months 3, 6, and 9 post-treatment	Liebowitz Self-Rated Disability Scale (Schneier et al., 1994) is an 11-item scale assessing impairment specific to social anxiety. Current (past 2 weeks) and most severe lifetime impairment due to social anxiety disorder are rated on a 0-3 scale of degree of limitation (0=problem does not limit me at all; 3=problem limits me severely). The maximum score is 44 (severe impairment) and the minimum is 0 (no impairment).