Social Anxiety Disorder
Conditions
Keywords
Generalized subtype
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.
Interventions
DRUGD-cycloserine
50 mg
BEHAVIORALCognitive behavioral therapy (CBT)
CBT sessions aim to help participants become more comfortable with social situations.
DRUGPlacebo
Same dosage as active pill
Sponsors
National Institute of Mental Health (NIMH)
Boston University Charles River Campus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
Countries
United States
Participant flow
Recruitment details
Prospective participants were recruited between September 2007 and June 2011 through referrals to the three study sites (Boston University \[BU\], Massachusetts General Hospital \[MGH\], and Southern Methodist University \[SMU\]), from other area clinical facilities and programs, and from advertisements.
Pre-assignment details
Study participants underwent a two-step screening evaluation, consisting of 1) telephone screening, and 2) psychiatric assessment and medical history taking with physical examination.
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine-augmented CBT Participants will receive D-cycloserine augmented cognitive behavioral therapy | 87 |
| Placebo-augmented CBT Participants will receive placebo augmented cognitive behavioral therapy | 82 |
| Total | 169 |
Baseline characteristics
| Characteristic | Placebo-augmented CBT | D-cycloserine-augmented CBT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants | 87 Participants | 169 Participants |
| Age, Continuous | 30.5 years STANDARD_DEVIATION 8.9 | 34.6 years STANDARD_DEVIATION 7.89 | 32.55 years STANDARD_DEVIATION 8.41 |
| Region of Enrollment United States | 82 participants | 87 participants | 169 participants |
| Sex: Female, Male Female | 30 Participants | 44 Participants | 74 Participants |
| Sex: Female, Male Male | 52 Participants | 43 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 87 | 0 / 82 |
| serious Total, serious adverse events | 0 / 87 | 0 / 82 |
Outcome results
Primary
Liebowitz Social Anxiety Scale (LSAS)
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).
Time frame: Measured at Months 3
| Arm | Measure | Value (MEAN) |
|---|---|---|
| D-cycloserine-augmented CBT | Liebowitz Social Anxiety Scale (LSAS) | 39.19 LSAS scores |
| Placebo-augmented CBT | Liebowitz Social Anxiety Scale (LSAS) | 42.44 LSAS scores |
Primary
Social Phobic Disorders Severity and Change Form
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).
Time frame: Measured at Months 3 (immediately after treatment)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| D-cycloserine-augmented CBT | Social Phobic Disorders Severity and Change Form | 2.68 Units on a scale |
| Placebo-augmented CBT | Social Phobic Disorders Severity and Change Form | 2.95 Units on a scale |
Secondary
Liebowitz Self-Rated Disability Scale
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).
Time frame: Measured at Months 3, 6, and 9 post-treatment
Population: The number of analyzed participants differs from the overall number analyzed due to participant dropout between treatment and subsequent follow up time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine-augmented CBT | Liebowitz Self-Rated Disability Scale | 3 Months | 15.6117 score on a scale | Standard Deviation 7.25681 |
| D-cycloserine-augmented CBT | Liebowitz Self-Rated Disability Scale | 6 Months | 15.5283 score on a scale | Standard Deviation 7.03686 |
| D-cycloserine-augmented CBT | Liebowitz Self-Rated Disability Scale | 9 Months | 15.3269 score on a scale | Standard Deviation 7.72461 |
| Placebo-augmented CBT | Liebowitz Self-Rated Disability Scale | 3 Months | 14.0303 score on a scale | Standard Deviation 7.79688 |
| Placebo-augmented CBT | Liebowitz Self-Rated Disability Scale | 6 Months | 14.4977 score on a scale | Standard Deviation 7.9847 |
| Placebo-augmented CBT | Liebowitz Self-Rated Disability Scale | 9 Months | 14.3130 score on a scale | Standard Deviation 7.6263 |
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire
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).
Time frame: Measured at Months 3, 6, and 9 post-treatment
Population: The number of analyzed participants differs from the overall number analyzed due to participant dropout between treatment and subsequent follow up time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 3 Months | 67.77 percentage of maximum | Standard Deviation 14.075 |
| D-cycloserine-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 6 Months | 66.32 percentage of maximum | Standard Deviation 16.066 |
| D-cycloserine-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 9 Months | 67.08 percentage of maximum | Standard Deviation 16.063 |
| Placebo-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 3 Months | 67.44 percentage of maximum | Standard Deviation 14 |
| Placebo-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 6 Months | 67.44 percentage of maximum | Standard Deviation 14.872 |
| Placebo-augmented CBT | Quality of Life Enjoyment and Satisfaction Questionnaire | 9 Months | 69.58 percentage of maximum | Standard Deviation 11.761 |
Secondary
Range of Impaired Functioning Tool
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).
Time frame: Measured at Months 3, 6, and 9 post-treatment
Population: The number of analyzed participants differs from the overall number analyzed due to participant dropout between treatment and subsequent follow up time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine-augmented CBT | Range of Impaired Functioning Tool | 3 Months | 8.5256 score on a scale | Standard Deviation 2.78 |
| D-cycloserine-augmented CBT | Range of Impaired Functioning Tool | 6 Months | 8.6143 score on a scale | Standard Deviation 2.6773 |
| D-cycloserine-augmented CBT | Range of Impaired Functioning Tool | 9 Months | 8.6232 score on a scale | Standard Deviation 2.80284 |
| Placebo-augmented CBT | Range of Impaired Functioning Tool | 3 Months | 8.6667 score on a scale | Standard Deviation 2.80841 |
| Placebo-augmented CBT | Range of Impaired Functioning Tool | 6 Months | 8.5430 score on a scale | Standard Deviation 2.82987 |
| Placebo-augmented CBT | Range of Impaired Functioning Tool | 9 Months | 7.7458 score on a scale | Standard Deviation 2.43957 |
Secondary
Social Phobia and Anxiety Inventory
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.
Time frame: Measured at Months 3, 6, and 9 post-treatment
Population: The number of analyzed participants differs from the overall number analyzed due to participant dropout between treatment and subsequent follow up time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine-augmented CBT | Social Phobia and Anxiety Inventory | 3 Months | 71.08 score on a scale | Standard Deviation 28.585 |
| D-cycloserine-augmented CBT | Social Phobia and Anxiety Inventory | 6 Months | 69.64 score on a scale | Standard Deviation 32.188 |
| D-cycloserine-augmented CBT | Social Phobia and Anxiety Inventory | 9 Months | 67.67 score on a scale | Standard Deviation 31.847 |
| Placebo-augmented CBT | Social Phobia and Anxiety Inventory | 3 Months | 73.74 score on a scale | Standard Deviation 30.311 |
| Placebo-augmented CBT | Social Phobia and Anxiety Inventory | 6 Months | 71.97 score on a scale | Standard Deviation 30.566 |
| Placebo-augmented CBT | Social Phobia and Anxiety Inventory | 9 Months | 67.74 score on a scale | Standard Deviation 33.289 |