Social Anxiety Disorder
Conditions
Keywords
Social Phobia
Brief summary
The purpose of this study is to examine the efficacy of 50 mg of d-cycloserine in comparison to placebo (a pill containing no medication) for improving the effectiveness of cognitive-behavioral therapy (CBT) in reducing symptoms associated with social anxiety disorder. In addition, the study will examine whether the effectiveness of d-cycloserine depends on the timing of the pill administration (i.e., 1- hour before the session or immediately after the session) as well as the success of the CBT therapy sessions. The investigators hypothesize that the tailored post-session DCS administration condition will outperform the other conditions (pre-session DCS, placebo, and non-tailored post-session DCS). This will be evidenced by short- and long-term improvements in social anxiety severity.
Interventions
BEHAVIORALCognitive Behavioral Therapy
This will be a 5-session version of a group CBT protocol with 4-6 patients and 2 therapists per group emphasizing repeated exposure practices. Session 1 involves an introduction and orientation to the CBT model. Sessions 2-5 emphasize repeated exposure tasks, which consist of role-play activities to confront fearful situations in a group setting while disputing cognitive distortions (coupled with the fading of safety behaviors). At the conclusion of each exposure session, patients will be encouraged to continue to apply home-practice strategies (such as giving speeches in front of a mirror). Continued practice of the interventions will be considered part of treatment, and patients will be asked to refrain from alternative treatment for four weeks following completion of the last treatment session.
DRUGD-Cycloserine
D-cycloserine is a medication thought to be associated with fear extinction.
DRUGPlacebo
Sugar pill
Sponsors
Jasper A. Smits
Rush University Medical Center
Boston University
Southern Methodist University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female outpatients \> 18 years of age with a primary psychiatric diagnosis (designated by the patient as the most important source of current distress) of social anxiety disorder as defined by DSM-5 criteria. * A total score \> 60 on the LSAS. * Physical examination and laboratory findings without clinically significant abnormalities. * Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.
Exclusion criteria
* A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation. * PTSD within the past 6 months. Entry of patients with other mood or anxiety disorders will be permitted if the SAD is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score \> 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention. * Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment. * Significant personality dysfunction likely to interfere with study participation. * Serious medical illness or instability for which hospitalization may be likely within the next year. * Patients with a current or past history of seizures. * Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months). * Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the SAD is excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and providing management skills. General supportive therapy initiated \> 3 months prior is acceptable. * Prior non-response to adequately-delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment). * Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment. Current use of isoniazid or ethionamide compounds * Insufficient command of the English language
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Social Anxiety Symptom Severity | Assessments took place at multiple time points from baseline to 3-month follow-up. The three-month is reported | The main outcome was a composite Z-score from the Liebowitz Social Anxiety Scale (LSAS) and the Social Phobic Disorders Severity and Change Form (SPD-SC Form). "The Composite Z-score of the LSAS and SPD-SC Form indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population. Negative numbers indicate values lower symptom severity and positive numbers indicate higher symptom severity. The LSAS is a 24-item scale that measures fear and avoidance in social and performance situations within the last week, using 0 (no fear/never avoids) to 3 (severe fear/usually avoids) scale. LSAS scores range from 0-144 with higher scores indicated worse outcomes. The SPD-S is the Clinical Global Impression Scale27 adapted for SAD, which instructs evaluators to use a 7-point scale (1=normal, not at all ill; 7=among the most extremely ill patients) to index the severity of social anxiety. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMark Pollack, M.D.
Rush University Medical Center
PRINCIPAL_INVESTIGATORStefan Hofmann, Ph.D.
Boston University
PRINCIPAL_INVESTIGATORJasper A Smits, Ph.D.
University of Texas at Austin
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tailored Post-Session DCS Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one dcs/placebo after the session). DCS will be administered if the session is deemed a success.
D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction.
Placebo: Sugar pill | 40 |
| Pre-Session DCS Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one dcs before and one placebo after the session).
D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction.
Placebo: Sugar pill | 38 |
| Placebo Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one placebo after the session).
Placebo: Sugar pill | 38 |
| Non-Tailored Post-Session DCS Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one dcs after the session).
D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction.
Placebo: Sugar pill | 36 |
| Total | 152 |
Baseline characteristics
| Characteristic | Tailored Post-Session DCS | Pre-Session DCS | Placebo | Non-Tailored Post-Session DCS | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 38 Participants | 38 Participants | 36 Participants | 152 Participants |
| Age, Continuous | 30.78 Years STANDARD_DEVIATION 9.88 | 29.73 Years STANDARD_DEVIATION 10.42 | 28.76 Years STANDARD_DEVIATION 11.81 | 27.54 Years STANDARD_DEVIATION 8.29 | 29.20 Years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 10 Participants | 9 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 32 Participants | 26 Participants | 25 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 7 Participants | 8 Participants | 13 Participants | 34 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 5 Participants | 4 Participants | 3 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 25 Participants | 23 Participants | 24 Participants | 18 Participants | 90 Participants |
| Region of Enrollment United States | 40 participants | 38 participants | 38 participants | 36 participants | 152 participants |
| Sex: Female, Male Female | 24 Participants | 22 Participants | 18 Participants | 21 Participants | 85 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 20 Participants | 15 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 38 | 0 / 38 | 0 / 36 |
| other Total, other adverse events | 0 / 40 | 0 / 38 | 0 / 38 | 0 / 36 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 | 1 / 38 | 0 / 36 |
Outcome results
Primary
Social Anxiety Symptom Severity
The main outcome was a composite Z-score from the Liebowitz Social Anxiety Scale (LSAS) and the Social Phobic Disorders Severity and Change Form (SPD-SC Form). The Composite Z-score of the LSAS and SPD-SC Form indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population. Negative numbers indicate values lower symptom severity and positive numbers indicate higher symptom severity. The LSAS is a 24-item scale that measures fear and avoidance in social and performance situations within the last week, using 0 (no fear/never avoids) to 3 (severe fear/usually avoids) scale. LSAS scores range from 0-144 with higher scores indicated worse outcomes. The SPD-S is the Clinical Global Impression Scale27 adapted for SAD, which instructs evaluators to use a 7-point scale (1=normal, not at all ill; 7=among the most extremely ill patients) to index the severity of social anxiety.
Time frame: Assessments took place at multiple time points from baseline to 3-month follow-up. The three-month is reported
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tailored Post-Session DCS | Social Anxiety Symptom Severity | -.46 score on a scale | Standard Error 0.13 |
| Pre-Session DCS | Social Anxiety Symptom Severity | -.90 score on a scale | Standard Error 0.13 |
| Placebo | Social Anxiety Symptom Severity | -.39 score on a scale | Standard Error 0.14 |
| Non-Tailored Post-Session DCS | Social Anxiety Symptom Severity | -.88 score on a scale | Standard Error 0.14 |
Comparison: At 3 month follow-upp-value: <0.00195% CI: [-0.81, -0.21]Mixed Models Analysis
Comparison: 3 month follow-upp-value: 0.63595% CI: [-0.37, 0.23]Mixed Models Analysis
p-value: 0.00295% CI: [-0.8, -0.18]Mixed Models Analysis
Comparison: 3 month follow-upp-value: 0.00495% CI: [-0.73, -0.14]Mixed Models Analysis
Comparison: 3 month follow-upp-value: 0.00895% CI: [-0.72, -0.11]Mixed Models Analysis