Use of an Antibiotic as an Enhancer for the Treatment of Social Phobia

Anxiety Clinical Trial

Official title:

Effect of D-Cycloserine on Treatment of Social Phobia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00128401
• Other study ID #: 050198
• Secondary ID: 05-M-0198
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2005
• Last updated: April 17, 2014
• Start date: August 2005
• Est. completion date: August 2012

Study information

• Verified date: April 2014
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: August 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 55 Years

Eligibility

• INCLUSION CRITERIA:

1. Subjects between 8 yrs of age (preadolescents) and under 55 yrs of age.

2. Subjects medically healthy.

3. Able to give informed consent.

4. Not on psychotropic meds for a minimum of 6 weeks for fluoxetine; a minimum of 1 week for PRN benzodiazepines and beta blockers, and a minimum of 3 weeks for all other psychotropic meds.

5. Subjects diagnosed with DSM IV symptoms of social phobia, generalized or specific type.

EXCLUSION CRITERIA:

1. Current major depressive disorder.

2. Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental retardation, substance or alcohol dependence (other than nicotine); active suicidal ideation.

3. Current or lifetime history of a neurological disorder (other than tic disorders, febrile seizures of infancy), seizure disorder.

4. Any unstable medical condition.

5. Use of any psychoactive substance in the past 30 days.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety
• Phobic Disorders
• Social Phobia

Intervention

Drug:
• D-Cycloserine

• Placebo

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Alström JE, Nordlund CL, Persson G, Hårding M, Ljungqvist C. Effects of four treatment methods on social phobic patients not suitable for insight-oriented psychotherapy. Acta Psychiatr Scand. 1984 Aug;70(2):97-110. — View Citation

Butler G, Cullington A, Munby M, Amies P, Gelder M. Exposure and anxiety management in the treatment of social phobia. J Consult Clin Psychol. 1984 Aug;52(4):642-50. — View Citation

D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper LP, Zuzarte E, Charney DS, Krystal JH. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biol Psychiatry. 2000 Mar 1;47(5):450-62. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Global Improvement (CGI-S) Scale	Symptom severity and improvement was assessed using the Clinical Global Impressions scale (CGI). It is a 2-item clinician-administered instrument that measures the patients' illness severity and global improvement. The minimum value for the CGI is 1=Normal, not at all ill and the maximum value is 7=Among the most extremely ill patients.	12 weeks post baseline	No
Secondary	Liebowitz Social Anxiety Scale (LSAS)	Social anxiety symptoms were assessed using the Liebowitz Social Anxiety Scale (LSAS). It is a 24-item self-report instrument that measures overall social anxiety fear and avoidance symptoms. This is the baseline assessment. The 24 items are each rated twice, from a "0" to "3" scale, with "0" indicated no level of symptom and "3" indicating a high level of the system. One rating is for anxiety, and the other is for avoidance. Thus, the lowest possible score is 0, and the highest possible score is 144. The total score represents the simple sum of all 48 ratings.	12 weeks post baseline	No