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

NCT ID: NCT00128401

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2012-08-31

Brief 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.

Detailed 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.

Conditions

Phobic Disorders; Anxiety; Social Phobia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

D-Cycloserine

An antibiotic, d-cycloserine (DCS) was given to one group and the group is evaluated to see if the drug boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety.

Group Type: ACTIVE_COMPARATOR

D-Cycloserine

Intervention Type: DRUG

Placebo

Another group was given the placebo and tested for effectiveness of cognitive behavior therapy (CBT) for social anxiety.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

D-Cycloserine

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer A Cameron, C.R.N.P.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Mental Health (NIMH)

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Alstrom JE, Nordlund CL, Persson G, Harding 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. doi: 10.1111/j.1600-0447.1984.tb01187.x.

Reference Type: BACKGROUND

PMID: 6148843 (View on PubMed)

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. doi: 10.1037//0022-006x.52.4.642. No abstract available.

Reference Type: BACKGROUND

PMID: 6147366 (View on PubMed)

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. doi: 10.1016/s0006-3223(99)00133-x.

Reference Type: BACKGROUND

PMID: 10704956 (View on PubMed)

Related Links

http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2005-M-0198.html

NIH Clinical Center Detailed Web Page

Other Identifiers

05-M-0198

Identifier Type: -

Identifier Source: secondary_id

050198

Identifier Type: -

Identifier Source: org_study_id