Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder

Condition(s) targeted: Social Phobia

Intervention: Clonazepam (Drug); Venlafaxine (Drug); Sertraline (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Mark H. Pollack, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
Murray B. Stein, MD, MPH, Principal Investigator, Affiliation: University of California San Deigo
Michael Van Ameringen, MD, FRCPC, Principal Investigator, Affiliation: Anxiety Disorders Clinic McMaster Univeristy Medical Centre

Overall contact:
Nannette N. Herlands, BA, Phone: 617-726-1570, Email: nherlands@partners.org

This study will compare the effectiveness of either adding clonazepam or placebo to standard treatment or switching to venlafaxine in treating generalized social anxiety disorder in individuals who have not responded to treatment with sertraline.

Official title: Improving Outcomes in Pharmacotherapy of Social Phobia

Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Remission rates less than 30 on the Liebowitz Social Anxiety Scale (LSAS)

Post-treatment social phobia severity as defined by endpoint LSAS scores

Secondary outcome: Treatment response

Detailed description: Generalized social anxiety disorder (GSAD) is one of the most common psychiatric disorders, and often causes significant distress and dysfunction in affected individuals. Although currently available treatments for GSAD are effective, most individuals have residual symptoms after initial psychosocial or psychopharmacologic intervention. Further treatment is necessary for such individuals, but sufficient research has not been done to guide clinicians on what the safest and most effective next step may be. This study will compare the effectiveness of either combining clonazepam or placebo with sertraline or completely switching to venlafaxine in treating GSAD in individuals who have not responded to treatment with sertraline. This study will also examine predictors of treatment response, including factors such as age at disease onset, duration of illness, comorbidities, and genes that influence serotonin and catecholamine metabolism.

Participants in this double-blind study will first partake in an initial 10-week phase in which they will be treated with sertraline. Participants who do not respond to sertraline treatment will proceed to phase two of the study, in which they will be randomly assigned to one of three treatment groups. One group will receive both sertraline and clonazepam, another group will receive both sertraline and placebo, and the third group will receive only venlafaxine. All treatments will continue for 12 weeks. Sertraline and venlafaxine are both FDA-approved for the treatment of GSAD. Clonazepam is widely used for the treatment of anxiety, but is not FDA-approved for the treatment of GSAD. All participants will attend weekly study visits at Weeks 1, 2, 4, 6, 8, and 10. Participants who continue into phase two will attend weekly study visits at Weeks 11-14, 16, 18, 20, and 22. Symptom remission rates and post-treatment social phobia severity will be assessed at Week 20.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Primary psychiatric diagnosis of GSAD as defined by DSM-IV criteria and a score above

60 on the LSAS

- Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

- Clinically significant abnormalities found upon physical examination,

electrocardiogram, and laboratory tests

- History of more than two unsuccessful, adequate treatment trials, indicated by a lack

of response to over 10 weeks of any of the following: SSRIs (e. g., 40 mg of paroxetine or its equivalent per day); benzodiazepine (e. g. at least 2. 5 mg of clonazepam per day) plus antidepressant (adequate dose as above); monoamine oxidase inhibitors (e. g., 60 mg of phenelzine or its equivalent per day); or a single failed trial of over 10 weeks of venlafaxine ( at least 150 mg per day)

- Pregnant or breastfeeding

- Simultaneous use of other psychotropic medications; participants must discontinue

regular benzodiazepine or antidepressant therapy at least two weeks (5 weeks for fluoxetine) prior to study entry; beta-blockers must be discontinued unless they are indicated medically (e. g., for hypertension)

- DSM-IV diagnosis of any of the following: lifetime history of schizophrenia or any

other psychosis, mental retardation, organic medical disorder, bipolar disorder, or obsessive compulsive disorder; eating disorder in the past 6 months; alcohol or substance abuse in the past 3 months or dependence within the past 6 months (entry of participants with major depression, dysthymia, panic disorder, generalized anxiety disorder, or post-traumatic stress disorder will be permitted if the social anxiety disorder is judged to be the predominant disorder)

- Significant suicidal ideation as indicated by a score greater than 3 on the

Montgomery-Asberg Depression Rating Scale or suicidal behaviors within 6 months prior to study entry

- Significant personality dysfunction that could interfere with study participation

- Serious medical illness or instability for which hospitalization may be likely during

the study

- Seizure disorders, with the exception of a childhood history of isolated,

non-recurrent febrile seizures

- Any concurrent psychotherapy initiated within 3 months of study entry, or ongoing

psychotherapy of any duration directed specifically toward treatment of GSAD (prohibited psychotherapy includes cognitive behavioral therapy or psychodynamic therapy that focuses on exploring specific, dynamic causes of the phobic symptomatology and that provides management skills; general supportive therapy for more than 3 months is acceptable)

Nannette N. Herlands, BA, Phone: 617-726-1570, Email: nherlands@partners.org

University of California San Diego, La Jolla, California 92093, United States; Recruiting
Murray B. Stein, MD, MPH, Phone: 858-534-6400, Email: mstein@UCSD.Edu
Murray B. Stein, MD, MPH, Principal Investigator
Denise A. Chavira, PhD, Sub-Investigator
Laura Campbell-Sills, PhD, Sub-Investigator
Scott C. Matthews, MD, Sub-Investigator
Ann Fleming, RN, Sub-Investigator

Center for Anxiety and Traumatic Stress Disorders, Boston, Massachusetts 02116, United States; Recruiting
Nannette N. Herlands, BA, Phone: 617-736-1570, Email: nherlands@partners.org
Mark H. Pollack, MD, Principal Investigator
Naomi M. Simon, MD, MSC, Sub-Investigator
John J. Worthington, MD, Sub-Investigator
Elizabeth A. Hoge, MD, Sub-Investigator
David A. Schoenfeld, PhD, Sub-Investigator
David J. Dorer, PhD, Sub-Investigator

McMaster University Medical Centre Anxiety Disorders Clinic, Hamilton, Ontario L8N 3Z5, Canada; Recruiting
Michael Van Ameringen, MD, FRCPC, Phone: 905-521-2100, Ext: 76181, Email: vanamer@mcmaster.ca
Michael Van Ameringen, MD, FRCPC, Principal Investigator
Catherine Mancini, MD, FRCPC, Sub-Investigator
Jonathan Oakman, PhD, Sub-Investigator
Beth Patterson, BScN, RN, Sub-Investigator

Click here for the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital website

Click here for the Anxiety Disorders Association of America website

Starting date: March 2006
Ending date: March 2011
Last updated: March 18, 2008