Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mark H. Pollack, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00282828
First received: January 25, 2006
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Social Phobia
Drug: Sertraline
Drug: Venlafaxine
Drug: Placebo
Drug: Clonazepam
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improving Outcomes in Pharmacotherapy of Social Phobia

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Rates of Remission (LSAS≤30) After 12 Weeks of Randomized Treatment During Phase II, Among Phase I Non-responders [ Time Frame: Measured at Week 22 (Endpoint) ] [ Designated as safety issue: No ]
    The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.


Secondary Outcome Measures:
  • Post-treatment Social Phobia Severity as Defined by Endpoint LSAS Scores [ Time Frame: Change from Week 10 to Week 22 ] [ Designated as safety issue: No ]
    The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). We analyzed the overall change in LSAS (last Phase II LSAS minus Week 10 LSAS). Higher numbers reflect greater drops in social anxiety disorder severity. Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.


Enrollment: 397
Study Start Date: March 2006
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sertraline & Clonazepam

Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of clonazepam up to 3.0mg per day.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 0.5mg of clonazepam per day in order to remain in the study.

Drug: Sertraline
Other Name: Sertraline
Drug: Clonazepam
Other Name: Clonazepam
Experimental: Venlafaxine

Phase I non-responders randomized to this group switched to venlafaxine with flexible titration up to 225 mg per day.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 75 mg venlafaxine per day in order to remain in the study.

Drug: Venlafaxine
Other Name: Venlafaxine
Experimental: Sertraline & Placebo

Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of placebo.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 1 capsule of placebo per day in order to remain in the study.

Drug: Sertraline
Other Name: Sertraline
Drug: Placebo
Other Name: Placebo

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 22.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, with the exception of psychostimulants to treat ADHD; 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282828

Locations
United States, California
University of California San Diego
La Jolla, California, United States, 92093
United States, Massachusetts
Center for Anxiety and Traumatic Stress Disorders
Boston, Massachusetts, United States, 02116
Canada, Ontario
McMaster University Medical Centre Anxiety Disorders Clinic
Hamilton, Ontario, Canada, L8N 3Z5
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Mark H. Pollack, MD Massachusetts General Hospital
Principal Investigator: Murray B. Stein, MD, MPH University of California San Deigo
Principal Investigator: Michael Van Ameringen, MD, FRCPC Anxiety Disorders Clinic McMaster University Medical Centre
  More Information

Additional Information:
No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mark H. Pollack, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00282828     History of Changes
Other Study ID Numbers: R01 MH70919, R01MH070919, PA-01-123, DSIR 83-ATAS
Study First Received: January 25, 2006
Results First Received: April 22, 2013
Last Updated: August 8, 2013
Health Authority: United States: Federal Government
Canada: Health Canada

Keywords provided by Massachusetts General Hospital:
Social Anxiety Disorder
Pharmacotherapy
Genetics
Treatment Refractory

Additional relevant MeSH terms:
Anxiety Disorders
Mental Disorders
Sertraline
Venlafaxine
Clonazepam
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Anticonvulsants
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on September 16, 2014