Duloxetine for Social Anxiety Disorder: Prediction of Long Term Outcome

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and efficacy of duloxetine for the treatment of social anxiety disorder.

Detailed Description
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An expanding body of clinical experience and controlled trials has established the efficacy of serotonin selective reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine, for the treatment of social anxiety disorder, with paroxetine, sertraline and venlafaxine extended-release (XR), which are FDA approved for this indication. The newest SNRI, duloxetine, has been shown to be effective at doses of 60mg/day to 120mg/day for anxiety associated with depression, and is anticipated to be a broad spectrum agent for mood and anxiety disorders (Dunner, Goldstein, Mallinckrodt, Lu, & Detke, 2003). However, no data on the efficacy of duloxetine for Social Anxiety Disorder, nor guidance regarding time to response or predictors of response, is yet available. These questions are the focus of this proposal. This is a two phase, 24-week research study in which participants who remain symptomatic at the end of one phase (6 weeks) enter into the next phase. In phase I, all participants receive 60mg/day of duloxetine (Cymbalta) for 6 weeks. Participants who continue to have anxiety symptoms will enter the 18-week Phase II, in which they continue taking 60 mg/day of duloxetine and they will also be randomly assigned (by chance, like a flip of a coin) to receive either an additional 60mg/day of duloxetine or placebo (contains no active medication).

Official Title
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Duloxetine for Social Anxiety Disorder: Prediction of Long Term Outcome

Conditions
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Anxiety Disorder

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients > 18 years of age with a primary psychiatric diagnosis of generalized social anxiety disorder as defined by DSM-IV criteria and an LSAS score > 50. Physical examination, electrocardiogram, and laboratory findings without clinically significant abnormalities. Willingness and ability to comply with the requirements of the study protocol. Exclusion Criteria: Patient has a history of intolerance or lack of response to a treatment trial of duloxetine at highest tolerated dose (<120mg/day). Patients with acute narrow angle glaucoma. 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). Concurrent use of other psychotropic medications. Patients must discontinue regular benzodiazepine or antidepressant therapy at least one week (5 weeks for fluoxetine) prior to baseline. Concomitant beta-blockers are proscribed unless prescribed for a medical indication (e.g., hypertension, at a stable daily dose for > 1 month). Patients with a history of failure to satisfactorily respond to >2 prior adequate treatment trials. Significant personality dysfunction likely to interfere with study participation. Serious medical illness or instability for which hospitalization may be likely within the next year. Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood, were isolated, and did not recur in adulthood. Concurrent psychotherapy initiated within 2 months of baseline is prohibited. Ongoing psychotherapy of any duration directed specifically toward treatment of the social anxiety disorder is excluded. Prohibited psychotherapy includes cognitive behavioral therapy or psychodynamic therapy that focuses on exploring specific, dynamic causes of the phobic symptomatology and provides skills for their management. General supportive individual, couples, or family therapy greater than 2 months duration is acceptable. Diagnosis of any of the following mental disorders as defined by the DSM-IV: a lifetime history of schizophrenia or any other psychosis, mental retardation, organic medical disorders or bipolar disorder; eating disorders in the past 6 months; alcohol or substance abuse in the past 3 months or dependence within the past 6 months. Entry of patients with major depression, dysthymia, panic disorder, generalized anxiety disorder, post-traumatic stress disorder or obsessive-compulsive disorder will be permitted if the social anxiety disorder 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Duloxetine 60mg + Placebo for 18 Weeks<br>In Phase 2 participants were randomized to 60mg Duloxetine + Placebo or 120mg Duloxetine. | Drug: Duloxetine<br>* 60 mg duloxetine 1x per day<br>* Other names: Cymbalta;Drug: Placebo<br>* 60mg placebo 1x per day<br>|
| Active Comparator: Duloxetine 120mg for 18 Weeks<br>In Phase 2 participants were randomized to 60mg Duloxetine + Placebo or 120mg Duloxetine. | Drug: Duloxetine<br>* 60 mg duloxetine 1x per day + 60mg duloxetine 1x per day<br>* Other names: Cymbalta;|
| Active Comparator: Duloxetine 60mg/day for 6 Weeks<br>In Phase 1 all participants entered an open trial. | Drug: Duloxetine<br>* 60 mg duloxetine 1x per day<br>* Other names: Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety Symptoms as Assessed by Liebowitz Social Anxiety Scale | The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety. The LSAS contains three total scores: 1) total fear score (0-72), 2) total avoidance score(0-72), 3) and total overall score (0-144). Suggested interpretations: 55-65 Moderate social phobia, 65-80 Marked social phobia, 80-95 Severe social phobia, Greater than 95 - Very severe social phobia. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI-S | The Clinician Global Impression-Severity Scale (CGI-S) is a clinician-rated instrument used to assess global severity of symptoms (Guy, 1976). The CGI ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline collected for Phase 1 at week 0 and for Phase 2 at week 6. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SNRI, social anxiety disorder, social phobia, duloxetine, serotonin norepinephrine reuptake inhibitor, double blind