The purpose of this study is to examine the safety and efficacy of duloxetine for the
treatment of social anxiety disorder.
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
- 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 >
- Physical examination, electrocardiogram, and laboratory findings without clinically
- Willingness and ability to comply with the requirements of the study protocol.
- 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
- 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.