Social Anxiety Disorder is recognized as a prevalent, chronic and disabling condition (Schneier et al, 1992). Lifetime prevalence has been estimated at 13% in the National Comorbidity Survey (NCS (Magee et al, 1996)). The age of onset of Social Anxiety Disorder (SAD) is early, usually in the teenage years, and social, academic and vocational impairment are often severe (Schneier et al, 1992; Stein et al, 2000). Depression and alcohol abuse are common sequelae.~There is a need for more therapeutic agents for Social Anxiety Disorder. At this time, only Paxil (paroxetine), Zoloft (sertraline), Luvox CR (fluvoxamine maleate), and Effexor XR (venlafaxine) are approved. However, each of these agents helps only about 45-55% of a given sample. Furthermore, the majority of those considered responders after an acute trial are still clinically symptomatic. The same can be said for the most effective form of psychosocial treatment for social anxiety disorder, Cognitive Behavior Therapy (CBT) (Heimberg et al, 1998), and other effective drug treatments such as phenelzine (Liebowitz et al, 1992) and clonazepam (Davidson et al, 1993). In addition, all of the drug treatments found effective to date have troubling adverse effects such as weight gain, sexual dysfunction, physical dependency, or inducing tolerance that can make long term use difficult. Thus, additional treatments are needed for Social Anxiety Disorder.~Vraylar® should be helpful for patients with SAD. It is a partial agonist at D2 and D3 receptors with affinity as well for a variety of serotonin receptors including 5-HT1A, 5-HT 2A 5-HT 2C and 5-HT 7. While it has been most extensively studied for its antipsychotic and anti-manic properties, its serotonergic and dopaminergic receptor profile suggests it may also be helpful for anxiety states. Social Anxiety Disorder is an excellent area to assess a medication's anti-anxiety properties. The disorder's high prevalence makes study enrollment fairly straightforward. Its chronicity mitigates against placebo response, which has been in the 30% range in most placebo-controlled trials. The most commonly used rating instrument for SAD, the Liebowitz Social Anxiety Scale (LSAS), has demonstrated validity and reliability. Most striking is the consistency and reproducibility of results from one trial to the next with the same agent. Registration trials for Zoloft® were 2 for 2 positive, for Paxil® 3 for 3, and for Effexor® XR 5 for 5. Finally, medications found effective for SAD have also been shown to work in generalized anxiety disorder, suggesting SAD as a good indication for proof of concept studies to test a medication's antianxiety properties.
The proposed study is a 12 week double-blind, placebo-controlled trial to examine the efficacy, safety, and tolerability of Vraylar® (cariprazine) in the treatment of patients with Social Anxiety Disorder (SAD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Subjects will be randomized to one of two treatment arms (placebo or Vraylar® 1.5 mg/day) in a 1:1 ratio. The study will be done at a single clinical research site.