Quetiapine as monotherapy for social anxiety disorder: A placebo-controlled study

Abstract

Social anxiety disorder (SAD) is one of the most common anxiety disorders. Reports have suggested an effect of the atypical antipsychotic quetiapine in anxiety disorders. Given these considerations, we conducted a controlled trial of quetiapine monotherapy in SAD. Fifteen patients were randomized to quetiapine (up to 400 mg/day) or placebo for 8 weeks. The Brief Social Phobia Scale (BSPS) and the Clinical Global Impression of Improvement Scale (CGI-I) were the primary outcome measures, while the Social Phobia Inventory (SPIN) and the Sheehan Disability Inventory (SDI) were secondary measures. There was no significant difference on the BSPS score at endpoint between the quetiapine and placebo groups. There was a significant time effect but not a significant time × treatment group interaction, indicating that both the quetiapine and placebo patients did better over the course of the trial. 20% of the quetiapine patients had a 50% or greater drop in BSPS score at the end of the trial compared to baseline, while 0% had such a drop in the placebo group. There was no significant difference in responders (CGI-I score of 1 or 2) versus non-responder (CGI-I score of 3 or more) across the groups. However, 40% of quetiapine patients and 0% of the placebo patients showed much or very much improvement on the CGI-I. The Number Needed to Treat (NNT) to be a responder on the CGI-I was 3. Significant time effects were noted for the SPIN and SDI, as well as a significant time × treatment effect in favor of quetiapine on the SPIN. Additionally, quetiapine showed a large effect size on the SPIN.

Introduction

Social anxiety disorder (SAD) is characterized by overwhelming fear and avoidance of social or performance situations. It is one of the most common anxiety disorders (Magee et al., 1996) and the third most common psychiatric disorder in the United States, with a lifetime prevalence of up to 16% in the general population (Hidalgo et al., 2001).

The disorder typically begins in adolescence and has a lifelong course (Kessler et al., 1998, Schneier et al., 1992). Socioeconomic disadvantages, impaired quality of life, and decreased treatment seeking are common among patients with SAD (Gross et al., 2005). In addition, high rates of comorbidity with other psychiatric disorders including depression and alcohol abuse, as well as general medical illnesses, are frequently reported (Stein et al., 1998).

There are data from controlled trials that show paroxetine (Stein et al., 1998), fluvoxamine (Stein et al., 1999), sertraline (Van Ameringen et al., 2001), phenelzine (Gelernter et al., 1991), moclobemide (Davidson et al., 1993), alprazolam (Gelernter et al., 1991), clonazepam (Davidson et al., 1993), and gabapentin (Pande et al., 1999) as well as cognitive behavioral therapy (CBT) (Heimberg et al., 1998) have some efficacy for treatment of SAD. Current preferred treatments include CBT and the use of selective serotonin reuptake inhibitors (SSRIs) (Davidson et al., 2004). However, response rates leave much room for improvement. One meta-analysis shows a moderate mean SSRI effect size of 0.65 (Blanco et al., 2003). Meta-analyses with CBT also show a moderate mean effect size of 0.72 (Rodebaugh et al., 2004). One direct blinded comparison of fluoxetine, CBT, combination therapy, and placebo found a maximal response rate of 54% for active treatment, compared to 32% for placebo (Davidson et al., 2004). Overall, the response of SAD to available treatments is modest, with considerable symptom residue and low rates of remission.

There is clearly a need for additional therapies for SAD. Atypical antipsychotics have shown some evidence for efficacy in anxiety symptoms in schizophrenia (Tollefson et al., 1998). Additionally, these agents have now been evaluated for treatment of anxiety disorders such as posttraumatic stress disorder (PTSD) and obsessive compulsive disorder (OCD) (Atmaca et al., 2002). There is also evidence to suggest patients with SAD have lower dopaminergic D2 receptor binding potential (Schneier et al., 2000) and decreased dopaminergic reuptake site densities in the striatum (Tiihonen et al., 1997). As such, antidopaminergic agents (such as antipsychotics) may potentially be useful in SAD. To our knowledge, one controlled pilot study has shown some efficacy for atypical antipsychotic monotherapy, with olanzapine, for SAD (Barnett et al., 2002).

Quetiapine is an atypical antipsychotic with greater serotinergic than dopaminergic effects; quetiapine acts on 5HT2A, 5HT6, 5HT7, H1, alpha-1, alpha-2, and D2 receptors (Stahl, 2000). It has reported anxiolytic properties; one study has found quetiapine to be effective against anxiety in long-term treatment of patients with schizophrenia (Kashmper, 2004) while another showed significant improvement in anxiety with bipolar patients (Calabrese et al., 2005). There is one open-label trial supporting the use of quetiapine in SAD that we are aware of (Schutters et al., 2005).

To our knowledge, there are no controlled studies of quetiapine as monotherapy for SAD. Our purpose was to study quetiapine in a double-blind, placebo-controlled pilot trial for SAD. The primary hypothesis is that monotherapy with quetiapine will be more effective than placebo in decreasing symptoms of SAD.