Social phobia was first described as a unique, diagnosable disorder in DSM-III (American Psychiatric Association 1980). From a historical perspective, the disorder has been recognized since the middle of the 19th century, when Casper described erythrophobia (Casper 1902). Marks (1970) separated social phobia from other types of anxiety, including agoraphobia and simple phobia; thus, he described a clinical picture very similar to the disorder known today as social phobia. W. S. Tseng et al. (1992) described a transcultural variant of social phobia, common in Japan, named taijiu-kyofu (meaning anthropophobia), in which the individuals had anxiety related to the fear of causing discomfort in those around them. Although acknowledgment of the social phobia syndrome has been present for this extended period, it was not until the last decade that a true research interest peaked. Thus, from a historical perspective, all the pharmacological treatments of social phobia are relatively new. In this post, we review the major pharmacological studies and clinical trials involving social phobia as a target disorder (Table Drugs studied in the treatment of social phobia).
TABLE Drugs studied in the treatment of social phobia
Monoamine oxidase inhibitors (MAOIs) (irreversible)
Serotonin reuptake inhibitors
Buspirone, the novel anxiolytic, has also been studied in the treatment of social phobia. This drug’s proposed site of pharmacological activity is the 5-HT1A receptor, where it functions as an agonist. In prior studies, buspirone has shown efficacy in the treatment of generalized anxiety disorder (). Given its effectiveness in generalized anxiety disorder, investigators have started to look at buspirone’s utility in social phobia. Two trials have been reported looking at this drug in the treatment of social phobia.
Munjack et al. (1991) conducted a pilot study of buspirone in the treatment of social phobia. Subjects meeting DSM-IV criteria for social phobia were entered into an 8-week, open-label trial. Buspirone was started at 5 mg twice a day and increased by 5 mg every 2-3 days to a maximum dosage of 60 mg/day, or until side effects prevented further dose escalation. Of the 17 subjects entered in this study, 11 completed it. The 6 dropouts resulted from lack of responsiveness, adverse effects, inability to attend appointments, and a loss to follow-up. At week 6, of the 11 subjects completing the trial, 5 reported “a little” and 6 endorsed “moderate” change in their symptomatology. At the end of week 8, two subjects reported “a little,” 5 noted “moderate,” and 4 endorsed “marked” improvement. Although the global measures demonstrated the above results, instruments used to measure the features specific to social phobia demonstrated mixed results.
The use of buspirone in social phobia has also been investigated by Schneier et al. (1993). In this 12-week open trial, 21 patients who met DSM-IV criteria for social phobia and did not display a response during a 1-week placebo runin, went on to receive buspirone. The drug was initiated at 5 mg three times a day and was increased by 5 mg/day every 3 days to a maximum dosage of 60 mg/day or until side effects prevented further dose increases. Seventeen patients completed the trial. At the end of week 12, 8 (47%) of the 17 subjects were rated as “much” to “very much” improved on the Clinical Global Impression Scale (). Of those subjects tolerating doses of 45 mg/day or more, 67% (9/12) were at least “much improved.”
The results of these two open trials suggest that buspirone may at best have modest efficacy in the treatment of social phobia. These studies were limited by the open-label format and duration, given the findings of studies of other agents. Further studies are warranted to investigate the use of this agent in a controlled, blinded fashion. However, given the modest results and limited side-effect profile, some clinicians may want to add buspirone to their list of drugs given trials with patients with social phobia. Recommendations for use would be based on the similar study designs of the reported two trials, suggesting that buspirone should be started at 5 mg two to three times a day and increased by 5 mg/day to a dose of 45-60 mg.
A brief case report by Emmanuel et al. (1991) describes one patient with depression and social phobia who responded to bupropion, an aminoketone antidepressant with noradrenergic and dopaminergic effects. We are unaware of any further studies with this drug, which could shed light on the utility of this drug in the treatment of social phobia.
Ondansetron, a 5-HT3 antagonist, was the subject of a multicenter, double-blind, randomized, placebo-controlled clinical trial. Two hundred seventy-five subjects, meeting DSM-IV criteria for social phobia and completing a 1 -week, single-blind placebo run-in trial, were treated with ondansetron 0.25 mg twice a day or placebo for 10 weeks. On the primary efficacy variable, the Duke Brief Social Phobia Scale, the ondansetron treatment group demonstrated a statistically significant difference from the placebo group. Supportive efficacy variables also displayed statistical trends in favor of ondansetron over placebo (). The effect size was nonetheless small, and it is unclear whether this drug has competent therapeutic activity in social phobia. However, if the drug is proven to be effective, its unique 5-HT3 antagonist effect could help us understand the pathophysiology of the disorder.
As with the rationale for beta-blockers in the treatment of social phobia, clonidine hydrochloride, an a-adrenergic agonist, has been used in an attempt to target the physiological symptoms of the disorder. In a case report by Goldstein (1987), one subject with social phobia who experienced a primary symptom of blushing was treated with clonidine 0.1 mg twice a day after trials with alprazolam, phenelzine, and propranolol failed to provide symptom relief. The patient reported a dramatic decrease in the frequency and intensity of blushing episodes after 1 week of treatment. At 4-month follow-up, his symptoms remained well controlled and he denied any side effects.
Questions For Treatment And Research
Pharmacotherapy can effectively and rapidly reduce the symptoms and enable the individual with social phobia to function more effectively. However, several issues remain, including the algorithm by which treatment sequence is determined. Our experience suggests that clonazepam is a particularly effective drug, but the concerns of benzodiazepine use make many people uncomfortable. We do not know yet whether the much-used SSRIs or the selective and reversible MAOIs are as good. How long should pharmacotherapy be continued, and is relapse lower as cognitive-behavior therapy is added? More complex cases of social phobia, comorbid with depression, other anxiety disorders, alcohol abuse, or severe avoidant features are harder to treat and do not fare as well long term. How can such individuals be helped? To these practical questions, we can add the questions of mechanism: how do treatments work, can magnetic resonance studies illuminate their effects, and can some selective, effective, and better-tolerated drugs be developed? To current researchers in anxiety and clinicians we pose these questions.