Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study. Psychopharmacological treatment of social phobia; a double blind placebo controlled study with fluvoxamine. Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine. Psychopharmacological treatment of social phobia: clinical and biochemical effects of brofaromine, a selective MAO-A inhibitor. A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder. Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial. Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group. Paroxetine for social anxiety and alcohol use in dual-diagnosed patients. Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study. Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder. Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome. Paroxetine in the treatment of generalized social phobia: open-label treatment and double-blind placebo-controlled discontinuation. Moclobemide in social phobia: a controlled dose-response trial. Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study. Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial. Treatment of social phobia with gabapentin: a placebo-controlled study. Social phobia: the clinical efficacy and tolerability of the monoamine oxidase -A and serotonin uptake inhibitor brofaromine. A double-blind placebo-controlled study. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study. Discontinuation of clonazepam in the treatment of social phobia. The assessment and treatment of performance anxiety in musicians. The International Multicenter Clinical Trial Group on Moclobemide in Social Phobia. Moclobemide in social phobia. A double-blind, placebo-controlled clinical study. Placebo-controlled trial of moclobemide in social phobia. Sertraline for social phobia: a double-blind, placebo-controlled crossover study. Treatment of social phobia with clonazepam and placebo. Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study. Phenelzine vs atenolol in social phobia. A placebo-controlled comparison. Paroxetine in social anxiety disorder: a randomized placebo-controlled study. Prevention of relapse in generalized social phobia: results of a 24-week study in responders to 20 weeks of sertraline treatment. Social phobia: a comparison of behavior therapy and atenolol. Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia. Effect of pindolol on stress-related disturbances of musical performance: preliminary communication. Efficacy of olanzapine in social anxiety disorder: a pilot study. Brofaromine for social phobia: a multicenter, placebo-controlled, double-blind study.
The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia.
                In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety.
                Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated.
                The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone. Previous studies have shown selective and nonselective monoamine oxidase inhibitors (MAOIs) to be effective in the treatment of social phobia. In this study we investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Thirty patients with social phobia (DSM-IIIR) were treated with the SS-RI fluvoxamine (150 mg daily) using a 12-week double-blind placebo controlled design. A substantial improvement was observed in seven (46%) patients on fluvoxamine and in one (7%) on placebo. Statistically significant effects were seen on measures of social anxiety and general (or anticipatory) anxiety in patients treated with fluvoxamine compared with placebo. The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance. It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia, suggesting that serotonergic mechanisms might be implicated in social anxiety. In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs. There is circumstantial evidence that antidepressants, particularly monoamine oxidase inhibitors (MAOIs) and beta-blockers, may have some beneficial effects in social phobia. In this study 30 patients with social phobia (DSM-IIIR) were treated with the selective and reversible MAO-A inhibitor brofaromine, using a 12-week double-blind placebo controlled design. A clinical relevant improvement was seen in 80% of the patients treated with brofaromine (150 mg daily). A significant improvement was found on measures of social anxiety, phobic avoidance, general (or anticipatory) anxiety and interpersonal sensitivity in patients on brofaromine, but not on placebo. Biochemical measurements revealed a decrease in turnover of noradrenaline, serotonin and dopamine as assessed by the plasma metabolite levels, and an increase in nocturnal release of melatonin. Most prominent side-effect was middle sleep disturbance. No changes in blood pressure were observed. During a follow-up period of 12 weeks a further improvement was found in patients treated with brofaromine. This multicenter, double-blind, placebo-controlled study was carried out to determine the effectiveness and safety of various daily dosages of paroxetine for the treatment of generalized social anxiety disorder.
                A 1-week, single-blind, placebo run-in was followed by 12 weeks of double-blind treatment. 384 eligible patients meeting DSM-IV criteria for social anxiety disorder were randomly assigned to receive paroxetine, 20 (N = 97), 40 (N = 95), or 60 mg (N = 97), or placebo (N = 95) once daily in a 1:1:1:1 ratio. Primary efficacy variables included mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and proportion of patients exhibiting a therapeutic response (defined as a Clinical Global Impressions-Global Improvement scale [CGI-1] score of 1 or 2).
                In the last-observation-carried-forward analyses, patients treated with paroxetine, 20 mg/day, had significantly greater improvement on mean LSAS total scores compared with those receiving placebo (p < .001), while the incidence of responders, based on the CGI-I rating, was significantly greater with paroxetine, 40 mg/day, than with placebo (p = .012). Patients treated with paroxetine, 20 and 60 mg, also had significantly better responses on the social item of the Sheehan Disability Scale than did patients treated with placebo (p < .019). The completer analyses showed a significant difference between the placebo group and the 20-mg and 40-mg paroxetine groups on LSAS total score and rate of response (p < or = .006). There were no serious adverse experiences attributed to paroxetine treatment.
                Paroxetine, 20 mg/day, is an effective and safe treatment for patients with generalized social anxiety disorder and significantly improves social anxiety, avoidance of social interactions, social disability, and overall clinical condition. Further data analyses are needed to determine whether more specific guidelines for paroxetine dosage escalation in social anxiety disorder can be drawn. Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase. Preliminary studies have suggested that paroxetine may be effective in social phobia/social anxiety disorder.
                To assess the efficacy and tolerability of paroxetine in the acute (12-week) treatment of social phobia.
                Two-hundred and ninety patients with social phobia were assigned randomly to paroxetine (20-50 mg/day flexible dose) or placebo for 12 weeks of double-blind treatment. Primary efficacy outcomes were the Liebowitz Social Anxiety Scale (LSAS) total score (patient-rated) and the Clinical Global Impression (CGI) scale global improvement item. The secondary efficacy variables included CGI scale severity of illness score and the patient-rated Social Avoidance and Distress Scale.
                Paroxetine produced a significantly greater reduction in LSAS total score (mean change from baseline: -29.4 v. -15.6; P < or = 0.001) and a greater proportion of responders (score < or = 2 on CGI global improvement) (65.7% v. 32.4%; P < 0.001) compared with placebo at the end of the 12-week study period. Both primary efficacy variables were statistically significant compared with placebo from week 4 onwards. Paroxetine was generally well tolerated.
                Paroxetine is an effective, well-tolerated treatment for patients with social phobia. The objective of this study was to compare the efficacy and tolerability of paroxetine to matched placebo in adults with co-occurring social anxiety disorder and alcohol use disorder. Outcome measures included standardized indices of social anxiety and alcohol use. Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d and increased to a target dose of 60 mg/d. There was a significant effect of treatment group on social anxiety symptoms, where patients treated with paroxetine improved more than those treated with placebo on both the Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05). On alcohol use, there was not a significant effect of treatment on quantity/frequency measures of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo patients were improvers on drinking, P < or = 0.05). This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in individuals with comorbid alcohol problems, and positive treatment effects can be seen in as little as 8 weeks. Further study is warranted to investigate its utility in helping affected individuals reduce alcohol use.
                Copyright 2001 Wiley-Liss, Inc. The efficacy of selective serotonin reuptake inhibitors in the acute treatment of social anxiety disorder (social phobia) is well established.
                To evaluate whether the efficacy of paroxetine hydrochloride in this disorder is maintained in the long term.
                This was a placebo-controlled multicenter study comprising a single-blind acute treatment phase (12 weeks) and a randomized, double-blind maintenance treatment phase (24 weeks) for patients who had responded to paroxetine during the acute phase. Four hundred thirty-seven adult patients with social anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, code 300.23) entered the acute phase, and 323 continued into the maintenance phase (162 paroxetine and 161 placebo). The principal outcome measure was the proportion of patients relapsing during the maintenance phase.
                Two hundred fifty-seven patients completed the study (136 paroxetine-treated and 121 placebo-treated patients). Significantly fewer patients relapsed in the paroxetine group than in the placebo group (14% vs 39%; odds ratio, 0.24; 95% confidence interval, 0.14-0.43; P<.001). At the end of the study, a significantly greater proportion of patients in the paroxetine group showed improvement as shown on the Clinical Global Impression global improvement rating compared with the placebo group (78% vs 51%; odds ratio, 3.66; 95% confidence interval, 2.22-6.04; P<.001). Compared with placebo, paroxetine treatment significantly (P<.001) improved the symptoms of social anxiety as shown on the Liebowitz Social Anxiety Scale, Social Phobia Inventory, Sheehan Disability Scale, Symptom Checklist-90 score, and EuroQol visual analogue scale, indicating decreased disability and increased well-being. Paroxetine was well tolerated.
                Paroxetine is an effective long-term treatment for social anxiety disorder. Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder. This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy (CBGT) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia.
                One hundred thirty-three patients from 2 sites received 12 weeks of CBGT, phenelzine therapy, pill placebo administration, or educational-supportive group therapy (an attention-placebo treatment of equal credibility to CBGT). The "allegiance effect," ie, the tendency for treatments to seem most efficacious in settings of similar theoretical orientation and less efficacious in theoretically divergent settings, was also examined by comparing responses to the treatment conditions at both sites: 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment. RESULTs: After 12 weeks, phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition. However, response to phenelzine therapy was more evident after 6 weeks, and phenelzine therapy was also superior to CBGT after 12 weeks on some measures. There were few differences between sites, suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances.
                After 12 weeks, both phenelzine therapy and CBGT were associated with marked positive response. Although phenelzine therapy was superior to CBGT on some measures, both were more efficacious than the control conditions. More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect. We conducted an 11-week forced-escalation open-label study of paroxetine in the treatment of 36 patients with generalized social phobia. At the mean dosage of 47.9 +/- 6.2 mg/day, 23 of 30 completers (77%) were deemed responders on the basis of a clinician rating of either "very much improved" or "much improved" on the Clinical Global Impressions scale. Duke Social Phobia Scale ratings declined from 35.5 +/- 13.1 at baseline to 19.7 +/- 17.4 at week 11 (p < 0.0005), and Liebowitz Social Anxiety Scale ratings declined from 75.1 +/- 25.4 at baseline to 37.2 +/- 32.5 at week 11 (p < 0.0005). Sixteen responders were randomized to an additional 12 weeks of either paroxetine (with no dosage change) or placebo (after a taper period) on a double-blind basis. To the best of our knowledge, this is the first controlled medication-discontinuation study in social phobia. One of eight patients randomized to continue paroxetine relapsed versus five of eight patients randomized to placebo. These findings call for a double-blind, placebo-controlled treatment study of paroxetine in generalized social phobia. They also suggest that relapse rates are high if medication is discontinued early and that further study is needed to determine (1) the optimal duration of maintenance pharmacotherapy for social phobia and (2) if specific psychotherapeutic interventions before medication discontinuation may prevent relapse. Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed. The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder).
                In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale.
                The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe.
                These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia. The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use.
                To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia.
                Twelve-week, multicenter, randomized, double-blind trial.
                Thirteen centers across the United States and 1 in Canada.
                Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment.
                After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment.
                Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score.
                Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine.
                Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques. A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of social phobia. Sixty-nine patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 900 and 3,600 mg daily in three divided doses) or placebo for 14 weeks. A significant reduction (p < 0.05) in the symptoms of social phobia was observed among patients on gabapentin compared with those on placebo as evaluated by clinician- and patient-rated scales. Results were similar for the intent-to-treat and week-2 completer populations. Adverse events were consistent with the known side effect profile of gabapentin. Dizziness (p = 0.05), dry mouth (p = 0.05), somnolence, nausea, flatulence, and decreased libido occurred at a higher frequency among patients receiving gabapentin than among those receiving placebo. No serious adverse events or deaths were reported. On the basis of these limited data, it seems that gabapentin offers a favorable risk-benefit ratio for the treatment of patients with social phobia. Further studies are required to confirm this effect and to determine whether a dose-response relationship exists. Seventy-seven patients with a primary diagnosis of social phobia (DSM-III-R) were randomized to treatment with the reversible and selective monoamine oxidase type A inhibitor brofaromine (n = 37) or placebo (n = 40) for 12 weeks in a double-blind trial. A fixed dose of 150 mg/day or a matching placebo was given after a 2-week dose titration phase. Patients with additional diagnoses of simple phobia, generalized anxiety disorder, dysthymia or major depressive disorder currently in remission were accepted. Patients with other Axis I mental disorders were excluded. In the brofaromine group, 78% of the patients scored much or very much improved on the Clinical Global Impression scale compared with 23% in the placebo group. The anxiety and avoidance scores on the Liebowitz Social Anxiety Scale (LSAS) were significantly reduced in favor of brofaromine. The clinical effects were not significantly correlated with the plasma concentration of brofaromine. After 12 weeks the brofaromine group scored significantly lower than the placebo group on a core depression part of the Montgomery-Asberg Depression Rating Scale. After 12 weeks of treatment the brofaromine group had significantly higher total scores on the LSAS than an age- and gender-matched group of healthy controls. The brofaromine group improved further during 9-month follow-up treatment period, whereas 60% of the placebo responders who continued long-term treatment relapsed. The most common side effects in the brofaromine group were sleep disturbances, dry mouth and nausea. The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia.
                Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale.
                In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study.
                Sertraline is an effective treatment for patients with generalized social phobia. The objective of the study was to examine the efficacy of fluoxetine in social phobia. Sixty subjects were randomly assigned to 14 weeks of double-blind therapy with either fluoxetine or placebo. Dose was fixed at 20 mg for fluoxetine during the first 8 weeks of double-blind treatment; during the final 6 weeks, the dose could be increased every two weeks by 20 mg to a maximum of 60 mg/day. An intentto-treat analysis was used. A significant change from baseline to endpoint was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale. However, no significant difference was found between fluoxetine and placebo. The change for fluoxetine was somewhat lower than that found with other selective serotonin reuptake inhibitors, whereas the placebo response was greater. Fluoxetine failed to separate from placebo in this trial. It is unknown whether a larger dose for longer duration would have yielded separation from placebo. A higher than usual placebo response rate was found. Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper. Performance anxiety in musicians may be severe enough to require intervention but has been the subject of relatively little clinical research. The authors' objectives were to describe the results of a comprehensive clinical and laboratory assessment and to perform a double-blind, placebo-controlled study comparing buspirone, cognitive-behavior therapy, and the combination of these treatments for performance anxiety.
                Ninety-four subjects were recruited by mass media announcements and were seen in a university-based outpatient psychiatric clinic. Assessments were 1) questionnaires for all 94 subjects, 2) diagnostic interview of 50 subjects, and 3) laboratory performance of 34 subjects. Treatment conditions were 1) 6 weeks of buspirone, 2) 6 weeks of placebo, 3) a five-session, group cognitive-behavior therapy program with buspirone, or 4) the cognitive-behavior therapy program with placebo. Treatment outcome measures included subjective anxiety ratings and heart rate measures during a laboratory performance, a questionnaire measure of performance confidence, and a blind rating of musical performance quality.
                All subjects fulfilled criteria for DSM-III-R social phobia. Of the 15 full-time professional musicians, ten had tried propranolol and three had stopped performing. Most of the subjects had substantial anxiety and heart rate increases during laboratory speech and musical performances. Cognitive-behavior therapy resulted in statistically significant reductions in subjective anxiety, improved quality of musical performance, and improved performance confidence. Buspirone was not an effective treatment.
                Cognitive-behavior therapy is a viable treatment approach for performance anxiety in musicians. The primary objectives of this large multicenter study (n = 578) were to determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the treatment of social phobia. A double-blind fixed-dose parallel group study was conducted to compare the two different doses of moclobemide to placebo. After a 1-week placebo run-in period, patients were randomly assigned to one of the three treatment groups to receive the test compound for a 12-week period. Assessments were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12. There were consistent, reliable and clinically meaningful drug effects and indications of a dose-response relationship. Statistical analysis of the results at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and statistically significantly superior to placebo. The 300 mg dose also showed better efficacy than placebo on all measures of efficacy, and about half of them were statistically significantly different from placebo. Moclobemide was well tolerated. Adverse events, except for insomnia, were neither dose-related nor were there significant drug-placebo differences. The results indicate that 600 mg of moclobemide per day given b.i.d. is effective in social phobia, reducing the symptoms and the impairment associated with the disorder. The compound is well tolerated and safe. Moclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.
                Seventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.
                Intention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.
                Moclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small. The authors examined the efficacy of sertraline in the treatment of social phobia.
                In a double-blind crossover study, 12 outpatients were randomly assigned to 10 weeks of sertraline (50-200 mg/day, flexible dosing) and 10 weeks of placebo.
                A statistically significant improvement in scores on the Liebowitz Social Anxiety Scale was found with sertraline but not with placebo. There was no significant difference between scores obtained with computer- and clinician-administered versions of the Liebowitz Social Anxiety Scale, and the majority of patients preferred to be interviewed by the computer.
                Sertraline seems a safe and effective treatment for social phobia, and computer administration may be a preferable mode of assessment with socially phobic patients. Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects. Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults.
                After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score </= 2. Data were collected in 2000 and 2001.
                211 patients were randomly assigned to sertraline (intent-to-treat [ITT] sample, 205), and 204 patients, to placebo (ITT sample, 196). At week 12, sertraline produced a significantly greater reduction in LSAS total score compared with placebo (mean last-observation-carried-forward [LOCF] change from baseline: -31.0 vs. -21.7; p =.001) and a greater proportion of responders (CGI-I score </= 2: 55.6% vs. 29% among week 12 completers and 46.8% vs. 25.5% in the ITT-LOCF sample; p <.001 for both comparisons). Sertraline was well tolerated, with 7.6% of patients discontinuing due to adverse events versus 2.9% of placebo-treated patients.
                The results of the current study confirm the efficacy of sertraline in the treatment of severe social anxiety disorder. Seventy-four patients who met DSM-III criteria for social phobia completed 8 weeks of double-blind, randomly assigned treatment with the monoamine oxidase inhibitor phenelzine sulfate, the cardioselective beta-adrenergic blocker atenolol, or placebo. The overall response rates were 64% for phenelzine, 30% for atenolol, and 23% for placebo. Phenelzine was widely superior to both atenolol and placebo on independent rater analyses and, to a lesser extent, on self-report, with no significant differences between atenolol and placebo. At the end of 16 weeks, phenelzine was still significantly superior to placebo, while atenolol showed an intermediate response that did not differ significantly from either of the other treatments. Patients with generalized social phobia constituted 76% of the sample, and they were preferentially responsive to phenelzine. The small size of the discrete social phobic sample precluded separate outcome analyses for this subtype. Overall, the findings support the responsivity of social phobia to monoamine oxidase inhibitors. The aim of this study was to evaluate the utility of paroxetine treatment in social anxiety disorder.
                Previously undiagnosed and untreated subjects with social anxiety disorder (generalized social phobia) were selected from among responders to a newspaper advertisement. They were randomized to double-blind treatment with paroxetine 20-50 mg daily or placebo for 3 months. Outcome measures were self-rated social anxiety and avoidance behaviour, and clinician-rated global assessment of improvement.
                Significant differences in efficacy between treatments (intent-to-treat analysis: 44 subjects on paroxetine and 48 subjects on placebo) were noted after 4-6 weeks, increasing through the treatment period in the paroxetine group. Nine subjects on paroxetine and 3 subjects on placebo discontinued the treatment due to adverse events. Sexual side-effects were noted by 18 subjects on paroxetine and 4 subjects on placebo.
                Paroxetine was effective in alleviating symptoms and avoidance behaviour in social anxiety disorder. The aim of this study was to evaluate the efficacy, tolerability, and effects on quality of life of sertraline, a selective serotonin reuptake inhibitor, in the prevention of relapse of generalized social phobia. Fifty adult outpatients with generalized social phobia who were rated much or very much improved on the Clinical Global Impression Scale of Improvement (CGI-I) after 20 weeks of sertraline treatment (50-200 mg/day) were randomly assigned in a one-to-one ratio to either continue double-blind treatment with sertraline or immediately switch to placebo for another 24 weeks. The initial 20-week study was placebo-controlled, and 15 responders to placebo also continued to receive double-blind placebo treatment in the continuation study. Eighty-eight percent of patients in the sertraline-continuation group and only 40% of patients in the placebo-switch and placebo-responder groups completed the study. In intent-to-treat endpoint analyses, 1 (4%) of 25 patients in the sertraline-continuation group and 9 (36%) of 25 patients in the placebo-switch group had relapsed at study endpoint (chi2 = 8.0, Fisher exact test, p = 0.01). The relative risk (hazards ratio) for relapse associated with placebo-switch relative to sertraline-continuation treatment was 10.2 (95% confidence interval, 1.3-80.7). Mean CGI-Severity, Marks Fear Questionnaire (MFQ) Social Phobia subscale, and Duke Brief Social Phobia Scale (BSPS) total scores were reduced by 0.07, 0.34, and 1.86 in the Sertraline-Continuation group and increased by 0.88, 4.09, and 5.99 in the Placebo-Switch group (all F > 5.3, p < 0.03), respectively. CGI-Severity, MFQ Social Phobia subscale, and BSPS scores also increased in the Placebo-Responder group. Discontinuations because of lack of efficacy were 4% in the sertraline-continuation group, 28% in the placebo-switch group (chi2 = 5.36, Fisher exact test, p = 0.049), relative to sertraline, and 27% in the placebo-responder group. Sertraline was effective in preventing relapse of generalized social phobia. Future research should assess whether improvements may be maintained or further increased by longer periods of treatment or through the addition of cognitive-behavioral techniques. Seventy-two social phobics were randomly assigned to behavioral (flooding) or drug treatment with atenolol or placebo. Treatment was administered over a 3-month period of time, and duration of treatment effects was determined at a 6-month follow-up assessment. Multiple measures of outcome were used, including self-report, clinician ratings (including assessment by independent evaluators), behavioral assessment, and performance on composite indexes. The results indicated that flooding consistently was superior to placebo, whereas atenolol was not. Flooding also was superior to atenolol on behavioral measures and composite indexes. Those subjects who improved during treatment maintained gains at the 6-month follow-up regardless of whether they received flooding or atenolol. The variability of outcome on different measures in social phobia research is discussed, and the need for broad-based treatment strategies to address the pervasive deficits associated with social phobia is noted. No controlled trial of treatment of generalised social phobia has been conducted in general practice.
                To examine the efficacy of sertraline or exposure therapy, administered alone or in combination in this setting.
                Study was of a randomised, double-blind design. Patients (n = 387) received sertraline 50-150 mg or placebo for 24 weeks. Patients were additionally randomised to exposure therapy or general medical care.
                Sertraline-treated patients were significantly more improved than non-sertraline-treated patients (chi(2)=12.53, P<0.001; odds ratio=0.534; 95% Cl 0.347-0.835). No significant difference was observed between exposure- and non-exposure-treated patients (chi(2)=2.18, P=0.140; odds ratio=0.732; 95% Cl 0.475-1.134). In the pairwise comparisons, combined sertraline and exposure (chi(2)=12.32; P<0.001) and sertraline (chi(2)=10.13; P=0.002) were significantly superior to placebo.
                Sertraline is an effective treatment for generalised social phobia. Combined treatment with sertraline and exposure therapy, conducted by the general practitioner, may enhance the treatment efficacy in primary care. The effect of 5 mg pindolol on stress-induced disturbances of performance were assessed in 30 professional musicians. An overall inverse relationship was found between anxiety and musical performance. Reduction in anxiety by administration of pindolol was associated with a subjective improvement in performance. A stress-related tachycardia and increase in systolic blood pressure were attenuated. Pindolol had no effect on peak flow measurements. Based on evidence suggesting anxiolytic properties of the atypical antipsychotic olanzapine, this study was conducted to evaluate whether olanzapine may be efficacious in treating social anxiety disorder (SAD). This study was an 8-week, double-blind, placebo-controlled evaluation of olanzapine as monotherapy in which 12 patients with the DSM-IV diagnosis of SAD were randomized to either olanzapine (n = 7) or placebo (n = 5). An initial dose of 5 mg/day was titrated to a maximum of 20 mg/day. Baseline to endpoint scores from the Brief Social Phobia Scale (BSPS), Social Phobia Inventory (SPIN), Liebowitz Social Anxiety Scale and Sheehan Disability Scale, as well as Clinical Global Impression-Improvement ratings, were compared for olanzapine versus placebo. Seven subjects completed all 8 weeks of the study, four in the olanzapine group and three in the placebo group. In the intent-to-treat analysis, olanzapine yielded greater improvement than placebo on the primary measures: BSPS (p = 0.02) and SPIN (p = 0.01). Both treatments were well tolerated, although the olanzapine group had more drowsiness and dry mouth. Olanzapine and placebo were both associated with negligible weight gain. Olanzapine was superior to placebo on the primary outcome measures in this preliminary study of SAD. Additional studies of olanzapine as a treatment for SAD are warranted. The safety and efficacy of brofaromine, a reversible and selective monoamine oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with social phobia. After a 1-week placebo washout, subjects were randomly assigned to 10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50). Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150 mg/day, depending on treatment response. Brofaromine produced a significantly greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from 81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41,p < 0.001, and from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine early terminators discontinued because of adverse experiences, as did 4 of the 17 placebo early terminators. Side effects more common with brofaromine than placebo included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No clinically significant variations in vital signs or laboratory values were found. The findings are consistent with the clinical efficacy for the treatment of social phobia.
Medication appears effective in treating SP over the short term (particularly amongst the SSRIs), and the long term. Nevertheless, the possibility of publication bias has to be acknowledged. Additional issues for future research include the use of medication in children and adolescents with SP, SP with comorbid psychiatric disorders, and performance anxiety.