A preliminary investigation of the effects of cognitive behavioral therapy for panic disorder on gastrointestinal distress in patients with comorbid panic disorder and irritable bowel syndrome.

BACKGROUND: High comorbidity between panic disorder with/without agoraphobia (PD/A) and irritable bowel syndrome (IBS) has been identified in the literature. These findings have resulted in the recent development of neurobiological models to explain their overlapping symptoms and related origins. This study was a preliminary investigation of the influence of cognitive behavioral therapy (CBT) for PD/A on PD/A patients with and without comorbid IBS. METHODS: All patients completed a thorough intake assessment, brief waitlist period, and a 12-week CBT group for PD/A. RESULTS: The results demonstrated significant reductions in the symptoms of anxiety, depression, and overall impairment in both patient groups (ts>2.3; Ps<.05). In addition, PD/A patients with comorbid IBS also experienced reductions in the disability and distress associated with their gastrointestinal symptoms of IBS (ts>1.9; Ps<.07). CONCLUSIONS: Although additional research still is needed, these preliminary findings suggest that CBT for PD/A can be used to simultaneously treat comorbid symptoms of PD/A and IBS. Implications for the neurobiological models for these comorbid conditions were discussed.

Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder.

Prior research suggests that SSRIs may have greater efficacy for psychic compared to somatic anxiety, while benzodiazepines show greater somatic efficacy. The goal of this analysis was to evaluate the efficacy of pregabalin (PGB) in treating psychic and somatic symptoms of anxiety. Data were combined from six short-term, double-blind, placebo-controlled, fixed-dose trials of PGB in patients with generalized anxiety disorder (GAD). The following PGB daily dose groups were studied: 150 mg (n=210), 300-450 mg (n=455), and 600 mg (n=406), benzodiazepines (6 mg/d lorazepam and 1.5 mg/d alprazolam, n=299), vs. placebo (n=484). Changes in Hamilton Anxiety Rating Scale (HAMA) psychic and somatic anxiety factors and individual items were analysed. Treatment with 300-600 mg PGB significantly improved both the HAMA psychic and somatic anxiety factors. In contrast, treatment with 150 mg PGB appeared to be less effective, achieving significance only on the psychic anxiety factor. PGB (300-450 mg) was associated with significant improvement on 13 out of 14 HAMA items, while treatment with 600 mg PGB was associated with significant improvement in 10 out of 14 HAMA items. Treatment with benzodiazepines was also associated with significant improvement in both psychic and somatic anxiety factors, with significant improvement occurring in 5 out of 14 HAMA items. The results of this pooled analysis indicate that both PGB and benzodiazepines had significant efficacy in treating both HAMA psychic and somatic anxiety. A dose-response effect was evident for PGB that reached a plateau at a dose of 300 mg/d.

Levetiracetam in generalized social anxiety disorder: a double-blind, randomized controlled trial.

OBJECTIVE: This multicenter, double-blind, placebo-controlled, 2-arm, parallel-group study was carried out to determine the effectiveness and safety of the novel anticonvulsant levetiracetam for the treatment of generalized social anxiety disorder (GSAD). METHOD: After a 1-week, single-blind, placebo run-in period, 217 adult outpatients meeting DSM-IV criteria for social anxiety disorder, generalized type, were randomly assigned (1:1) to 12 weeks of double-blind treatment with either levetiracetam (n = 111) or placebo (n = 106). Participants were required to have scores of >or= 60 on the Liebowitz Social Anxiety Scale (LSAS) and a total score of or= 30% reduction in LSAS score) were similar with 41.3% (levetiracetam) and 46.6% (placebo). No significant between-group differences were found on secondary outcome measures, which included changes in Sheehan Disability Scale, Clinical Global Impression of Change, and HDRS scores. CONCLUSIONS: Although well-tolerated, levetiracetam failed to separate from placebo in this trial for the treatment of moderate to severe GSAD.

Quetiapine monotherapy as treatment for anxiety symptoms in patients with bipolar depression: a pooled analysis of results from 2 double-blind, randomized, placebo-controlled studies.

OBJECTIVE: To evaluate the efficacy and tolerability of quetiapine monotherapy for anxiety symptoms in patients with bipolar disorder experiencing depression in the BipOLar DEpRession (BOLDER I and II) studies. METHOD: A post hoc analysis of anxiety symptoms in 1,051 acutely depressed patients with bipolar I or II disorder (DSM-IV) from 2 double-blind, randomized, placebo-controlled 8-week studies of quetiapine (300 or 600 mg once daily) was conducted. Anxiety symptoms were assessed using Hamilton Anxiety Rating Scale (HARS) total and psychic (items 1-6, 14) and somatic (items 7-13) anxiety subscale scores (mixed-model repeated measure and last-observation-carried-forward analysis of change from baseline at each assessment). The BOLDER I study was conducted between September 2002 and October 2003, and the BOLDER II study was conducted between June 2004 and August 2005. RESULTS: Mean baseline HARS total scores were similar across the treatment groups (300 mg/d: 18.9, 600 mg/d and placebo: both 18.6). There was a significantly greater improvement from baseline in mean HARS total scores at the first evaluation (week 1) in both quetiapine groups compared with placebo (300 mg/d: -4.6, P < .001 and 600 mg/d: -4.1, P = .003 vs placebo: -2.8). These improvements were sustained through week 8 with both quetiapine doses (300 mg/d: -10.1, P < .001 and 600 mg/d: -10.5, P < .001 vs placebo: -6.9). At week 8, there was also significant improvement from baseline in HARS psychic and somatic anxiety subscale scores compared with placebo (P < .001). The baseline severity of anxiety did not impact the improvement in depressive symptoms. Common adverse events included dry mouth, sedation, somnolence, and dizziness. CONCLUSIONS: In this pooled analysis, quetiapine monotherapy was more effective than placebo and generally well tolerated for the treatment of both depressive and anxiety symptoms in patients with bipolar disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00060489 (BOLDER I) and NCT00083954 (BOLDER II).

Low doses of controlled-release paroxetine in the treatment of late-life depression: a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of low daily doses of controlled-release (CR) paroxetine in patients with late-life depression. METHOD: This was a 10-week, multicenter, placebo-controlled, double-blind, fixed-dose trial randomly assigning patients >or= 60 years old to daily doses of paroxetine CR 12.5 mg (N = 168), paroxetine CR 25 mg (N = 177), or placebo (N = 180). Patients had major depressive disorder (DSM-IV criteria) and 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of >or= 18. The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores. The study was conducted from June 2003 to October 2004. RESULTS: The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 (95% CI = -3.41 to -0.19, p = .029) for paroxetine CR 12.5 mg, and -3.3 (95% CI = -4.84 to -1.68, p < .001) for paroxetine CR 25 mg. A significantly larger percentage of patients achieved remission (HAM-D total score or= 60 years of age, although effect sizes are relatively smaller with the 12.5 mg/day dose.

Anxiety disorders and comorbid medical illness.

OBJECTIVE: To provide an overview of the role of anxiety disorders in medical illness. METHOD: The Anxiety Disorders Association of America held a multidisciplinary conference from which conference leaders and speakers reviewed presentations and discussions, considered literature on prevalence, comorbidity, etiology and treatment, and made recommendations for research. Irritable bowel syndrome (IBS), asthma, cardiovascular disease (CVD), cancer and chronic pain were reviewed. RESULTS: A substantial literature supports clinically important associations between psychiatric illness and chronic medical conditions. Most research focuses on depression, finding that depression can adversely affect self-care and increase the risk of incident medical illness, complications and mortality. Anxiety disorders are less well studied, but robust epidemiological and clinical evidence shows that anxiety disorders play an equally important role. Biological theories of the interactions between anxiety and IBS, CVD and chronic pain are presented. Available data suggest that anxiety disorders in medically ill patients should not be ignored and could be considered conjointly with depression when developing strategies for screening and intervention, particularly in primary care. CONCLUSIONS: Emerging data offer a strong argument for the role of anxiety in medical illness and suggest that anxiety disorders rival depression in terms of risk, comorbidity and outcome. Research programs designed to advance our understanding of the impact of anxiety disorders on medical illness are needed to develop evidence-based approaches to improving patient care.

Posttraumatic stress disorder: characteristics and treatment.

This Distance Rounds reviews the DSM-IV definition of posttraumatic stress disorder (PTSD) and associated features. PTSD is a prevalent mental health problem that occurs in some people after combat or civilian trauma and is influenced by certain risk factors. Psychotherapy and pharmacotherapy have both been found efficacious, and treatment selection should be tailored to the individual patient. Pharmacotherapy options include selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, atypical antipsychotics, mood stabilizers, and medications for trauma-related nightmares. Treatment often involves multiple modalities.

Recognition and treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is prevalent, chronic, and potentially disabling. It is characterized by recurrent, unwanted, and distressing thoughts (obsessions) and repetitive, irresistible, behaviors (compulsions). Individuals with OCD recognize that the obsessions and compulsions are senseless or excessive yet they are unable to stop these behaviors. Some etiologic theories of OCD suggest a biological origin, including hypotheses involving the serotonergic system, the glutamatergic system, the orbital cortex and the basal ganglia, and streptococcal throat infections in children. Standard treatments for OCD include selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavior therapy. Combining SSRIs with other medications has relatively little empirical support; however, the adjunctive use of antipsychotics has been shown to be effective. Neurosurgery, such as deep brain stimulation, has also been shown to be effective in select patients with debilitating and refractory OCD.

Recognition and treatment of panic disorder.

Panic disorder is a common, disabling condition that affects 3% to 5% of the world's population. Although it is treatable, panic disorder goes unrecognized and untreated in many patients. Patients with panic disorder have an increased risk for other psychiatric disorders, especially other anxiety disorders, and panic disorder is associated with other medical conditions such as migraines, fibromyalgia, and irritable bowel syndrome. Clinicians treating panic disorder must be able to recognize the disorder, differentiate it from other disorders in which panic attacks are part of the symptomatology, and map out an individualized treatment plan for each patient. This presentation discusses the importance of collaboration between doctor and patient and details available treatment options, including antidepressants, benzodiazepines, and cognitive-behavioral therapy.

Management of treatment-resistant panic disorder.

Panic disorder (PD) is a severe, chronic disorder characterized by one or more unexpected panic attacks followed by worry about additional attacks and/or the implications of the attacks. If attacks are sufficiently severe or frequent, they can promote marked, sometimes debilitating behavioral changes. Many panic disorder sufferers appear to be incompletely responsive to treatment and are subject to relapse after remission. In this article, we highlight the current understanding of the pathophysiology of PD using a "fear circuit" model. Using this model as a reference point, we review the evidence base supporting existing and emerging treatments and suggest strategies for optimizing initial treatment response. Finally, a differential diagnostic approach for clinical evaluation of unsatisfactory response to treatment in PD is presented.

Pharmacological and pharmacokinetic aspects of functional gastrointestinal disorders.

Medications are commonly used for the treatment of patients with functional gastrointestinal disorders. The general goal of this report is to review the pharmacokinetics and pharmacology of medications used in functional gastrointestinal disorders. Methods included literature review, consensus evaluation of the evidence for each topic assigned originally to 1 or 2 authors, and broader review at a harmonization session as part of the Rome III process. This report reviews the animal models that have been validated for the study of effects of pharmacologic agents on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of novel therapeutic agents; the biomarkers validated for studies of sensation and motility end points with experimental medications in humans; the pharmacogenomics applied to these medications and disorders; and the pharmacology of agents that are applied or have potential for treatment of functional gastrointestinal disorders, including psychopharmacologic agents. Clinician and basic investigators involved in the treatment or investigation of functional gastrointestinal disorders or disease models need to have a comprehensive understanding of a vast range of medications. It is anticipated that the interaction between investigators of basic science, basic and applied pharmacology, and clinical trials will lead to better treatment of these disorders.

A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.

OBJECTIVE: Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested against an SNRI in only 1 previous study, and never at an optimal dose. The objective of the current multisite study was to compare relatively higher doses of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225 mg/day) in outpatients with major depressive disorder. METHOD: Subjects with DSM-IV major depressive disorder were randomly assigned to 8 weeks of double-blind treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from January 2002 through January 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression. RESULTS: Both treatments led to significant improvement in depressive symptoms and quality-of-life measures. No significant differences were noted between treatment groups for final scores on the primary or secondary measures. The treatment groups did not differ significantly in the percentage of responders (sertraline = 55%, venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertra-line = 38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor (SSRI) vs. venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and maintained it for 3 weeks, response rates were similar to those found at lower doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR = 50%). CONCLUSIONS: The efficacies of sertraline and venlafaxine XR were comparable. Although response and remission rates did not differ statistically, the rates were analogous to those reported in previous meta-analyses. However, at clinically relevant higher doses, the remission rates were very similar. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00179283.

Efficacy and tolerability of modified-release indiplon in elderly patients with chronic insomnia: results of a 2-week double-blind, placebo-controlled trial.

STUDY OBJECTIVE: Indiplon is a nonbenzodiazepine GABA potentiator, which exhibits pharmacologic selectivity for GABA(A) receptors containing the alpha1 subunit. The aim of the present study was to evaluate the efficacy and safety of a 15-mg nightly dose of modified-release indiplon tablets in elderly patients with primary insomnia characterized by sleep-maintenance difficulties. METHODS: Two hundred twenty-nine elderly patients, aged 65 to 85 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for primary insomnia were randomly assigned to 2 weeks of nightly treatment with either indiplon, 15 mg, or placebo in a double-blind, parallel-group design. Daily sleep diaries were completed to collect patient reports of subjective total sleep time, wake time after sleep onset, number of awakenings after sleep-onset, latency to sleep onset, and sleep quality. Patient global impression ratings of various parameters of sleep were assessed on a weekly basis. RESULTS: The least square mean total sleep time was significantly improved with indiplon versus placebo at week 1 (377 +/- 4 min vs. 328 +/- 4 min; p < .0001) and week 2 (373 +/- 5 min vs. 337 +/- 5 min; p < .0001). Indiplon also significantly improved subjective wake after sleep onset, subjective number of awakenings after sleep onset, subjective sleep-onset latency, sleep quality, and patient global impression ratings of sleep at both weeks 1 and 2. The number and severity of adverse events and rates of discontinuation due to adverse effects were comparable in the indiplon and placebo groups. CONCLUSIONS: In elderly patients with primary insomnia characterized by sleep-maintenance difficulty, indiplon, 15 mg, was well tolerated and significantly improved all patient-reported measures of sleep during 2 weeks of treatment.

Increased prevalence of functional gastrointestinal disorders in panic disorder: clinical and theoretical implications.

BACKGROUND: Functional gastrointestinal disorders (FGID) are a group of disorders characterized by recurrent gastrointestinal distress for which no structural or biochemical cause can be discerned. Irritable bowel syndrome (IBS) is an FGID estimated to affect 10% to 25% of the United States population. IBS occurs in over 40% of individuals with panic disorder, and in patients with IBS, 25% to 30% have panic disorder, which has led to speculation about possible shared pathophysiology between the two. Less is known about the prevalence of other FGID in individuals with panic disorder. OBJECTIVE: The purpose of this study was to examine the prevalence of IBS and all the other FGID in patients with current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) panic disorder. INTRODUCTION: We assessed FGIDs in 73 treatment-seeking DSM-IV panic disorder patients via the Diagnostic Interview Questions for Functional Gastrointestinal Disorders and made descriptive comparisons with a large convenience sample from an already-completed United States Household Survey (USHS), which employed the same diagnostic criteria. RESULTS: The prevalence of IBS and other FGIDs in both men and women with panic disorder were substantially higher than in the USHS respondents. Women with panic disorder had significantly more functional chest pain than men, but there was no gender difference in IBS. With the exception of functional anorectal and biliary disorders, the FGID prevalences were comparatively higher in panic disorder versus the USHS respondents. DISCUSSION: This survey supports earlier reports of a high prevalence of IBS in individuals with panic disorder and also suggests that the prevalence of several other FGIDs were comparatively high as well. Methodological limitations precluded direct statistical analysis. It may be that commonly overlapping psychiatric and often-painful FGIDs, and extra-intestinal disorders increase the risk for comorbidity in already-affected individuals via shared pathophysiology. One potential model for which there is some evidence for a role in stress, panic disorder, FGIDs and several extra-intestinal functional conditions is dysregulation of corticotropin-releasing factor function. CONCLUSION: The prevalence of FGIDs in DSM-IV panic disorder was comparatively higher than in USHS respondent community sample, which used similar FGID diagnostic criteria. The cause for the apparent close association of panic disorder with FGID may represent shared pathophysiology. Increased understanding of the mechanism of the overlap may allow for improved treatment of the significant proportion of the population suffering from comorbid psychiatric and functional medical conditions.

Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam.

BACKGROUND: Pregabalin inhibits release of excess excitatory neurotransmitters, presumably by binding to the alpha2-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord. OBJECTIVE: To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder. DESIGN: Double-blind, placebo-controlled, active-comparator trial. Patients were randomized to 4 weeks of treatment with pregabalin, 300 mg/d (n = 91), 450 mg/d (n = 90), or 600 mg/d (n = 89); alprazolam, 1.5 mg/d (n = 93); or placebo (n = 91). SETTING: Psychiatry research and clinic settings. PATIENTS: Outpatients meeting the DSM-IV criteria for generalized anxiety disorder, with a baseline Hamilton Anxiety Rating Scale (HAM-A) total score of 20 or greater. MAIN OUTCOME MEASURES: Change from baseline to end point in total HAM-A score in the pregabalin and alprazolam groups compared with the placebo group. The end point response criterion was 50% or greater reduction in the HAM-A total score. RESULTS: Pregabalin and alprazolam produced a significantly greater reduction in mean +/- SE HAM-A total score at last-observation-carried-forward end point compared with placebo (-8.4 +/- 0.8): pregabalin, 300 mg (-12.2 +/- 0.8, P<.001), 450 mg (-11.0 +/- 0.8, P = .02), and 600 mg (-11.8 +/- 0.8, P = .002), and alprazolam (-10.9 +/- 0.8, P = .02). By week 1 and at last-observation-carried-forward end point, the 3 pregabalin groups and the alprazolam group had significantly (P<.01) improved HAM-A psychic anxiety symptoms compared with the placebo group. Compared with the placebo group, HAM-A somatic anxiety symptoms were also significantly (P<.02) improved by the 300- and 600-mg pregabalin groups, but not by the 450-mg pregabalin (week 1, P = .06; week 4, P = .32) and the alprazolam groups (week 1, P = .21; week 4, P = .15). Of the 5 treatment groups, the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group. CONCLUSION: Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients.

Neural correlates of speech anticipatory anxiety in generalized social phobia.

Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole)--regions important in automatic emotional processing--and less cortical activity (dorsal anterior cingulate/prefrontal cortex)--regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa.

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication.

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Impact of gastrointestinal symptom severity on response to venlafaxine extended-release in patients with generalized anxiety disorder.

BACKGROUND: This retrospective analysis evaluated the prevalence and severity of pre-treatment gastrointestinal (GI) symptoms in patients with generalized anxiety disorder (GAD), the impact of these GI symptoms on the efficacy and tolerability of venlafaxine extended-release (XR), and the effect of treatment on prestudy GI symptoms. METHOD: Data from 1932 nondepressed GAD patients were pooled from 5 randomized, double-blind, placebo-controlled studies of venlafaxine XR clinically conducted between May 1995 and December 1997. The GI symptom severity at baseline was estimated from item 11 on the Hamilton Rating Scale for Anxiety (HAM-A). Patients with a GI symptom severity score < or = 2 (moderate or less) and those with a GI symptom severity score > 2 (severe/very severe) were compared for baseline characteristics and short-term (8-week) and long-term (24-week) outcomes. RESULTS: At baseline, for all randomized patients with a HAM-A item 11 score, GI symptoms were rated moderate or lower in 82.8% of patients (GI-low) and severe/very severe in 17.2% (GI-high). The GI-high subgroup was statistically significantly (p < .05) younger, had a longer duration of GAD, and had higher mean HAM-A total scores than the GI-low subgroup. Compared with placebo, venlafaxine XR significantly reduced HAM-A total and psychic anxiety factor scores, regardless of baseline GI symptom severity. The incidence of adverse events, particularly nausea, was higher for the GI-high versus GI-low subgroup. CONCLUSION: Baseline severity of GI symptoms correlated with overall severity of GAD but had no impact on treatment outcome with venlafaxine XR. These data do not support the hypothesis that high baseline GI symptom severity has a negative effect on treatment with venlafaxine XR in GAD patients.

Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.

Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d. pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P < or = 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.