Anxiety Disorders: Bystritsky A

Bystritsky A. · UCLA, Department of Psychiatry, Los Angeles, CA 90095-6968, USA. · Mol Psychiatry. · Pubmed #16847460 No free full text.

Abstract: Several epidemiological studies confirmed that Anxiety Disorders as a group are the most prevalent psychiatric conditions in the United States. The importance of these conditions is underlined by the fact that they cause significant disability, poor quality of life, alcohol and drug abuse. Anxiety disorders are treatable conditions and respond to the front-line interventions such as serotonin reuptake inhibitors and cognitive behavioral therapy. However, only about 60% of patients respond to those treatments to any significant degree. Many still have residual symptoms or stay treatment refractory. The group of anxiety patients that is resistant to the treatment has been shown to have very poor quality of life and have highest rate of suicidal attempts than any other disorders. Many biological, treatment specific and social factors are affecting treatment resistance. In this paper, we are attempting to review reasons for the treatment resistance. In addition, we would like to review current strategies that could be helpful in reducing treatment resistance and aiding people chronically suffering from these severe and disabling conditions.

Bystritsky A, Kaplan JT, Feusner JD, Kerwin LE, Wadekar M, Burock M, Wu AD, Iacoboni M. · Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095-6968, USA. · J Clin Psychiatry. · Pubmed #18572984 No free full text.

Abstract: BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method that holds promise for treating several psychiatric disorders. Yet the most effective location and parameters for treatment need more exploration. Also, whether rTMS is an effective treatment for individuals with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not been empirically tested. The goal of this pilot study was to evaluate whether functional magnetic resonance imaging (fMRI)-guided rTMS is effective in reducing symptoms of GAD. METHOD: Ten participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program, and between the ages of 18 and 56 years were enrolled in the study from August 2006 to March 2007. A pretreatment symptom provocation fMRI experiment was used to determine the most active location in the prefrontal cortex of the participants. Ten participants completed 6 sessions of rTMS over the course of 3 weeks, stereotactically directed to the previously determined prefrontal location. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement of Illness (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of 1 or 2 ("very much improved" or "much improved," respectively). RESULTS: Overall, rTMS was associated with significant decreases in HAM-A scores (t = 6.044, p = .001) indicative of clinical improvement in GAD symptoms. At endpoint, 6 (60%) of the 10 participants who completed the study showed reductions of 50% or more on the HAM-A and a CGI-I score of 1 or 2; those 6 subjects also had an endpoint HAM-A score < 8, therefore meeting criteria for remission. CONCLUSION: Results of the current study suggest that fMRI-guided rTMS treatment may be a beneficial technique for the treatment of anxiety disorders. Limitations include a small sample size and open-label design with a technology that may be associated with a large placebo response. These limitations necessitate further research to determine whether rTMS is indeed effective in treating anxiety disorders.

Bystritsky A, Kerwin L, Feusner JD. · Department of Psychiatry, University of California, Los Angeles, CA, USA. · J Altern Complement Med. · Pubmed #18307390 No free full text.

Abstract: BACKGROUND: Rhodiola rosea is an herbal supplement that many in the general population in Russia and elsewhere in the world have used for decades to alleviate everyday anxiety, depression, and insomnia. Whether R. rosea is effective in reducing similar symptoms in clinical samples is unknown. The goal of this pilot study was to evaluate whether R. rosea is effective in reducing symptoms of generalized anxiety disorder (GAD). METHOD: Ten (10) participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program and between the ages of 34 and 55, were enrolled in this study from November 2005 to May 2006. Participants received a total daily dose of 340 mg of R. rosea extract for 10 weeks. Assessments included the Hamilton Anxiety Rating Scale (HARS), the Four-Dimensional Anxiety and Depression Scale, and the Clinical Global Impressions of Severity/Improvement Scale. RESULTS: Individuals treated with R. rosea showed significant decreases in mean HARS scores at endpoint (t=3.27, p=0.01). Adverse events were generally mild or moderate in severity, the most common being dizziness and dry mouth. CONCLUSIONS: Significant improvement in GAD symptoms was found with R. rosea, with a reduction in HARS scores similar to that found in clinical trials. These preliminary findings warrant further exploration of treatment with R. rosea in clinical samples.

Roy-Byrne PP, Craske MG, Stein MB, Sullivan G, Bystritsky A, Katon W, Golinelli D, Sherbourne CD. · Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine at Harborview Medical Center, Seattle, USA. · Arch Gen Psychiatry. · Pubmed #15753242 links to  free full text

Abstract: BACKGROUND: Panic disorder is a prevalent, often disabling condition among patients in the primary care setting. Although numerous studies have assessed the effectiveness of treatments for depression in primary care, few such studies have been conducted for panic disorder. OBJECTIVE: To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting. DESIGN: Randomized, controlled study comparing intervention to treatment as usual. SETTING: Six primary care clinics associated with 3 university medical schools, serving an ethnically and socioeconomically diverse patient population. PARTICIPANTS: Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder. Comorbid mental and physical disorders were permitted, provided these did not contraindicate the treatment to be provided and were not acutely life threatening. INTERVENTION: Patients were randomized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions (across 12 weeks) of cognitive-behavioral therapy (CBT) modified for the primary care setting, with up to 6 follow-up telephone contacts during the next 9 months, and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist. Behavioral health specialists, the majority inexperienced in CBT for panic disorder, were trained to deliver the CBT and coordinated overall care, including pharmacotherapy. MAIN OUTCOMES MEASURES: Proportion of subjects remitted (no panic attacks in the past month, minimal anticipatory anxiety, and agoraphobia subscale score <10 on Fear Questionnaire) and responding (Anxiety Sensitivity Index score <20) and change over time in World Health Organization Disability Scale and short form 12 scores. RESULTS: The combined cognitive-behavioral and pharmacotherapeutic intervention resulted in sustained and gradually increasing improvement relative to treatment as usual, with significantly higher rates at all points of both the proportion of subjects remitted (3 months, 20% vs 12%; 12 months, 29% vs 16%) and responding (3 months, 46% vs 27%; 12 months, 63% vs 38%) and significantly greater improvements in World Health Organization Disability Scale (all points) and short form 12 mental health functioning (3 and 6 months) scores. These effects were obtained in spite of similar rates of delivery of guideline-concordant pharmacotherapy to the 2 groups. CONCLUSION: Delivery of evidence-based CBT and medication using the collaborative care model and a CBT-naive, midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder.

Bogan AM, Koran LM, Chuong HW, Vapnik T, Bystritsky A. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. · J Clin Psychiatry. · Pubmed #15669891 No free full text.

Abstract: BACKGROUND: The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment. METHOD: In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score. RESULTS: Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events. CONCLUSION: The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.

Stein MB, Pollack MH, Bystritsky A, Kelsey JE, Mangano RM. · Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0985, USA. · Psychopharmacology (Berl). · Pubmed #15258718 No free full text.

Abstract: RATIONALE: There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition. OBJECTIVE: To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD. METHOD: Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150-225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item (score 1 or 2), and the proportion of remitters (defined as an LSAS score of <or=30). RESULTS: Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150-225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER (at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P<0.001); corresponding remission rates were 31% and 16% (P<0.01). There were no differences in outcome according to venlafaxine ER dosage. CONCLUSIONS: Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade.

Bystritsky A, Ackerman DL, Rosen RM, Vapnik T, Gorbis E, Maidment KM, Saxena S. · Department of Psychiatry and Biobehavioral Sciences, Anxiety Disorders Program, University of California-Los Angeles School of Medicine, Neuropsychiatric Institute and Hospital, 300 UCLA Medical Plaza, Los Angeles, CA 90095, USA. · J Clin Psychiatry. · Pubmed #15119922 No free full text.

Abstract: BACKGROUND: The purpose of this study was to explore the efficacy of adding an atypical antipsychotic, olanzapine, to a serotonin reuptake inhibitor (SRI) in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Twenty-six patients aged between 18 and 65 (mean = 41.2, SD = 11.9) years meeting DSM-IV criteria for OCD, who had not responded to SRIs, were treated for 6 weeks in a double-blind, placebo-controlled augmentation study with either olanzapine (up to 20 mg/day) or placebo. Severity of illness was assessed biweekly by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Analysis of covariance with baseline Y-BOCS score included as a covariate was used to compare improvement in Y-BOCS scores in the 2 groups. Response was defined as a 25% or greater improvement in Y-BOCS score. Data were collected between April 2001 and May 2003. RESULTS: Outcome was assessed for all patients using the last observation carried forward. Subjects in the olanzapine group had a mean decrease of 4.2 (SD = 7.9) in Y-BOCS score compared with a mean increase in score of 0.54 (SD = 1.31) for subjects in the placebo group (F = 4.85, df = 2,23; p =.04). Six (46%) of 13 subjects in the olanzapine group showed a 25% or greater improvement in Y-BOCS score compared with none in the placebo group. The final mean dose of olanzapine was 11.2 (SD = 6.5) mg/day. Medication was well tolerated. Only 2 (15%) of 13 subjects who received olanzapine discontinued because of side effects: sedation (N = 1) or weight gain (N = 1). CONCLUSION: These results provide preliminary evidence that adding olanzapine to SRIs is potentially efficacious and well tolerated in the short-term treatment of patients with refractory OCD. Controlled studies with larger sample sizes are necessary to more definitively address this treatment strategy.

Hazlett-Stevens H, Craske MG, Roy-Byrne PP, Sherbourne CD, Stein MB, Bystritsky A. · University of California, Los Angeles, CA, USA. · Gen Hosp Psychiatry. · Pubmed #12220797 No free full text.

Abstract: The purpose of this investigation was to identify demographic and clinical patient characteristics related to willingness to consider panic disorder treatments in the primary care setting. Given the prevalence of anxiety disorders and the increased provision of mental health treatments in general medical settings, patients were selected from primary care settings. An unselected sample of 4,198 patients completed a brief questionnaire containing questions about demographic characteristics, physical health status, and symptoms of panic disorder, social phobia and PTSD. The 1,043 patients indicating a recent panic attack episode answered additional questions about their willingness to consider both medication and psychosocial forms of intervention for panic. Of these panic patients, 64% reported willingness to consider medication and 67% reported willingness to consider a psychosocial intervention for their panic. Logistic regression analyses for these panic patients revealed that willingness to consider medication treatment for panic was associated with older age, lower education, poorer health status and the presence of social phobia and/or PTSD symptoms. In addition, Asian and African American patients were less likely than Caucasian patients to indicate willingness to consider medication treatment for their panic. However, only the presence of comorbid social phobia and PTSD symptoms predicted willingness to consider a psychosocial intervention. Results suggest that acceptability of psychosocial treatment is unrelated to demographic and physical health factors, while primary care patients with certain demographic characteristics, good physical health, or who suffer from fewer comorbid mental health conditions may need additional encouragement to begin medication treatment for panic.

Saxena S, Winograd A, Dunkin JJ, Maidment K, Rosen R, Vapnik T, Tarlow G, Bystritsky A. · Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, Los Angeles, Calif 90095, USA. · J Clin Psychiatry. · Pubmed #11235937 No free full text.

Abstract: BACKGROUND: Although body dysmorphic disorder (BDD) has many features in common with obsessive-compulsive disorder (OCD) and is frequently comorbid with OCD, few studies have directly compared the 2 disorders. Although BDD and OCD respond to similar medications and cognitive-behavioral therapy (CBT), their response to treatment has never been directly compared. METHOD: We studied 107 consecutive patients with DSM-III-R OCD (N = 96) or BDD (N = 11) treated openly for 6 weeks with intensive CBT, medication, and psychosocial rehabilitation, in a specialized partial hospitalization program for severely ill OCD patients. All patients were assessed, before and after treatment, with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Global Assessment Scale (GAS). Retrospectively, we compared the clinical characteristics, symptom severity, and response to treatment of BDD patients with those of OCD patients. RESULTS: BDD patients and OCD patients had similar sex ratio, age, treatment duration, prevalence of comorbid major depression, and pretreatment Y-BOCS and GAS scores. BDD patients had significantly higher pretreatment HAM-D and HAM-A scores. The proportions of patients treated with serotonin reuptake inhibitors and antipsychotics did not differ between groups. Both groups improved with treatment, with significant (p < .001) changes in Y-BOCS, HAM-D, HAM-A, and GAS scores. Change in Y-BOCS did not differ between groups, but changes in HAM-D and HAM-A were significantly greater in BDD patients than in OCD patients. CONCLUSION: While BDD may be associated with greater severity of depressive and anxiety symptoms than OCD, this study suggests that BDD may respond to intensive, multimodal treatment.

Bystritsky A, Rosen R, Suri R, Vapnik T. · Department of Psychiatry, U.C.L.A. School of Medicine, USA. · Depress Anxiety. · Pubmed #10604088 No free full text.

Abstract: Ten patients meeting DSM-IV criteria for non-comorbid panic disorder or panic disorder with agoraphobia were treated in a 12-week open-label, flexible dosage trial of nefazodone. Dosages ranged from 50 to 400 mg per day. Clinical assessment utilized several recently developed scales of panic disorder severity, as well as the clinical global impression scale. At the conclusion of the study, 9 out of 10 patients were rated much improved with 7 of the patients rated as panic free and in full remission. Significantly improved scores were reflected by all of the scales. Low sample size and absence of placebo control indicate the need for a large placebo-controlled trial. The results of this pilot study suggest that nefazodone may be promising in the treatment of panic and justify further research.

Ackerman DL, Greenland S, Bystritsky A. · Department of Epidemiology, UCLA School of Public Health, Los Angeles, California 90095, USA. · J Clin Psychopharmacol. · Pubmed #10505588 No free full text.

Abstract: Differences between the side effect profiles of clomipramine (CMI) and the selective serotonin reuptake inhibitors may be important factors in both treatment outcome and patient selection in obsessive-compulsive disorder (OCD). Safety and efficacy data from an industry-sponsored, multicenter clinical trial of CMI were analyzed previously using tabular and multiple regression methods. Good response, defined as at least a 35% drop in final scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), was associated with a later age of OCD onset and certain early side effects that may reflect a sensitivity of responders to CMI's serotonergic actions. The authors conducted a similar analysis of data from an industry-sponsored clinical trial of fluoxetine in OCD. Fluoxetine response did not seem to be associated with age of OCD onset. Good response to both drugs was associated with initial nervousness and sexual complaints. The common side effects of fluoxetine (headache, nausea, and gastrointestinal complaints) did not seem to be associated with treatment response. Slight differences in the protocols of the two clinical trials yielded patient populations that were different in factors found to be associated with treatment outcome: subjects in the fluoxetine study had lower scores on the Y-BOCS, higher scores on the Hamilton Rating Scale for Depression, and an earlier age of OCD onset.

Stein MB, Roy-Byrne PP, McQuaid JR, Laffaye C, Russo J, McCahill ME, Katon W, Craske M, Bystritsky A, Sherbourne CD. · Department of Psychiatry, University of California, San Diego, La Jolla 92093-0985, USA. · Psychosom Med. · Pubmed #10367617 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to determine the utility of a brief screening tool for panic disorder in the primary care setting. METHODS: A total of 1476 primary care outpatients in three primary care medical clinics on the West Coast of the United States were studied. Patients completed a brief self-report measure, the five-item Autonomic Nervous System Questionnaire (ANS), while in the waiting room. The presence of DSM-IV panic disorder was subsequently determined in groups of "screen-positive" and "screen-negative" subjects using the Composite International Diagnostic Interview. A subset of patients (N = 511) also completed the 21-item Beck Anxiety Inventory. Indices of diagnostic utility were calculated using receiving operating characteristic analyses to guide the selection of optimal cutoff levels. RESULTS: The two-question version of the ANS had excellent sensitivity (range = 0.94-1.00 across the three clinic sites) and negative predictive value (0.94-1.00) but low specificity (0.25-0.59) and positive predictive value (range 0.18-0.40). The three- and five-question versions of the ANS had only modestly improved specificity, and this was achieved at the cost of reduced sensitivity and increased respondent burden to complete the questionnaire. The 21-item Beck Anxiety Inventory had maximal clinical utility at a cutoff level of > or =20, but sensitivity was lower than desirable for a screening instrument (0.67). CONCLUSIONS: The two-question version of the ANS shows promise as a screening instrument for panic disorder in the primary care setting.

Kronig MH, Apter J, Asnis G, Bystritsky A, Curtis G, Ferguson J, Landbloom R, Munjack D, Riesenberg R, Robinson D, Roy-Byrne P, Phillips K, Du Pont IJ. · Department of Psychiatry, Hillside Hospital of LIJMC, Glen Oaks, New York, USA. · J Clin Psychopharmacol. · Pubmed #10211919 No free full text.

Abstract: The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.

Bystritsky A, Saxena S, Maidment K, Vapnik T, Tarlow G, Rosen R. · University of California, Los Angeles, Neuropsychiatric Institute and Hospital, 90024, USA. · Psychiatr Serv. · Pubmed #10096650 links to  free full text

Abstract: Thirty treatment-resistant patients with a primary DSA-IV diagnosis of obsessive-compulsive disorder were assessed at admission to and discharge from a partial hospitalization program to determine whether improvement in symptoms of the disorder was associated with improvements in patients' quality of life. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Quality of life was measured using Lehman's Quality of Life (QOL) scale, which includes several objective and subjective indexes. YBOCS scores significantly improved with treatment, as did scores on the majority of the QOL subjective indexes and on the objective social, health, and activity indexes. No significant association between changes in YBOCS scores and QOL scores was found.

Feusner JD, Townsend J, Bystritsky A, McKinley M, Moller H, Bookheimer S. · Department of Psychiatry, University of California, Los Angeles, CA 90095, United States. · Psychiatry Res. · Pubmed #19328661 No free full text.

Abstract: Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived defects in their appearance. Little is known of the pathophysiology or neurobiology of BDD. Recent evidence from a functional MRI study examining visual processing of faces demonstrated abnormal activation patterns in regions including left-sided inferior frontal gyrus (IFG) and amygdala. To investigate morphometric abnormalities, we compared brain volumes from high-resolution T1 magnetic resonance images of 12 unmedicated subjects with BDD to images of 12 matched controls using voxel-based morphometry (VBM). In addition, we compared volumes in specific regions of interest including the IFG, amygdala, caudate, and total grey and white matter and examined correlations with symptom severity. VBM revealed no statistically significant volumetric differences, nor were there significant differences in any of the regions of interest. However, there were significant positive correlations between scores on the BDD version of the Yale-Brown Obsessive-Compulsive Disorder Scale (BDD-YBOCS) and volumes of the left IFG (r=0.69) and the right amygdala (r=0.54). These findings of correlations between BDD symptom severity and volumes of the left IFG and the right amygdala. These are in concordance with the involvement of these regions in pathological face processing, which may contribute to the primary symptomatology.

Roy-Byrne P, Veitengruber JP, Bystritsky A, Edlund MJ, Sullivan G, Craske MG, Welch SS, Rose R, Stein MB. · Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Harborview Center for Healthcare Improvement for Addictions, Mental Illness and Medically Vulnerable Populations, Seattle, USA. · J Am Board Fam Med. · Pubmed #19264941 links to  free full text

Abstract: To address the difficulty of assessing and managing multiple anxiety disorders in the primary care setting, this article provides a simple, easy-to-learn, unified approach to the diagnosis, care management, and pharmacotherapy of the 4 most common anxiety disorders found in primary care: panic, generalized anxiety disorders, social anxiety disorders, and posttraumatic stress disorder. This evidence-based approach was developed for an ongoing National Institute of Mental Health-funded study designed to improve the delivery of evidence-based medication and psychotherapy treatment to primary care patients with these anxiety disorders. We present a simple, validated method to screen for the 4 major disorders that emphasizes identifying other medical or psychiatric comorbidities that can complicate treatment; an approach for initial education of the patient and discussion about treatment, including provision of some simple cognitive behavioral therapy skills, based on motivational interviewing/brief intervention approaches previously used for substance use disorders; a validated method for monitoring treatment outcome; and an algorithmic approach for the selection of initial medication treatment, the selection of alternative or adjunctive treatments when the initial approach has not produced optimal results, and indications for mental health referral.

Craske MG, Rose RD, Lang A, Welch SS, Campbell-Sills L, Sullivan G, Sherbourne C, Bystritsky A, Stein MB, Roy-Byrne PP. · Department of Psychology, University of California, Los Angeles, California, USA. · Depress Anxiety. · Pubmed #19212970 No free full text.

Abstract: OBJECTIVES: This article describes a computer-assisted cognitive behavioral therapy (CBT) program designed to support the delivery of evidenced-based CBT for the four most commonly occurring anxiety disorders (panic disorder, posttraumatic stress disorder, generalized anxiety disorder, and social anxiety disorder) in primary-care settings. The purpose of the current report is to (1) present the structure and format of the computer-assisted CBT program, and (2) to present evidence for acceptance of the program by clinicians and the effectiveness of the program for patients. METHODS: Thirteen clinicians using the computer-assisted CBT program with patients in our ongoing Coordinated Anxiety Learning and Management study provided Likert-scale ratings and open-ended responses about the program. Rating scale data from 261 patients who completed at least one CBT session were also collected. RESULTS: Overall, the program was highly rated and modally described as very helpful. Results indicate that the patients fully participated (i.e., attendance and homework compliance), understood the program material, and acquired CBT skills. In addition, significant and substantial improvements occurred to the same degree in randomly audited subsets of each of the four primary anxiety disorders (N=74), in terms of self ratings of anxiety, depression, and expectations for improvement. CONCLUSIONS: Computer-assisted CBT programs provide a practice-based system for disseminating evidence-based mental health treatment in primary-care settings while maintaining treatment fidelity, even in the hands of novice clinicians.

Powers MB, Smits JA, Whitley D, Bystritsky A, Telch MJ. · Faculty of Social and Behavioral Sciences, University of Amsterdam, Amsterdam, the Netherlands. · J Consult Clin Psychol. · Pubmed #18540741 No free full text.

Abstract: In this investigation, the authors examined the effect of attributional processes concerning medication taking on return of fear following exposure-based treatment. Participants (87% undergraduate students and 13% community volunteers) displaying marked claustrophobic fear (N = 95) were randomly allocated to a waitlist condition, a psychological placebo condition, a 1-session exposure-based treatment, or the same exposure treatment given in conjunction with an inactive pill. Attributions concerning medication taking were manipulated by further randomly assigning participants in the exposure-based treatment plus pill condition to 1 of 3 instructional sets immediately following treatment completion and posttreatment assessment: (1) The pill was described as a sedating herb that likely made exposure treatment easier; (2) the pill was described as a stimulating herb that likely made exposure treatment more difficult; or (3) the pill was described as a placebo that had no effect on exposure treatment. Return of fear rates for the 3 conditions were 39%, 0%, and 0%, respectively. Moreover, the deleterious effects of the sedation instructions were mediated by reduced self-efficacy. These findings highlight the importance of assessing patient attributions regarding the improvements achieved with combined exposure-based and pharmacological treatments for anxiety disorders.

Campbell-Sills L, Norman SB, Craske MG, Sullivan G, Lang AJ, Chavira DA, Bystritsky A, Sherbourne C, Roy-Byrne P, Stein MB. · Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0603, USA. · J Affect Disord. · Pubmed #18486238 No free full text.

Abstract: BACKGROUND: The Overall Anxiety Severity and Impairment Scale (OASIS) is a 5-item self-report measure that can be used to assess severity and impairment associated with any anxiety disorder or multiple anxiety disorders. A prior investigation with a nonclinical sample supported the reliability and validity of the OASIS; however, to date it has not been validated for use in clinical samples. METHODS: The present study assessed the psychometric properties of the OASIS in a large sample (N=1036) of primary care patients whose physicians referred them to an anxiety disorders treatment study. Latent structure, internal consistency, convergent/discriminant validity, and cut-score analyses were conducted. RESULTS: Exploratory and confirmatory factor analyses supported a unidimensional structure. The five OASIS items displayed strong loadings on the single factor and had a high degree of internal consistency. OASIS scores demonstrated robust correlations with global and disorder-specific measures of anxiety, and weak correlations with measures of unrelated constructs. A cut-score of 8 correctly classified 87% of this sample as having an anxiety diagnosis or not. LIMITATIONS: Convergent validity measures consisted solely of other self-report measures of anxiety. Future studies should evaluate the convergence of OASIS scores with clinician-rated and behavioral measures of anxiety severity. CONCLUSIONS: Overall, this investigation suggests that the OASIS is a valid instrument for measurement of anxiety severity and impairment in clinical samples. Its brevity and applicability to a wide range of anxiety disorders enhance its utility as a screening and assessment tool.

Bystritsky A, Kerwin L, Feusner J. · Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095-6968, USA. · J Clin Psychiatry. · Pubmed #18348596 No free full text.

Abstract: BACKGROUND: Cranial electrotherapy stimulation (CES) is a noninvasive procedure that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. Whether CES is an effective treatment for patients with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not previously been explored. The goal of this study was to evaluate the efficacy of CES in alleviating anxiety in patients with DSM-IV-diagnosed GAD. METHOD: Twelve patients from 29 to 58 years of age with a DSM-IV diagnosis of GAD were enrolled from August 2005 to March 2006 through the University of California, Los Angeles (UCLA) Anxiety Disorders Program. Cranial electrotherapy stimulation treatment was administered for 6 weeks using the Alpha-Stim Stress Control System at 0.5-Hz frequency and 300-muA intensity. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of 1 or 2 ("much improved" or "very much improved," respectively). RESULTS: Cranial electrotherapy stimulation was associated with a significant decrease in HAM-A scores (t = 3.083, p = .01). At endpoint, 6 patients (50% of the intent-to-treat sample and 67% of completers) had a 50% decrease in HAM-A score and a CGI-I score of 1 or 2. One additional patient significantly improved in anxiety scores but did not meet criteria for response. Adverse events were generally mild in severity, mostly consisting of headache and nausea. CONCLUSION: This preliminary study suggests that CES may reduce symptoms of anxiety in GAD. We hope that these preliminary results will encourage further research to explore the use of CES in clinical settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00539357.

Feusner JD, Townsend J, Bystritsky A, Bookheimer S. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California, Los Angeles, 300 UCLA Medical Plaza, Ste 2345, Los Angeles, CA 90024, USA. · Arch Gen Psychiatry. · Pubmed #18056550 links to  free full text

Abstract: CONTEXT: Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived appearance defects. Clinical observation suggests that patients with BDD focus on details of their appearance at the expense of configural elements. This study examines abnormalities in visual information processing in BDD that may underlie clinical symptoms. OBJECTIVE: To determine whether patients with BDD have abnormal patterns of brain activation when visually processing others' faces with high, low, or normal spatial frequency information. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: Twelve right-handed, medication-free subjects with BDD and 13 control subjects matched by age, sex, and educational achievement. Intervention Functional magnetic resonance imaging while performing matching tasks of face stimuli. Stimuli were neutral-expression photographs of others' faces that were unaltered, altered to include only high spatial frequency visual information, or altered to include only low spatial frequency visual information. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes in the BDD and control groups during tasks with each stimulus type. RESULTS: Subjects with BDD showed greater left hemisphere activity relative to controls, particularly in lateral prefrontal cortex and lateral temporal lobe regions for all face tasks (and dorsal anterior cingulate activity for the low spatial frequency task). Controls recruited left-sided prefrontal and dorsal anterior cingulate activity only for the high spatial frequency task. CONCLUSIONS: Subjects with BDD demonstrate fundamental differences from controls in visually processing others' faces. The predominance of left-sided activity for low spatial frequency and normal faces suggests detail encoding and analysis rather than holistic processing, a pattern evident in controls only for high spatial frequency faces. These abnormalities may be associated with apparent perceptual distortions in patients with BDD. The fact that these findings occurred while subjects viewed others' faces suggests differences in visual processing beyond distortions of their own appearance.

Sullivan G, Craske MG, Sherbourne C, Edlund MJ, Rose RD, Golinelli D, Chavira DA, Bystritsky A, Stein MB, Roy-Byrne PP. · South Central VA Mental Illness Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, North Little Rock, AR 72214-1706, USA. · Gen Hosp Psychiatry. · Pubmed #17888803 links to  free full text

Abstract: BACKGROUND: Despite a marked increase in the number of persons seeking help for anxiety disorders, the care provided may not be evidence based, especially when delivered by nonspecialists. Since anxiety disorders are most often treated in primary care, quality improvement interventions, such as the Coordinated Anxiety Learning and Management (CALM) intervention, are needed in primary care. RESEARCH DESIGN: This study is a randomized controlled trial of a collaborative care effectiveness intervention for anxiety disorders. SUBJECTS: Approximately 1040 adult primary care patients with at least one of four anxiety disorders (generalized anxiety disorder, panic disorder, posttraumatic stress disorder or social anxiety disorder) will be recruited from four national sites. INTERVENTION: Anxiety clinical specialists (ACSs) deliver education and behavioral activation to intervention patients and monitor their symptoms. Intervention patients choose cognitive-behavioral therapy, antianxiety medications or both in "stepped-care" treatment, which varies according to clinical needs. Control patients receive usual care from their primary care clinician. The innovations of CALM include the following: flexibility to treat any one of the four anxiety disorders, co-occurring depression, alcohol abuse or both; use of on-site clinicians to conduct initial assessments; and computer-assisted psychotherapy delivery. EVALUATION: Anxiety symptoms, functioning, satisfaction with care and health care utilization are assessed at 6-month intervals for 18 months. CONCLUSION: CALM was designed for clinical effectiveness and easy dissemination in a variety of primary care settings.

Craske MG, Roy-Byrne P, Stein MB, Sullivan G, Hazlett-Stevens H, Bystritsky A, Sherbourne C. · University of California, Los Angeles, Los Angeles, CA 90095-1563, USA. · Behav Ther. · Pubmed #16942966 No free full text.

Abstract: A hybrid efficacy-effectiveness design in which participants (n = 91/93) were retained in the study regardless of whether or not they received treatment enabled evaluation of CBT intensity in relation to panic disorder in the primary care setting. CBT intensity was operationalized as number of cognitive-behavioral therapy sessions, number of follow-up booster phone calls, and secondarily, as number of cognitive behavioral coping and exposure strategies. Baseline psychosocial and demographic predictors of CBT intensity were analyzed first. Severity of anxiety sensitivity predicted number of cognitive behavioral sessions, but no baseline variables predicted number of follow-up booster phone calls or number of coping and exposure strategies. Multivariate logistic and linear regressions were used to evaluate the degree to which treatment intensity predicted 3-month and 12-month outcomes (anxiety sensitivity, phobic avoidance, depressive symptoms, disability, and medical and mental health functioning) after controlling for potential confounding baseline variables. Number of cognitive behavioral therapy sessions predicted lower anxiety sensitivity at 3 and 12 months, and number of follow-up booster phone calls predicted lower anxiety sensitivity, less phobic avoidance, and less depression at 12 months. These findings indicate that "dose" of psychotherapy was an important predictor of outcome. The significance of follow-up booster phone contact is discussed as an index of continued self-management of panic and anxiety following acute treatment.

Stein MB, Roy-Byrne PP, Craske MG, Bystritsky A, Sullivan G, Pyne JM, Katon W, Sherbourne CD. · Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0985, USA. · Med Care. · Pubmed #16299426 No free full text.

Abstract: OBJECTIVE: The objective of this study was to examine the relative impact of anxiety disorders and major depression on functional status and health-related quality of life of primary care outpatients. METHOD: Four hundred eighty adult outpatients at an index visit to their primary care provider were classified by structured diagnostic interview as having anxiety disorders (panic disorder with or without agoraphobia, social phobia, and posttraumatic stress disorder; generalized anxiety disorder was also assessed in a subset) with or without major depression. Functional status, sick days from work, and health-related quality of life (including a preference-based measure) were assessed using standardized measures adjusting for the impact of comorbid medical illnesses. Relative impact of the various anxiety disorders and major depression on these indices was evaluated. RESULTS: In multivariate regression analyses simultaneously adjusting for age, sex, number of chronic medical conditions, education, and/or poverty status, each of major depression, panic disorder, posttraumatic stress disorder, and social phobia contributed independently and relatively equally to the prediction of disability and functional outcomes. Generalized anxiety disorder had relatively little impact on these indices when the effects of comorbid major depression were considered. Overall, anxiety disorders were associated with substantial decrements in preference-based health states. CONCLUSIONS: These observations demonstrate that the presence of each of 3 common anxiety disorders (ie, panic disorder, posttraumatic stress disorder, and social phobia)-over and above the impact of chronic physical illness, major depression, and other socioeconomic factors-contributes in an approximately additive fashion to the prediction of poor functioning, reduced health-related quality of life, and more sick days from work. Greater awareness of the deleterious impact of anxiety disorders in primary care is warranted.

Craske MG, Golinelli D, Stein MB, Roy-Byrne P, Bystritsky A, Sherbourne C. · Department of Psychology, University of California-Los Angeles, 405 Holgard Avenue, Los Angeles, CA 90095, USA. · Psychol Med. · Pubmed #16219122 No free full text.

Abstract: BACKGROUND: Randomized clinical trials indicate a benefit from combining medications with cognitive behavioral therapy (CBT) relative to medication alone for panic disorder. Using an as-treated analysis, we evaluated whether the addition of CBT enhanced outcomes for panic disorder relative to medications alone in the primary-care setting. METHOD: Primary-care patients with panic disorder reported on their receipt of CBT and medications over the 3 months following baseline assessment. The degree to which outcomes for those who used anti-panic medications were enhanced by the receipt of at least one component of CBT was analyzed using a propensity score model that took into account observable baseline patient characteristics influencing both treatment selection and outcomes. RESULTS: The addition of CBT resulted in statistically and clinically significant improvements at 3 months on anxiety sensitivity, social avoidance, and disability. Also, patients receiving CBT in the first 3 months of the study were more improved at 12 months than patients who took medications only during the first 3 months of the study. CONCLUSIONS: The clinical utility of the findings are discussed in terms of the importance of primary-care physicians encouraging their panic disorder patients to receive CBT as well as medications.