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Biomedical subjects

A Bystritsky

Publications and source records attributed to A Bystritsky.

At least 19 recordsLinked to original sources

Treatment-resistant anxiety disorders.

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.

Anxiety Disorders↗

Functional MRI changes during panic anticipation and imagery exposure.

While undergoing fMRI, six patients with DSM IV diagnosis of panic disorder and six normal controls performed directed imagery of neutral, moderate and high anxiety situations based on an individually determined behavioral hierarchy. Brain activity was compared during high vs neutral anxiety blocks for each group of subjects using SPM99b. Panic patients showed increased activity in inferior frontal cortex, hippocampus and throughout the cingulate both anterior and posterior, extending into the orbitofrontal cortex and encompassing both hemispheres. These areas may constitute the important circuit in the psychopathology of panic disorder. We propose that this pattern of activity may enhance the encoding and retrieval of strong emotional events, facilitating the recapitulation of traumatic experiences and leading to panic disorder in vulnerable individuals.

Adult↗

Social functioning and quality of life comparisons between obsessive-compulsive and schizophrenic disorders.

Treatment of obsessive-compulsive disorder has focused almost exclusively on symptom reduction; however, deficits in social functioning and quality of life of individuals with this disorder may contribute more to their "burden," suffering, and disability. To gauge the significance of social dysfunction and quality of life of persons with obsessive-compulsive disorder (OCD), we made comparisons with a group of persons with schizophrenia matched for age and gender. Thirty-one patients with OCD participating in a partial hospital treatment program were compared with 68 schizophrenic outpatients participating in a day rehabilitation program. The Independent Living Skills Survey (ILSS) and Lehman Quality of Life Scale (QOL) were administered before and after treatment for both cohorts. QOL scores were significantly lower for the OCD patients both before and after treatment, but improved significantly during treatment. OCD and schizophrenic patients had similar scores on almost every domain of the ILSS at pretreatment. The OCD patients improved significantly on many of the domains of social and independent living skills as a result of treatment and acquired significantly greater skills by post-treatment than did their counterparts with schizophrenia; however, the performance of social and independent living skills by OCD patients remained less than satisfactory even in domains where they improved. In the areas of job and leisure skills, there were significant group-by-time interactions. We concluded that patients with severe OCD and patients with schizophrenia are equally socially impaired. However, OCD patients experience greater significant functional improvement with multimodal treatment.

Activities of Daily Living↗

A retrospective review of clinical characteristics and treatment response in body dysmorphic disorder versus obsessive-compulsive disorder.

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.

Adult↗

Autonomic reactivity of panic patients during a CO2 inhalation procedure.

The objectives of this study were to compare continuous subjective and physiological responses of panic disorder patients and normal controls during 5% CO2 inhalation. Psychophysiological responses of panic disorder patients (n = 42) and controls (n = 25) were monitored during baseline (20 min), 5% CO2 inhalation (20 min), and recovery (20 min). The data were compared at baseline and over periods of the experiment using analysis of variance. A subgroup of patients who experienced panic attacks during the CO2 inhalation (n = 12) were significantly different from the other subjects on baseline heart rate and on variability of systolic and diastolic blood pressure, skin conductance, and breathing variability (length and number of breathing pauses and length of breathing cycle variability). Inspection of the data showed that elevation in blood pressure and breathholding were present during some of the panic attacks, suggesting that some attacks may represent a complex psychophysiological response with elements of a "freezing" reaction, well described in animal experiments, which can quickly shift to a "fight/flight" reaction that is usually characterized by an increase in heart and breathing rate. However, some patients had only minimal changes in breathing and others had minimal psychophysiological changes during the time they indicated that they had a panic attack. Panic attacks are not homogeneous and may be characterized by a variety of physiological and cognitive responses. This may indicate that biological mechanisms of panic include abnormality in many functionally connected areas of the brain responsible for complex psychophysiological reactions to multiple threatening situations.

Administration, Inhalation↗

Side effects and time course of response in a placebo-controlled trial of fluoxetine for the treatment of geriatric depression.

A high rate of improvement among patients who receive placebo in controlled trials of antidepressants can complicate the evaluation of true drug effect. Placebo response may be a reaction to the psychosocial factors of study participation or a function of changes in the natural course of depression. Drug side effects may also influence patients' expectations, and they should be distinguished from the somatic symptoms associated with major depression. The authors reanalyzed data from a large, multicenter, placebo-controlled clinical trial of fluoxetine treatment of geriatric depression to evaluate similarities and differences between responders and nonresponders in both treatment groups. Specifically, the authors examined weekly somatic complaints as possible predictors of response and of dropout, as well as the time course and onset of response. Fluoxetine was superior to placebo on all outcome measures. Among somatic complaints associated with fluoxetine response, headache before and after randomization was associated with a good response and anxiety after randomization was associated with a poor response. Somnolence before and after randomization was associated with a good placebo response. Early and persistent improvement occurred among similar proportions of responders in both groups. The difference between fluoxetine and placebo seemed to be a persistent response beginning during the 4th week. Pretreatment somnolence was associated with early, persistent improvement in both groups and may serve as a marker for placebo response.

Aged↗

Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

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.

Adult↗

Side effects as predictors of drug response in obsessive-compulsive disorder.

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.

Adolescent↗

Quality-of-life changes among patients with obsessive-compulsive disorder in a partial hospitalization program.

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.

Adult↗

Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment.

BACKGROUND: Increased medical service utilization in patients with panic disorder has been described in epidemiologic studies, although service use in primary care panic patients relative to other primary care patients is less well characterized. Inadequate recognition of panic has been shown in several primary care studies, although the nature of usual care for panic in this setting has not been well documented. This study aimed to document increased service use in panic patients relative to other primary care patients and to characterize the nature of their usual care for panic and their outcome. METHOD: Using a waiting room screening questionnaire and follow-up telephone interview with the Composite International Diagnostic Interview, we identified a convenience sample of 81 patients with panic disorder (DSM-IV) and a control group of 183 psychiatrically healthy patients in 3 primary care settings on the West Coast and determined psychiatric diagnostic comorbidity, panic characteristics, disability, and medical and mental health service use, including medications. A subsample (N = 41) of panic patients was reinterviewed 4-10 months later to determine the persistence of panic and the adequacy of intervening treatment received using the Harvard/Brown Anxiety Disorders Research Program study criteria for cognitive-behavioral therapy (CBT) and an algorithm developed by the authors for medications. RESULTS: Seventy percent of panic patients had a comorbid psychiatric diagnosis. Patients had more disability in the last month (days missed or cut down activities) (p < .01), more utilization of emergency room and medical provider visits (p < .01), and more mental health visits (p < .05). Despite the latter, only 42% received psychotropic medication, 36% psychotherapy, and 64% any treatment. On follow-up, 85% still met diagnostic criteria for panic, and only 22% had received adequate medication (type and/or dose) and 12% adequate (i.e., CBT) psychotherapy. CONCLUSION: These findings suggest a need for improved treatment interventions for panic disorder in the primary care setting to decrease disability and potentially inappropriate medical service utilization.

Adult↗

Pilot open-label study of nefazodone in panic disorder.

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.

Adult↗

Clinical characteristics of response to fluoxetine treatment of obsessive-compulsive disorder.

Fluoxetine is effective in treating obsessive-compulsive disorder (OCD). Nonetheless, a substantial number of patients do not respond or have only partial improvement. Data generated by a multicenter, placebo-controlled, fixed-dose trial of fluoxetine were reanalyzed to identify characteristics of responders. Multiple regression methods were used to evaluate the relationship between therapeutic response and baseline measures such as severity of symptoms, type of symptoms (obsessions, compulsions, depression), course of illness, previous treatment, age of onset, and other demographic factors (age, race, and sex). Fluoxetine was more effective than placebo on all outcome measures. A 60-mg dosage was associated with a greater drop in Yale-Brown Obsessive-Compulsive Scale total score and a greater drop in Compulsion items than a 20-mg dosage. Response rates and overall improvement were greatest for patients with a history of remissions, with no previous drug treatment or with only prior behavior therapy, with more severe OCD (especially with greater interference and distress from obsessions), or with either low or high Hamilton Rating Scale for Depression scores. This study did not detect any associations between response and current age, age of OCD onset, gender, and race. None of the demographic or clinical factors evaluated was found to be related to improvement in the placebo group.

Adult↗

Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine Collaborative Study Group.

The estrogen decrease of the postmenopausal state may be a factor in both the pathogenesis of late-life depression and in therapeutic response. Studies of nondepressed women over 60 given estrogen replacement therapy (ERT) suggest improvement in mood. The authors compared clinical response of elderly depressed women outpatients entering a 6-week, randomized, placebo-controlled, double-blind, multicenter trial of fluoxetine (20 mg/day); 72 patients received ERT, and 286 did not. There was a significant interaction between ERT status and treatment effect (P = 0.015). Patients on ERT who received fluoxetine had substantially greater mean Ham-D percentage improvement than patients on ERT who received placebo (40.1% vs. 17.0%, respectively); fluoxetine-treated patients not on ERT did not show benefit significantly greater than placebo-treated patients not on ERT. ERT use may augment fluoxetine response in elderly depressed outpatients and should be considered as a factor in clinical trials in elderly women.

Affect↗

Double-blind, placebo-controlled trial of two doses of abecarnil for geriatric anxiety.

We studied the tolerability and efficacy of abecarnil, a new partial benzodiazepine agonist, for short-term relief of anxiety in geriatric patients. After a 1-week placebo lead-in, 182 outpatients (mean +/- SD age = 68.3 +/- 5.8; range, 59-85 years) were randomly assigned in a double-blind, parallel-group design to high-dosage abecarnil (7.5-17.5 mg daily), low-dosage abecarnil (3.0-7.0 mg daily), or placebo for 6 weeks of acute treatment followed by abrupt discontinuation and a 2-week follow-up. During the acute treatment period, the discontinuation rate from adverse events was greater for the group treated with high-dosage abecarnil (44%) than for the groups treated with low-dosage abecarnil (14%) or placebo (12%). The most frequently reported side effects associated with abecarnil were drowsiness and insomnia. For the acute treatment period, low-dosage abecarnil was superior to placebo in reducing anxiety at Weeks 2-4 and 6, and was statistically significantly superior to high-dosage abecarnil at Weeks 4-6. More than half of the placebo group showed at least moderate global improvement at Weeks 3 and 6. One week after abrupt discontinuation of abecarnil, the placebo-treated group had less anxiety than did both groups treated with high-dosage and low-dosage abecarnil. The most commonly reported symptoms of withdrawal were headache and insomnia. These data indicate that abecarnil, at dosages ranging from 3.0 to 7.0 mg daily, is better tolerated and more efficacious for the short-term treatment of anxiety in geriatric patients than are higher dosages of 7.5 to 17.5 mg daily. Abrupt discontinuation of abecarnil at either dosage range causes definite rebound symptoms within the first week after withdrawal. These data also suggest that treatment with placebo offers at least moderate relief of anxiety in many elderly patients.

Age Factors↗