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Biomedical subjects

A Bystritsky

Publications and source records attributed to A Bystritsky.

At least 37 records · Page 2Linked to original sources

Characteristics of fluoxetine versus placebo responders in a randomized trial of geriatric depression.

Results from placebo-controlled trials of antidepressants can be used to identify patients most likely to benefit from medication. Using data from a randomized clinical trial of fluoxetine versus placebo for 671 elderly outpatients with major depression, we evaluated characteristics of those who improved with and without active medication. We found that the choice of outcome measure made a difference when evaluating the effectiveness of fluoxetine relative to placebo and determining the accuracy of predictive variables in both treatment groups. Generally, less severe depression predicted favorable response (greater than 50% improvement on the 21-item Hamilton Rating Scale for Depression [HAM-D-21], less than 3 on the Clinical Global Impressions [CGI] and Patient Global Impressions [PGI] improvement scales) and remission (less than 9 on 6-week HAM-D-21) with both fluoxetine and placebo. Less anxiety/somatization was associated with favorable fluoxetine response, and lower levels of cognitive and sleep disturbance were associated with remission in the placebo group. By contrast, higher levels of psychomotor retardation in the placebo group were associated with clinician and patient ratings of much or very much improved. The similarities among responders in both groups may indicate that some in the fluoxetine group would have improved with placebo.

Aged↗

Relationship between early side effects and therapeutic effects of clomipramine therapy in obsessive-compulsive disorder.

Early adverse effects of a drug may be a manifestation of individual differences in drug metabolism or of different pathologic processes. These differences may influence therapeutic responsiveness. Using data from Ciba-Geigy's multicenter 10-week clinical trial, we studied the relationship between early side effects and subsequent therapeutic response to clomipramine (CMI) in obsessive-compulsive disorder. We used tabular analyses and multiple regression to evaluate associations between early complaints and change in score on the Yale-Brown Obsessive-Compulsive Scale. We also evaluated whether early complaints were drug related (i.e., true side effects). It appeared that dry mouth, constipation, dizziness, insomnia, male impotence, nervousness, palpitation, and tremor reported during the first 4 weeks were predictive of good response to CMI. Myoclonus and tinnitus appeared weakly associated with treatment success. Most of these complaints were reported more by the CMI group than the placebo group, and more during CMI treatment than before. The more common complaints may reflect an individual's ability to metabolize CMI appropriately so that adequate therapeutic blood levels are attained. The less common complaints may reflect a sensitivity to CMI's serotonergic actions.

Adult↗

Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group.

OBJECTIVE: Because physical illness may influence quality of life, we assessed its impact on functional status and treatment outcome in older depressed patients who participated in a clinical trial, which showed a significantly higher remission rate for fluoxetine over placebo (31.6% vs 18.6%, P < .001). DESIGN: Six-week, randomized, double-blind, placebo-controlled trial of fluoxetine, 20 mg daily. SETTING: Multiple clinical sites, both university and private. PARTICIPANTS: Outpatients (N = 671) were > or = 60 years (mean +/- SD = 67.7 +/- 5.7), met DSM-III-R criteria for unipolar major depression and had baseline scores > or = 16 on the Hamilton Depression Rating Scale. MEASUREMENTS: The 36-item short-form health survey (SF-36) was used to measure baseline and posttreatment functional health and well-being. Physical illness was rated by number of current chronic or historical illnesses. Change from baseline to endpoint in the Hamilton Depression Rating Scale total score was used to measure depression outcome. MAIN RESULTS: Most patients reported physical illness: 83% had one or more chronic illness, and 89% had one or more historical illness. Greater numbers of baseline chronic illness indicated worse physical functioning, general health perceptions, and vitality and greater bodily pain and role limitation from physical problems. Historical physical illness was associated with worse physical functioning, vitality, general health perceptions, social functioning, and mental health. Although the number of chronic illnesses did not influence treatment response, historical physical illness was associated with greater fluoxetine response and lower placebo response. CONCLUSIONS: These findings suggest that both current and previous physical illness are associated with lower quality of life in geriatric depression and that depressed older patients with chronic physical illness respond to antidepressants as well as those without such illness. Recovery from previous physical illness should be explored as a potential predictor of antidepressant treatment outcome.

Aged↗

A preliminary study of partial hospital management of severe obsessive-compulsive disorder.

OBJECTIVE: The study examined the effectiveness of a partial hospital treatment program combining behavioral therapy, medication, and psychosocial intervention for severe and treatment-resistant obsessive-compulsive disorder. METHODS: A total of 58 patients with a primary diagnosis of obsessive-compulsive disorder who underwent treatment in a partial hospital program were assessed at baseline, at program discharge, and at six-, 12-, and 18-month follow-ups. Obsessive-compulsive symptoms, depression, anxiety symptoms, and global functioning were rated. RESULTS: The majority of patients (71 percent) met the criterion for a successful outcome, which was a 25 percent decrease in score on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Fifty-five percent finished the program with YBOCS scores of 16 or less, indicating only mild symptoms. Most of these patients sustained their improvement at six, 12, and 18 months after discharge, and many showed further improvement with continued outpatient management. CONCLUSIONS: The partial hospital treatment program for obsessive-compulsive disorder appears to be an effective intervention that should be implemented and investigated further.

Adolescent↗

Risperidone augmentation of SRI treatment for refractory obsessive-compulsive disorder.

BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the mainstay of pharmacologic treatment for obsessive-compulsive disorder (OCD), many patients do not have an adequate response to these medications. One approach to treating SRI-refractory OCD patients has been to add other classes of medications to the SRI. We predicted that augmentation with risperidone would alleviate symptoms in SRI-refractory OCD patients. METHOD: 21 patients were treated openly with the combination of an SRI and adjunctive risperidone (mean dose = 2.75 mg/day). All met DSM-IV criteria for obsessive-compulsive disorder and had a variety of comorbid disorders. Prior to addition of risperidone, all patients had failed to respond to at least one adequate trial of an SRI. Response was determined by clinical judgment and standardized rating scales. RESULTS: 5 (24%) of the 21 patients experienced side effects (most commonly, akathisia), which forced discontinuation of risperidone. Of the 16 patients who tolerated combined treatment, 14 (87%) had substantial reductions in obsessive-compulsive symptoms within 3 weeks. Patients with horrific mental imagery had the strongest and fastest response, often within a few days. Patients with comorbid psychotic disorders improved gradually over 2 to 3 weeks. Patients with comorbid tic disorders had the poorest rate of response and highest rate of akathisia. CONCLUSION: These results suggest that risperidone augmentation is effective and well tolerated in patients with SRI-refractory obsessive-compulsive disorder. Response to risperidone augmentation appears to be influenced by symptom subtypes and comorbid conditions. Controlled trials are required to confirm the efficacy of risperidone augmentation for refractory OCD.

Adult↗

Use of receiver-operator characteristic (ROC) curve analysis to evaluate predictors of response to clomipramine therapy.

We used receiver-operator characteristic (ROC) curve analysis to evaluate predictors of response to clomipramine in obsessive-compulsive disorder (OCD). Previously, we identified response predictors among 230 OCD patients who received clomipramine in a placebo-controlled, multicenter clinical trail. We found that at baseline a later age of OCD onset, low scores on the Hamilton Depression scale, and high scores on items 3 and 8 of the Yale-Brown Obsessive Compulsive Scale predicted good response. Certain early side effects also predicted outcome. We fitted a logistic regression model containing baseline information and then calculated each patient's estimated response probability by substituting individuals' values in the regression equation. Next we compared the estimated response risks with each patient's known outcome. Finally, we produced a ROC curve by plotting the true positive and false positive rates for various cutoff points of the risk scores. The same steps were followed for Weeks 1 through 4, adding information about early side effects and weekly response. We found that baseline information predicted outcome better than chance, and predictive ability increased with data on side effects and early response.

Adult↗

Ambulatory monitoring of panic patients during regular activity: a preliminary report.

Ten patients with panic disorder and 10 matched control subjects were compared as to their blood pressure and heart rate during regular daily activity. Physiological responses were monitored by ambulatory recorder, and subjective reports of mood were collected. Data were analyzed controlling for activity and stress level of the subjects. Diastolic blood pressure emerged as a possible discriminatory factor between the groups. A trend for higher heart rate occurred in the panic group. In behavioral terms, panic patients tended to avoid anxiety-provoking situations, resulting in anxiety ratings comparable to those of the control group. Thus, recorded physiological differences between the groups may reflect heightened baseline autonomic activity in panic patients.

Activities of Daily Living↗

Brief cognitive-behavioral versus nondirective therapy for panic disorder.

Thirty panic disorder patients were assigned randomly to four weekly sessions of either cognitive-behavioral therapy or nondirective, supportive therapy. Dependent variables included clinician ratings, standardized self-report questionnaires, and self-monitoring. Cognitive-behavioral therapy led to significant reductions in worry about the recurrence of panic, and in overall ratings of phobic distress. Nondirective supportive therapy did not produce significant effects. In addition, proportionately more patients who were actively panicking at preassessment and underwent cognitive-behavioral treatment were free of panic after treatment. More than one third (38%) of patients who received cognitive-behavioral treatment were sufficiently improved that they withdrew from the pharmacological trial and/or did not meet criteria for panic disorder by the end of the four weeks.

Adult↗

Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression. Fluoxetine Collaborative Study Group.

BACKGROUND: We attempted to determine baseline characteristics predicting response in a 6-week, double-blind, geriatric depression trial, which showed a significantly higher remission rate for fluoxetine (20 mg daily) than for placebo (31.6% vs. 18.6%, p < .001). METHODS: Outpatients (N = 671) were 60 years or older (mean +/- SD = 67.7 +/- 5.7), met Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987) criteria for unipolar major depression, had baseline scores on the 17-item Hamilton Depression Rating Scale (HAMD17) of 16 or more, and were randomized after a 1-week placebo lead-in. Potential baseline predictors of percentage change in last-visit-carried-forward HAMD21 total scores were entered into a stepwise regression model. The sample was randomly divided into two groups (development and validation data sets) so that potential predictors could be confirmed in a second analysis. RESULTS: Of the 266 variables considered for their prognostic ability, 13 were found to be significant predictors using the development data set, including (a) presence of somatic complaints, absence of agitation, and presence of previous accidental injury for fluoxetine response; and (b) reported feelings of emptiness, absence of somatic complaints, and absence of early insomnia for placebo response. The second analysis using the validation data set failed to confirm statistical significance of predictors identified in the development data set. CONCLUSIONS: Although potentially useful baseline characteristics were initially identified as response predictors, conservative statistical methods failed to confirm any significant predictors of differential responses between fluoxetine and placebo in this double-blind, placebo-controlled trial. These results suggest that response predictor analyses require confirmation before conclusions can be generalized.

Aged↗

Screening for anxiety disorders in the primary care setting.

It is important to identify patients with anxiety disorders in the primary care setting so that they may be appropriately treated. The authors propose administration of a brief, 40-item screening instrument, the Four Dimensional Anxiety Scale (FDAS), to distinguish anxiety disorders from anxiety associated with medical conditions and from normal anxiety. For anxiety disorders patients, responses to five items on the FDAS Emotional dimension and 10 items on the Cognitive dimension differ significantly from medical patients or normals, and may help identify them. With such early identification and referral, medical costs of inappropriate care can be minimized, and human suffering can be alleviated through referral to a specialty anxiety disorders clinic.

Anxiety Disorders↗

Inert placebo versus active medication. Patient blindability in clinical pharmacological trials.

Patient blindability was examined in clinical, psychopharmacological, double-blind, placebo-controlled trials involving medications for obsessive-compulsive disorder and major depression. Based on the presence of clinical improvement and side effects, patients were able to determine correctly whether they took medication versus placebo. On the basis of these preliminary findings, the authors question the blindability of patients in clinical trials. Implications for the continued use of double-blind, placebo-controlled trials are discussed.

Clinical Trials as Topic↗

Predictors of treatment response in obsessive-compulsive disorder: multivariate analyses from a multicenter trial of clomipramine.

There have been many attempts to find predictors of the therapeutic response to the clomipramine treatment of obsessive-compulsive disorder. The majority of studies have failed to identify such predictors. Possible reasons for this failure include the small sample size of most studies, samples homogeneous with respect to the study factors of interest, and the use of statistical procedures that are insensitive to individual differences or that inadequately control for confounding. We have reanalyzed data from Ciba-Geigy's large, multicenter clinical trial of clomipramine for obsessive-compulsive disorder, using stratification and regression techniques to identify multiple prognostic factors and control for confounders. We assessed the relationship between therapeutic response and baseline measures such as severity of symptoms, type of symptoms (obsessions, compulsions, depression), length of illness, age of onset, and other demographic factors (age, race, and sex). We found age of onset to be a strong predictor of response to clomipramine: people who develop obsessive-compulsive disorder later in life have a better chance of responding than do those who become ill earlier, independent of length of illness. We also found that baseline depression is associated with response, but the association appears to be nonlinear.

Adolescent↗

Continuous physiological changes and subjective reports in panic patients: a preliminary methodological report.

Six panic disorder patients and six matched control subjects were studied using a new technique allowing continuous and simultaneous monitoring of physiological responses (blood pressure, heart rate, respiration) and subjective reports of anxiety and panic. This was done before, during, and after CO2 inhalation. Panic patients had significantly higher variability in their heart rate, blood pressure, and breathing rate than the control subjects. They also had irregular breathing patterns with frequent pauses. We identified three different patterns of response to CO2 inhalation in the panic patients. Some patients who panicked on CO2 showed a definite association between changes in physiological responses that preceded their subjective ratings of anxiety; however, others did not show this pattern. The possibility of different physiological mechanisms of panic in different patients is discussed.

Adolescent↗

Bupropion in the treatment of bipolar disorders: the same old story?

BACKGROUND: The treatment of bipolar disorders with mood stabilizing agents is complicated by breakthrough episodes of depression. Currently there are no consistently safe and effective medications for these episodes. The authors address the use of bupropion for this purpose. METHOD: Bupropion was added to the treatment regimens of 3 male and 8 female patients who had bipolar disorders as diagnosed by DSM-III-R criteria and were depressed and nonresponsive to current treatment. Ten of the 11 had previously cycled into manic episodes when treated with either a tricyclic antidepressant, fluoxetine, or phenelzine. RESULTS: Seven of the 11 patients had moderate-to-marked improvement after 6 weeks of treatment. A moderate-to-marked improvement continued in 4 of the 11 patients after a mean of 12 months of treatment (range, 0-20 months), justifying the continuation of bupropion. Baseline Global Assessment of Functioning scores, history of previous response to other antidepressants, treatment refractoriness, comorbid diagnoses, bipolar subtype, family history, cycle length, and demographics did not discriminate between bupropion responders and nonresponders. However, 6 of the 11 patients experienced manic or hypomanic episodes that necessitated discontinuation of bupropion. Five of the 6 patients who had manic episodes had been stabilized on lithium and carbamazepine or valproate prior to the addition of bupropion. CONCLUSION: These findings, based on consecutive cases, suggest that bupropion may pose the same risks as other antidepressants in precipitating manic episodes in depressed bipolar patients. The authors conclude that caution should be exercised when using bupropion in the treatment of bipolar disorders.

Adult↗