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Biomedical subjects

J W Stewart

Publications and source records attributed to J W Stewart.

At least 19 recordsLinked to original sources
PubMed2001

Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.

BACKGROUND: Recent reports suggest the value of electroencephalographic and dichotic listening measures as predictors of response to antidepressants. This study examines the potential of electroencephalographic alpha asymmetry and dichotic measures of perceptual asymmetry as predictors of clinical response to 12 weeks of treatment with fluoxetine (Prozac). METHODS: Resting electroencephalography (eyes open and eyes closed) and dichotic listening with word or complex tone stimuli were assessed in depressed outpatients during a pretreatment period. RESULTS: Fluoxetine responders (n = 34) differed from nonresponders (n = 19) in favoring left over right hemisphere processing of dichotic stimuli. They also differed in their resting electroencephalographic alpha asymmetry, particularly in the eyes open condition. Nonresponders showed an alpha asymmetry indicative of overall greater activation of the right hemisphere than the left, whereas responders did not. The relationship between hemispheric asymmetry and treatment response interacted with gender, being evident among depressed women but not men. CONCLUSIONS: The results are consistent with the hypothesis that a characteristic tendency toward greater left than right hemisphere activation is associated with favorable response to fluoxetine, whereas the opposite hemispheric asymmetry predicts poor response.

Adolescent↗
PubMed2001

Atypical and non-atypical subtypes of depression: comparison of social functioning, symptoms, course of illness, co-morbidity and demographic features.

BACKGROUND: There are scant data regarding the demographic and psychosocial characteristics of outpatients with Atypical Depression (AD). METHODS: The demographic characteristics, rates of chronic dysphoria, baseline Symptom Check List Revised, and Social Adjustment Scale scores of 320 moderately depressed patients with and without AD were compared. RESULTS: ADs had a higher number of self-reported symptoms, greater impairments in functioning, and higher rates of chronic dysphoria and bipolar II than patients without Atypical Depression (NAD). LIMITATIONS: Variables used in this study were mostly cross-sectional, and the analyses were performed post-hoc. CONCLUSIONS: These data suggest ADs had a more pernicious course of illness than NADs, and that patients with AD were more symptomatic and dysfunctional at admission.

Adult↗
PubMed2001

Pork with a high content of polyunsaturated fatty acids lowers LDL cholesterol in women.

BACKGROUND: Animal products contribute significantly to the saturated fat and cholesterol content of the American diet. Contrary to dietary advice, consumers have not limited their consumption of animal products. Thus, an alternative approach might be to modify the fatty acid composition of animal products. OBJECTIVE: We tested the hypothesis that modified pork with a high content of polyunsaturated fatty acids (PUFAs) and a low content of saturated fatty acids (SFAs) would lower plasma LDL-cholesterol concentrations in women. DESIGN: Twenty women aged 19-24 y completed a crossover study with 2 diets. Nutritionally complete diets containing 42% of energy from fat differed only in the inclusion of either standard or modified pork. Venous blood samples were collected at weeks 0, 4, and 8. RESULTS: The diet containing modified pork significantly lowered total plasma (P < 0.0076) and LDL (P < 0.0382) cholesterol. The modified diet also resulted in an increase in the PUFA and a decrease in the SFA and monounsaturated fatty acid contents of the cholesteryl ester, free fatty acid, phospholipid, and triacylglycerol lipid classes in both plasma and erythrocytes. Plasma concentrations of glucose, insulin, triacylglycerol, and free fatty acids did not change significantly. CONCLUSIONS: Consumption of pork with a high PUFA content resulted in a decrease in the subjects' total plasma and LDL cholesterol and shifted the fatty acid composition from SFAs to PUFAs in the plasma and erythrocytes. Modification of the fatty acid composition of animal foods will be a useful approach to lowering the saturated fat consumption of Americans.

Adult↗
PubMed2000

A method to quantify rater bias in antidepressant trials.

Some studies indicate that the blind in clinical trials of the efficacy of antidepressant drugs is less than perfect. It has been suggested that, as a consequence of this incomplete blind, biased raters inflate efficacy and that, in fact, these drugs are relatively ineffective. However, in the literature, we could find no prior attempt to quantify rater bias and, thus, measure its contribution to claims of antidepressant efficacy. We used the distribution of SCL-90 (Symptom Check List) depression scale scores to derive a patient-based effect size, and contrasted this with the clinician-based effect size. We propose the difference between these two effect sizes (patient self-rating and clinician-derived) to be an indirect measure of bias. If patients had a prodrug bias, this method would be invalid. However the response rate from studies with active placebo suggest a patient prodrug bias is unlikely. The effect sizes derived from patient self-ratings are smaller than those derived from clinician ratings. This allows for the possibility that some clinician ratings were biased. However, quantifying the effect of bias suggests that it was insufficient to invalidate the original study conclusions based on clinician ratings, because the proportion of responders, based on patient self-ratings, differed significantly between the two drugs and placebo. Their 95% confidence intervals (CI) did not overlap. This analysis allows that some clinician ratings may be biased. However, the extent of bias appears insufficient to alter conclusions based on clinician ratings regarding efficacy of antidepressant drugs in this trial. Application of our approach in other trials is necessary to establish generalizability.

Antidepressive Agents↗
PubMed2000

Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women.

BACKGROUND: No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women. OBJECTIVE: Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the menopausal transition. DESIGN: Perimenopausal subjects were randomly assigned, double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor soy (SPI-; n = 24), or whey (control; n = 21) protein. At baseline and posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline, midtreatment, and posttreatment, urinary N:-telopeptides and serum bone-specific alkaline phosphatase (BAP) were measured. RESULTS: The percentage change in lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or SPI- groups, but loss occurred in the control group (-1.28%, P: = 0.0041; -1.73%, P: = 0.0037). By regression analysis, SPI+ treatment had a positive effect on change in BMD (5.6%; P: = 0.023) and BMC (10.1%; P: = 0.0032). Baseline BMD and BMC (P: < or = 0.0001) negatively affected the percentage change in their respective models; baseline body weight (P: = 0.0036) and bone-free lean weight (P: = 0.016) contributed positively to percentage change in BMD and BMC, respectively. Serum BAP posttreatment was negatively related to percentage change in BMD (P: = 0.0016) and BMC (P: = 0.019). Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones, not soy protein, exerted the effect. CONCLUSION: Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women.

Adult↗
PubMed2000

A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression.

OBJECTIVE: The atypical subtype of depression appears to be both well validated and common. Although monoamine oxidase inhibitors are effective in treating atypical depression, their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment. The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor (SSRI) fluoxetine in the treatment of major depression with atypical features. METHOD: One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were randomly assigned to receive fluoxetine, imipramine, or placebo for a 10-week clinical trial. Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group. RESULTS: In both intention-to-treat and completer groups, the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo. The two medications did not differ from each other in effectiveness. Significantly more patients dropped out of treatment with imipramine than with fluoxetine. Before treatment, patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions, compared with population norms. The self-ratings of patients who responded to treatment essentially normalized on these measures. CONCLUSIONS: Despite earlier data that SSRIs might be the treatment of choice, fluoxetine appeared to be no better than imipramine in the treatment of atypical depression, although fluoxetine was better tolerated than imipramine.

Adolescent↗
PubMed2000

Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design.

OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium. METHOD: Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase. RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex. CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.

Adolescent↗
PubMed2000

Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: effects on personality.

OBJECTIVE: Although previous studies have shown that dysthymia, or chronic depression, commonly responds to antidepressant medications (with improvements in depressive symptoms and psychosocial functioning), there have been no systematic studies of the impact of antidepressant treatment on personality variables in patients with this disorder. METHOD: In a multicenter study, 410 patients with early-onset primary dysthymia were treated in a randomized prospective fashion with sertraline, imipramine, or placebo. The data were analyzed in terms of the subjects' scores on the Tridimensional Personality Questionnaire, a 100-item self-report instrument that measures four temperamental dimensions: harm avoidance, reward dependence, novelty seeking, and persistence. RESULTS: At baseline, the harm avoidance scores of the dysthymic subjects were approximately 1.5 standard deviations higher than those of a previously reported community sample. After treatment, there was a significant decrease in harm avoidance scores, with no significant between-group differences. Remission of dysthymia was associated with significantly greater improvement in harm avoidance, with the greatest numerical change found in the patients treated with sertraline. Subjects' Tridimensional Personality Questionnaire scores were correlated at a 0.50 level with the Social Adjustment Scale both pre- and posttreatment, suggesting that a high degree of harm avoidance may be associated with poor social functioning. CONCLUSIONS: Before treatment, chronically depressed patients demonstrate an abnormality in temperament, as measured by elevated degrees of harm avoidance. Remission of dysthymia is associated with improvement in this aspect of temperament.

Adult↗
PubMed2000

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.

Adult↗
PubMed1999

Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: a dichotic listening study.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.

Adult↗
PubMed1999

Do tricyclic responders have different brain laterality?

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear x Test x Treatment x Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controls. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.

Antidepressive Agents, Tricyclic↗
PubMed1998

Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo.

BACKGROUND: Delayed and persistent ("true drug") improvement characterizes the response to antidepressant medication. Early or nonpersistent ("placebo") benefit is typical of a placebo response. The prediction was that patients with a true drug response would sustain their benefit best if they continued to receive the drug and that patients with a placebo response would have an equivalent prognosis whether they continued to receive the drug or were switched to placebo. METHODS: Patients with major depression who met the study's response criteria (a modified Hamilton Depression Rating Scale score < or =7 and failure to meet major depression criteria after each of the last 3 weeks following 12 to 14 weeks of treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week randomized placebo substitution trial during which the return of depressive symptoms defined relapse. The timing and persistency of response during initial treatment defined true drug or placebo response patterns. RESULTS: Patients with a true drug response pattern relapsed significantly more frequently if they were switched to placebo than if they continued to receive fluoxetine (P<.001 for weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a placebo response pattern had an equivalent outcome whether maintained on fluoxetine therapy or placebo (P< .20 for weeks 12-26, test invalid for weeks 26-50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed more often when they continued to receive fluoxetine than patients with a true drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36 for weeks 50-62). CONCLUSIONS: These findings confirm that pattern analysis validly differentiates true drug from nonspecific initial responses and extend its use to the continuation and maintenance phases of treatment for depression. Investigations into the mechanisms of antidepressant activity might best be limited to those that can account for delayed efficacy. Fluoxetine's efficacy during the continuation and maintenance phases of treatment may be limited to patients with a true drug pattern of initial response.

Adolescent↗
PubMed1998

Social functioning and residual symptomatology among outpatients who responded to treatment and recovered from major depression.

It is unclear whether depressed patients who respond to treatment, and subsequently recover, manifest a significant degree of residual symptomatology and enduring psychosocial impairment. The purpose of this study was to compare the social functioning and symptoms of depressed outpatients who responded to acute treatment, and had a sustained recovery from major depression for 6 months, with psychiatrically normal community samples. The sample (n = 48) was drawn from the NIMH Treatment of Depression Collaborative Research Program. The Social Adjustment Scale scores and the Symptom Check List of recovered patients were clinically indistinguishable from the community sample scores. These data suggest that patients who benefit from acute treatment and recover from major depression can expect to achieve a normal level of functioning and symptomatology.

Adult↗
PubMed1998

Atypical features and treatment response in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

Because depression with atypical features is poorly responsive to imipramine, treatment trials including a tricyclic antidepressant arm should assess depressive subtype. Sotsky and Simmens had previously reanalyzed data from the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP) providing independent confirmation that imipramine is ineffective for patients with atypical features. The TDCRP was a 16-week study in which 239 outpatients with major depression were randomly assigned to cognitive behavior therapy (CBT), interpersonal psychotherapy (IPT), imipraminecase management (IMI-CM), or pill placebo-case management (Pbo-CM). We used Sotsky and Simmens' algorithm to investigate the effect of diagnostic subtype on all four treatments. Hierarchical multiple regression analyses demonstrated IMI-CM benefit relative to Pbo-CM in patients without but not in those with atypical features. These analyses did not demonstrate differential psychotherapy efficacy between depressive subtypes. In conclusion, subsequent analyses of the TDCRP study demonstrated the need to identify the subgroup of depressed patients who have atypical features. Failure to identify this subtype underestimates imipramine's benefit in the appropriately treated subgroup. Comparisons of other treatments with imipramine may be misleading if they do not account for diagnostic subtype.

Algorithms↗
PubMed1998

Placebo run-in period in studies of depressive disorders. Clinical, heuristic and research implications.

BACKGROUND: In spite of the virtually ubiquitous nature of the initial 10-day placebo run-in period (IPR) in drug trials, there is little empirical data establishing its relevance. METHOD: Data from 593 subjects were examined retrospectively to determine whether or not the prognosis of subjects minimally improved during the IPR was different to those who were unimproved. The IPR period was single-blind and was followed by a six-week double-blind phase in all studies. RESULTS: Twenty-six per cent of the subjects were minimally improved and 74% were unimproved. Approximately 10% of the subjects who were much improved were not followed systematically. Across a range of diagnosis, severity and chronicity subjects minimally improved (versus unimproved) after IPR had a more favourable prognosis whether assigned to drug or placebo. CONCLUSIONS: Change during IPR appears to be a meaningful predictor. Stratification should be considered in future antidepressant studies.

Adolescent↗