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Biomedical subjects

A J Rush

Publications and source records attributed to A J Rush.

At least 55 records · Page 3Linked to original sources
PubMed2000

Flexible treatment strategies in chronic disease: clinical and research implications.

Multiple treatments are available for nearly all the mood disorders. This range of treatment options adds a new dimension of choice to clinical decision making. In addition to prescribing the best initial treatment, clinicians should have an algorithm for deciding if and when to make subsequent changes in treatment to take advantage of second-line treatment options when necessary. This article aims to 1) show that a wide variety of clinical decisions can be framed as choices among adaptive (within-patient) threshold-based strategies or algorithms, illustrating the generality of the concept; 2) illustrate two ways to design randomized clinical trials to compare treatment strategies with each other to decide which strategy is best; and 3) discuss some of the advantages offered by these designs, in terms of both patient acceptability and adherence to experimental protocols.

Algorithms↗
PubMed2000

Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls.

The amplitude and time course of slow-wave activity (SWA) during NREM sleep were compared in 76 outpatients with depression and 55 healthy control subjects. Lower SWA amplitude was evident in the depressed group, especially among depressed men. For the most part, significant differences between patients and control subjects were restricted to the first NREM period and only in those 20-30 years of age. Significant age-related declines in SWA amplitude were evident in control subjects but not in depressed patients. In addition, sex differences in the depressed group were twice as large as those seen in control subjects. The time course of SWA amplitude, presumed to reflect homeostatic sleep regulation of SWA, was only abnormal in depressed men with lower accumulation and slower dissipation over NREM sleep. Depressed women showed no evidence of an abnormal SWA time course. Furthermore, no sex differences in the time course of SWA were evident in control subjects, and age-related changes in this aspect of regulation were not striking in any group. Thus, the amplitude of SWA showed strong age effects in healthy individuals but not in those with MDD whereas the time course showed very subtle age effects. It was suggested that men, but not women, with MDD show impaired SWA regulation that is evident from 20 to 40 years of age. These findings provide further support that the pathophysiology of depression differs for men and women and suggest that maturational effects on SWA in depression differ from those observed in healthy individuals.

Adult↗
PubMed2000

Slow-wave activity during non-REM sleep in men with schizophrenia and major depressive disorders.

Both major depressive disorders (MDD) and schizophrenia (SZ) have been associated with reductions in slow-wave (Stages 3 and 4) sleep, although these findings are controversial. The present study compared quantitative EEG measures of slow-wave activity (0.5-4 Hz) during non-REM (NREM) sleep among age-matched, symptomatic but unmedicated, depressed, schizophrenic and healthy control men (n=13/group). The amplitude of slow-wave activity (SWA) in the first NREM sleep period was significantly lower in both the MDD and SZ groups compared with controls. However, the time course of SWA, its accumulation and dissipation over all NREM sleep time, was abnormal in the MDD group but not in those with SZ. These findings suggest that the regulation of SWA is impaired in men with MDD but not in SZ. Thus, although those with SZ show reduced amplitude SWA in the first NREM period, there is no evidence that homeostatic regulation of SWA is impaired in this psychiatric group.

Adult↗
PubMed2000

Temporal characteristics of delta activity during NREM sleep in depressed outpatients and healthy adults: group and sex effects.

STUDY OBJECTIVES: The primary aim was to evaluate group and sex differences in delta activity across non-rapid eye movement (NREM) sleep in depressed patients and healthy controls. DESIGN: Repeated-measures ANOVA contrasted delta power, amplitude and incidence in the first three NREM periods (stages 2, 3, and 4) of sleep. The time course of delta activity was evaluated with exponential regressions. Age effects on delta were evaluated with linear regression analysis. SETTING: Two consecutive nights were spent in the laboratory, the first of which served as adaptation. PATIENTS OR PARTICIPANTS: Twenty-two (9 men, 13 women) symptomatic, but unmedicated, outpatients with major depressive disorder (MDD) and 23 healthy controls (15 men, 8 women) participated in the study. MEASUREMENTS AND RESULTS: Delta power and amplitude showed significant group by sex interactions. Men with MDD showed lower power and amplitude in NREM sleep compared to women with MDD, but did not differ significantly from controls. However, the time course of delta power and amplitude was significantly different in men with MDD, with lower accumulation and slower dissipation across NREM sleep than all other groups. Women with MDD showed no evidence of lower delta power and amplitude or an abnormal time course compared to control women or men. Age had a differential influence on delta activity between the groups, with little age-related change in delta activity in the depressed groups. CONCLUSIONS: It was concluded that slow-wave sleep deficiencies may be characteristic of men, but not women, with MDD. It was also concluded that the influence of age on delta activity varied as a function of both psychiatric status and sex.

Adolescent↗
PubMed2000

A comparison of alternative assessments of depressive symptom severity: a pilot study.

This study compared the performance of an itemized symptom self-report (Inventory of Depressive Symptomatology - Self-Report; IDS-SR), patient global ratings, and clinician global ratings with an itemized clinician-rated symptom severity measure (Inventory of Depressive Symptomatology - Clinician-Rated; IDS-C) in detecting treatment effects in patients with major depressive disorder (MDD). A total of 28 inpatients (30.8% psychotic) and 34 outpatients (17.9% psychotic) with MDD began treatment that followed the Texas medication algorithm. The clinicians completed the IDS-C and a Physician Global Rating Scale (PhGRS) at each assessment visit, while the patients completed the IDS-SR and a Patient Global Rating Scale (PtGRS). Change scores from the baseline to subsequent weeks were computed for all subjects, utilizing all four measures. The IDS-SR was a significant independent predictor of the response to treatment as compared to the two global ratings. The IDS-SR was as sensitive to change as the IDS-C. While the clinician-rated itemized symptom severity rating scale remains the standard to assess the symptomatic outcome of the treatment of MDD, a self-report of identical symptomatology may be a reasonable alternative for many patients.

Adult↗
PubMed2000

Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study.

BACKGROUND: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness. METHODS: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence. RESULTS: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence. CONCLUSIONS: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.

Adolescent↗
PubMed2000

Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents.

BACKGROUND: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression. METHODS: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents). RESULTS: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls. CONCLUSIONS: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.

Activity Cycles↗
PubMed2000

Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study.

BACKGROUND: Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. METHODS: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. RESULTS: In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS(28)) scores averaged 38.0. Response rates (> or =50% reduction in baseline scores) were 40% for both the HDRS(28) and the Clinical Global Impressions-Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. CONCLUSIONS: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions.

Adolescent↗
PubMed2000

Vagus nerve stimulation: a new tool for brain research and therapy.

Biological psychiatry has a long history of using somatic therapies to treat neuropsychiatric illnesses and to understand brain function. These methods have included neurosurgery, electroconvulsive therapy, and, most recently, transcranial magnetic stimulation. Fourteen years ago researchers discovered that intermittent electrical stimulation of the vagus nerve produces inhibition of neural processes, which can alter brain electrical activity and terminate seizures in dogs. Since then, approximately 6000 people worldwide have received vagus nerve stimulation for treatment-resistant epilepsy. We review the neurobiology and anatomy of the vagus nerve and provide an overview of the vagus nerve stimulation technique. We also describe the safety and potential utility of vagus nerve stimulation as a neuroscience research tool and as a putative treatment for psychiatric conditions. Vagus nerve stimulation appears to be a promising new somatic intervention that may improve our understanding of brain function and has promise in the treatment of neuropsychiatric disorders.

Brain↗
PubMed2000

Vagus nerve stimulation. A potential therapy for resistant depression?

VNS builds on a long history of investigating the relationship of autonomic signals to limbic and cortical function and is one of the newest methods to physically alter brain function. VNS is a clinically useful anticonvulsant therapy in treatment resistant patients with epilepsy, and pilot data suggest that it has potential as an antidepressant therapy. The known anatomic projections of the vagus nerve suggest that VNS also might have other neuropsychiatric applications. Additional research is needed to clarify the mechanisms of action of VNS and the potential clinical utility of this intriguing new somatic portal into the CNS.

Brain Mapping↗
PubMed2000

Clinician, parent, and child prediction of medication or placebo in double-blind depression study.

To evaluate how well a blind is maintained in a double-blind study. Clinicians (n = 66), parents (n = 62), and depressed child/adolescent subjects (n = 62) predicted whether the patient had been on either placebo or active medication at the end of an eight-week double-blind placebo versus fluoxetine trial. Clinician, patient and parents' guesses as to which treatment they had received were at a chance level based on an overall analysis. However, when clinical response and condition assignment were controlled, all were correctly predicting placebo treatment but not medication treatment. The finding that subjects, parents and clinicians predict at a chance level is important for double-blind study design integrity. However, clinicians, parents and subjects were accurately predicting placebo treatment when clinical response and the assigned condition were taken into account but not medication. Since they do not know condition however, all remain essentially blinded, and this is an important finding for design and analysis integrity for double-blind studies.

Adolescent↗
PubMed2000

Vagus nerve stimulation is associated with mood improvements in epilepsy patients.

Vagus nerve stimulation (VNS) has gained increasing acceptance for treatment of drug-resistant seizures. The aim of this study was to evaluate effects of VNS on depressed mood in epilepsy patients during the first 6 months after implantation of the stimulation device. This study was conducted as an addition to the international multisite randomized and double-blind controlled trial on anti-seizure effects of VNS (EO3). Only adult patients with >4/month medication-resistant complex-partial seizures were included (N=11). During the acute phase of the study (3 months after implantation), patients were randomly assigned to low (stimulation detection) versus high stimulation (maximal tolerability, maximum 1.75 mA). Mood and mood changes were recorded based on standardized psychiatric rating scales and self-report questionnaires. Patients were assessed 4 weeks before (baseline) as well as 3 and 6 months after implantation. Significant positive mood effects were observed in most scales and subscales at the 3-month follow-up (P<0.05). Mood improvements were sustained at the 6-month follow-up and were independent of effects on seizure activity (9/11 mood responders versus 2/11 seizure responders). Mood effects appeared more pronounced in the high stimulation group after the acute study phase, but findings were not significant (P<0.10). VNS is associated with mood improvements in patients with epilepsy, but to confirm VNS dose effects, studies with more statistical power are needed.

Adult↗
PubMed2000

Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM-p) for longitudinal assessment of bipolar illness.

BACKGROUND: Systematic and accurate depiction of a patient's course of illness is crucial for assessing the efficacy of maintenance treatments for bipolar disorder. This need to rate the long-term prospective course of illness led to the development of the National Institute of Mental Health prospective Life Chart Methodology (NIMH-LCM-p or LCM). The NIMH-LCM-p allows for the daily assessment of mood and episode severity based on the degree of mood associated functional impairment. We have previously presented preliminary evidence of the reliability and validity of the LCM, and its utility in clinical trials. This study is a further and more extensive validation of the clinician rated NIMH-LCM-p. METHODS: Subjects included 270 bipolar patients from the five sites participating in the Stanley Foundation Bipolar Network. Daily prospective LCM ratings on the clinician form were initiated upon entry, in addition to at least monthly ratings with the Inventory of Depressive Symptomatology-clinician rated (IDS-C), the Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). We correlated appropriate measures and time domains of the LCM with the IDS-C, YMRS and GAF. RESULTS: Severity of depression on the LCM and on the IDS-C were highly correlated in 270 patients (r = -0.785, P < 0.001). Similarly, a strong correlation was found between LCM mania and the YMRS (r = 0.656, P < 0.001) and between the LCM average severity of illness and the GAF (r = -0.732, P < 0.001). CONCLUSIONS: These data further demonstrate the validity and potential utility of the NIMH-LCM-p for the detailed daily longitudinal assessment of manic and depressive severity and course, and response to treatment.

Adult↗
PubMed2000

Structured interview and uniform assessment improves diagnostic reliability.

OBJECTIVE: To compare a Childhood Uniform Assessment Package (CUAP), including a computerized structured diagnosis, with routine assessment and treatment in public mental health settings. DATA SOURCES/STUDY SETTINGS: Data was collected prospectively on 250 children and adolescents in both public mental health inpatient and outpatient settings in a large metropolitan area and a rural area. STUDY DESIGN: Subjects were randomized to either routine assessment and treatment as usual (ATU) or ATU plus an additional "gold standard" assessment battery Childhood Uniform Assessment Package (CUAP). Outcome measures were taken at admission (baseline), discharge, and again 6 months later. METHODS: The study was conducted at a State Hospital (CUAP, n = 75; ATU, n = 75) and a Community Mental Health center (CUAP, n = 50; ATU, n = 50). The "gold standard" diagnostic process was established at the Children's Medical Center-Dallas. Research focused on a comparison of the CUAP diagnostic process to the existing diagnostic process (ATU) and the service delivery system of an inpatient and outpatient public sector clinical treatment setting. PRINCIPAL FINDINGS: A bachelor's level individual can be trained to administer a highly reliable diagnostic battery to meet a "gold standard," suggesting a possible cost-effective way to assist in diagnostic evaluations. Higher reliability was found between this standardized assessment package (CUAP) and inpatient physicians than for outpatient physicians. The highest interrater reliabilities were found for attention deficit and substance abuse disorders, less so for the other behavior disorders. The use of CUAP results in more reliable diagnoses in public settings than those provided by typical clinical staff by identifying mood and anxiety disorders (disorders with the lowest reliability) with better reliability. The addition of "gold standard" diagnostic assessments (CUAP) did not appear to affect length of stay, number of medication changes, use of seclusion or restraints, and other behavioral interventions in the inpatient setting. Outpatient follow-up services did not differ for CUAP versus ATU either. CONCLUSIONS: A standard uniform assessment package that includes a structured diagnostic instrument can improve overall diagnostic reliability but may not have a significant overall impact in clinical treatment strategies or outcomes without additional intervention to assure proper use of the information. A well-trained bachelor's level assistant can administer such a battery.

Adolescent↗
PubMed2000

Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder.

OBJECTIVE: To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years. METHOD: Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS). RESULTS: Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen. CONCLUSIONS: Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.

Acute Disease↗
PubMed2000

Methods to improve diagnostic accuracy in a community mental health setting.

OBJECTIVE: This study determined the extent to which adding structured procedures improved diagnostic accuracy for outpatients with severe mental illness in a community mental health setting. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research nurse reviewed medical records and amended the SCID diagnoses accordingly. A research psychiatrist or psychologist reviewed the diagnostic data and interviewed each patient to verify or further modify the previous findings. Diagnostic outcomes at each step of the procedure were compared to determine whether adding additional data improved diagnostic accuracy. The additional time required for each element of the diagnostic procedure was also assessed. RESULTS: Kappa comparisons of the different diagnostic levels showed that adding additional data significantly improved accuracy. Diagnoses rendered by combining the SCID and review of the medical record were the most accurate, followed by the SCID alone, and then diagnoses made by psychiatrists during routine care. In addition, the SCID alone identified five times as many current and past secondary diagnoses as were documented routinely in patients' charts. CONCLUSIONS: Combining structured interviewing with a review of the medical record appears to produce more accurate primary diagnoses and to identify more secondary diagnoses than routine clinical methods. The patients' knowledge of their diagnoses was limited, suggesting a need for patient education in this setting. Whether use of structured interviewing in routine practice improves patient outcomes deserves further study.

Adolescent↗
PubMed2000

The Texas Medication Algorithm Project Patient and Family Education Program: a consumer-guided initiative.

Educating patients with mental illness and their families about the illness and its treatment is essential to successful medication (disease) management. Specifically, education provides patients and families with the background they need to participate in treatment planning and implementation as full "partners" with clinicians. Thus, education increases the probability that appropriate and accurate treatment decisions will be made and that a treatment regimen will be followed. The Texas Medication Algorithm Project (TMAP) has incorporated these concepts into its philosophy of care and accordingly created a Patient and Family Education Program (PFEP) to complement the utilization of medication algorithms for the treatment of schizophrenic, bipolar, and major depressive disorders. This article describes how a team of mental health consumers, advocates, and professionals developed and implemented the PFEP. In keeping with the TMAP philosophy of care, consumers were true partners in the program's development and implementation. They not only created several components of the program and incorporated the consumer perspective, but they also served as program trainers and advocates. Initially, PFEP provides basic and subsequently more in-depth information about the illness and its treatment, including such topics as symptom monitoring and management and self-advocacy with one's treatment team. It includes written, pictorial, videotaped, and other media used in a phased manner by clinicians and consumer educators, in either individual or group formats.

Algorithms↗