Biomedical subjects

P T Trzepacz

Publications and source records attributed to P T Trzepacz.

At least 19 recordsLinked to original sources

PubMed2001

The central cholinergic system profile of olanzapine compared with placebo in Alzheimer's disease.

OBJECTIVE: The objective of this analysis was to compare the treatment-emergent central anticholinergic-like adverse events experienced during treatment with olanzapine versus placebo in patients with psychosis and/or agitation due to Alzheimer's disease (AD). In addition, changes in cognition were assessed in a subgroup of patients with mild to moderate cognitive impairment. METHODS: Double-blind data were compared for placebo and three fixed olanzapine dosages (5 mg/day, 10 mg/day, and 15 mg/day) in 206 nursing home-residing patients with AD for five a priori selected central nervous system anticholinergic-like adverse events: confusion, delirium, delusions, hallucinations, abnormal thinking. Mean change from baseline to endpoint on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) was measured for a subgroup of 43 patients who had mild to moderate cognitive impairment at baseline. RESULTS: There were no significant differences in central anticholinergic-like adverse events at any olanzapine dose compared to placebo. Additionally, in the 43-patient subgroup, there were no significant differences in mean change in ADAS-Cog scores between placebo and the three olanzapine dose subgroups. CONCLUSION: Olanzapine did not differ significantly from placebo for any of the five central nervous system anticholinergic events nor on the ADAS-Cog. Olanzapine's initially reported potent in vitro muscarinic receptor affinity is not consistent with this clinical study of central nervous system anticholinergic-like adverse events in patients with AD.

Aged↗

PubMed2001

Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium.

The DRS-R-98, a 16-item clinician-rated scale with 13 severity items and 3 diagnostic items, was validated against the Cognitive Test for Delirium (CTD), Clinical Global Impression scale (CGI), and Delirium Rating Scale (DRS) among five diagnostic groups (N=68): delirium, dementia, depression, schizophrenia, and other. Mean and median DRS-R-98 scores significantly (P<0.001) distinguished delirium from each other group. DRS-R-98 total scores correlated highly with DRS, CTD, and CGI scores. Interrater reliability and internal consistency were very high. Cutoff scores for delirium are recommended based on ROC analyses (sensitivity and specificity ranges: total, 91%-100% and 85%-100%; severity, 86%-100% and 77%-93%, respectively, depending on the cutoffs or comparison groups chosen). The DRS-R-98 is a valid measure of delirium severity over a broad range of symptoms and is a useful diagnostic and assessment tool. The DRS-R-98 is ideal for longitudinal studies.

Adolescent↗

PubMed2000

Relationship between symptoms and motoric subtype of delirium.

For 46 patients with delirium who were consecutive referrals to a consultation-liaison psychiatry service, the authors describe the relationships between symptoms, as rated on the Delirium Rating Scale, and delirium motoric subtypes, as defined by Liptzin and Levkoff's criteria. Most cases were of the mixed subtype (46%), 24% were hypoactive, and 30% were hyperactive. Overall scores differed significantly among motoric subtype groups, being highest in the hyperactive, lowest in the hypoactive, and intermediate in the mixed. On item scores, the hypoactive group scored lower than the hyperactive group for delusions, mood lability, sleep-wake cycle disturbances, and variability of symptoms, but lower than the mixed group only for mood lability. The results suggest that delirium presents as motoric subtypes that differ according to symptom profile and severity of delirium. These subtypes may differ in their underlying pathophysiologies, responsiveness to therapeutic interventions, and outcome.

Adult↗

PubMed2000

Motoric subtypes of delirium.

Delirium is a common neuropsychiatric disorder with wide ranging symptoms and significant morbid impact. Disturbances of motor behavior are an important feature of delirium and form the basis for the most commonly studied clinical subtype. This article reviews the relevance of motoric disturbance to delirium phenomenology and discusses possible neurobiological causes for different presentations of motor behavior in delirium. Evidence is presented to support the usefulness of using motorically defined subtypes based on identified differences according to underlying origins, pathophysiologies, responsiveness to therapy and natural course. Methodological issues relating to motoric subtype studies are addressed and suggestions for future research are made.

Aged↗

PubMed2000

Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine.

This article reviews the literature relevant to improving our understanding of the neural underpinnings of delirium. That the characteristic symptoms of delirium occur as a result of a wide diversity of causes supports the concept of a ""final common pathway. " What constitutes this may involve certain brain regions or circuits and certain neurotransmitters. Neuroanatomical data derived from neuroimaging and lesion reports suggest the importance of pathways in prefrontal cortex, thalamus, fusiform cortex, posterior parietal cortex, and basal ganglia. Neurotransmitters most implicated in delirium that could be candidates to mediate the characteristic symptoms of delirium, as well as the electroencephalogram changes, are acetylcholine and dopamine. Acetylcholine deficiency and dopamine excess---absolute and/or relative to each other---appear to be critical in the final common pathway. These neurotransmitters affect each other, depending on the receptor subtype, and their receptor distribution among layers of cortex in areas such as prefrontal cortex and temporal lobe suggests that cholinergic and dopaminergic neurons could interact with each other during delirium. Electroconvulsive therapy is described as a special situation in which excess dopamine and delirium may have a therapeutic effect on depression recovery, in contrast with the usual association of delirium with negative effects.

Acetylcholine↗

PubMed1998

Is delirium different when it occurs in dementia? A study using the delirium rating scale.

The authors studied 61 geropsychiatric patients with delirium from a cohort of 843 consecutive admissions to a geriatric clinical research unit. A central study goal was to assess how the presence of dementia affected the presentation of delirium. Eighteen delirious (D) and 43 delirious-demented (D-D) patients were compared on the Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and EEG. D-D patients had lower MMSE scores, but no differences were found in total DRS or BPRS scores or in EEG grade. DRS items were similar in the two groups except that D-D had more cognitive impairment than D. An exploratory principal components analysis of DRS items identified two core factors. The authors conclude that the presentation of delirium in the setting of concurrent dementia is very similar to delirium without dementia, with subtle differences probably attributable to dementia.

Aged↗

PubMed1998

Relationship between etiology and phenomenologic profile in delirium.

This study describes the symptom profile of 46 patients with delirium seen as consecutive referrals to a consultation-liaison psychiatry service. The relationship between symptoms rated on the Delirium Rating Scale (DRS) and delirium subtypes defined according to three putative etiologic groups are described. The relationship between etiologic groups and motoric subtype of the delirium episode is also described. Drug-related cases had the highest total DRS score and higher scores than the anticholinergic group for perceptual changes, delusions, psychomotor disturbance, and mood lability. Drug-related cases had higher scores than both the anticholinergic and infectious/electrolyte group for changes in sleep-wake cycle and fluctuation of symptoms. Those from the anticholinergic etiologic group were more likely to fit the hypoactive motoric subtype. Although our findings are tentative, etiologic categories may present with different symptom profiles, which may be associated with differing treatment responsiveness and course.

Adult↗

PubMed1998

Delirium phenomenology illuminates pathophysiology, management, and course.

The phenomenology of delirium has received little standardized longitudinal study but offers the prospect of valuable insights regarding clinical subtypes, differentiation from other neuropsychiatric disorders, identification of underlying pathophysiologies, management, and course. This review examines current approaches to the investigation of delirium phenomenology and how the findings to date illuminate our understanding of delirium. It concludes with recommendations for future investigations.

Aged↗

PubMed1997

Serious overdosers admitted to a general hospital: comparison with nonoverdose self-injuries and medically ill patients with suicidal ideation.

There are few psychiatric studies of serious self-injury patients admitted to general hospitals. In order to better characterize patients whose overdoses are serious enough to require hospitalization on a toxicology service, we describe 207 consecutively admitted, serious overdose patients (OD), all of whom were psychiatrically evaluated. They were compared with 53 nonoverdose self-injury cases (NO) and 79 medical/surgical patients with suicidal ideation (SI) who were routinely referred for consultation during the same 2-year period. All data were contemporaneously compiled into a computerized database and analyzed. The attempters (OD and NO) were younger than the ideation patients (SI). The OD group was predominantly female (60%) and the NO and SI groups were predominantly male (72%). More OD cases were separated and more SI cases were widowed. Similar to previous reports, prior psychiatric contact was high in all groups. DSM-III-R diagnoses of depression, adjustment disorders, and substance abuse were most common in each group, without group differences. Only borderline personality disorder distinguished the groups, and the OD group had significantly more borderline patients. There were no seasonal differences for admission dates between groups, SI cases had longer hospital lengths of stay and were least likely to require further psychiatric care after discharge from the general hospital. Attempter groups were more similar to each other than the ideation patients. Clinicians should maintain a high index of suspicion for Axis I disorders in suicidal general hospital patients, though female borderline patients are particularly associated with the serious overdose method.

Adjustment Disorders↗

PubMed1996

Prospective study of FK506 side effects: anxiety or akathisia?

FK506 is a macrolide immunosuppressant agent used in solid organ and bone marrow transplantation and for autoimmune disorders. FK506 is reported to have a number of neuropsychiatric side effects, including anxiety and tremor. Because FK506 was implicated in causing akathisia in a case report, we did a prospective, cross-sectional study of 25 renal transplant recipients to determine whether akathisia occurred and/or had a relationship to FK506 plasma levels. The Symptom Checklist-90-R, Hamilton Anxiety (HAM-A), and Akathisia Rating (ARS) scales were administered. Higher FK506 plasma levels correlated with higher HAM-A scores. ARS scores did not correlate with FK506 plasma levels; however, when FK506 plasma levels were divided into "high" (> or = 0.9 ng/mL) and "low" (< 0.9 ng/mL) groups, total ARS and HAM-A scores were significantly higher in the "high" group. We discuss implications of these findings as well as management.

Adult↗

PubMed1996

Prevalence and predictors of depression and anxiety-related disorders during the year after heart transplantation.

This study longitudinally evaluates prevalence, clinical characteristics, and risk factors for DSM-III-R Major Depression, Generalized Anxiety Disorder (GAD), associated Adjustment Disorders, and Post-Traumatic Stress Disorder related to the transplant (PTSD-T) in a large, representative sample of heart recipients followed during the first year after transplantation. Lifetime pretransplant prevalence as well as 1-year posttransplant rates were determined for the 154 recipients via standardized clinical interview schedules. Major Depression was the most prevalent disorder posttransplant (1- year rate of 17.3%), followed by PTSD-T (13.7%), and Adjustment Disorders (10.0%). There were no cases of GAD. Specific pretransplant and perioperative factors increased recipients' risk for any psychiatric disorder (vs none) posttransplant, including pretransplant psychiatric history; poor social supports from primary family caregiver, other relatives, and friends; the use of avoidance coping strategies for managing health problems; and low self-esteem early posttransplant. Within diagnostic groups, additional risk factors distinguished recipients with anxiety-related vs depressive disorders posttransplant: those at highest relative risk for anxiety had waited more briefly for a donor heart, were more likely to have a family psychiatric history, had the poorest family and friend support of all recipients, utilized the poorest coping skills, and had a poor sense of mastery. The findings have implications for the development of primary and secondary prevention strategies for psychiatric disorder in heart recipient populations.

Adaptation, Psychological↗

PubMed1996

Assessment and follow-up of alcohol-dependent liver transplantation patients. A clinical cohort.

We describe pretransplantation characteristics of 103 consecutive alcoholic cirrhotics who underwent orthotopic liver transplantation over a 28-month period, and follow-up characteristics for 58 of 82 survivors. We examined whether certain pretransplantation psychiatric and demographic variables predicted posttransplantation outcomes. Patients who were sober < or = 6 months and those who died after transplantation had longer transplant hospital stays, suggesting that physiological compromise may predict posttransplant course. Using survival analyses because of variable follow-up intervals, only age over 50 years and index hospital stays greater than 1 month showed statistical trends toward predicting shorter posttransplant survival duration. Neither pretransplant sobriety, gender, nor duration of pretransplant heavy drinking predicted posttransplant survival duration. No variable, including preoperative sobriety < or = 6 months or attendance at alcohol rehabilitation peritransplant, predicted relapse except for female gender and pretransplant unemployment, in which cases the relapse rate was doubled. Our relapse rate of 21% is comparable to recidivism rates reported from other centers and for the general alcoholic population. These findings, several of which are contrary to general beliefs, continue to challenge our presumed predictive variables in selecting the best candidates for liver transplantation.

Adult↗

PubMed1996

Delirium. Advances in diagnosis, pathophysiology, and treatment.

This article discusses research in the areas of morbidity and mortality, epidemiologic risk factors, phenomenology, pathophysiology, and treatment of delirium. Delirium assessment instruments are reviewed. The neuropathophysiologic understanding of delirium is discussed in the context of important CNS neural circuitry. Pharmacologic treatments of delirium in adults and children are outlined, with particular emphasis on intravenous use of butyrophenone neuroleptics.

Adult↗

PubMed1995

Further analyses of the Delirium Rating Scale.

The Delirium Rating Scale is a clinician-rated, 10-item symptom rating scale for assessment of delirium severity. In order to better understand the relationship between items of the scale and whether they reflect one or more underlying groupings or dimensions, further analyses of the originally published scale data were performed. Factor analysis revealed a strong single underlying dimension that could be further divided into two components: one comprising delusions, psychomotor behavior, cognition, sleep-wake cycle disturbance, and mood lability; the other comprising temporal onset of symptoms, perceptual disturbances, hallucinations, and fluctuation of symptoms. Implications for improved phenomenological understanding of delirium are discussed.

Adult↗

PubMed1994

A review of delirium assessment instruments.

This paper reviews various types of assessment instruments for delirium, including nursing screening scales, symptom checklists, an analog scale, an interview schedule, and symptom rating scales. Their structures and applicability to the clinical and research assessment of delirium are described. Despite the seeming plethora of assessment methods, only a few are suitable for use by researchers.

Delirium↗

PubMed1994

SPECT scan and cognitive findings in subclinical hepatic encephalopathy.

The authors studied 6 patients with end-stage cirrhosis and 6 age- and sex-matched normal control subjects by using SPECT brain scans to determine whether subclinical hepatic encephalopathy (HE) altered regional cerebral blood flow (rCBF). In addition, cirrhosis patients performed a battery of standardized neuropsychological tests known to be sensitive to effects of liver disease, and these were compared with published norms. Results of cognitive tests that showed impairment were correlated with ratios of rCBF values. In cirrhosis patients, rCBF was decreased in bilateral frontotemporal and right basal ganglia regions as compared with control subjects. These defects were compatible with the cirrhosis patients' visuopractic neuropsychological deficits, which were consistent with known subclinical HE cognitive patterns.

Basal Ganglia↗

PubMed1994

Rat model of delirium: atropine dose-response relationships.

The authors report dose-response relationships for atropine in their rat model of human delirium. In this model, anticholinergic mechanisms are an important cause and may be a neurochemical final common pathway for diverse etiologies of delirium. Four intravenous (i.v.) bolus doses of atropine (27.5, 13.5, 6.875, and 3.44 mg/kg) were studied along with the originally reported dose of 55 mg/kg and saline control. Subsequent iv infusions were also proportionately reduced. EEG frequency and amplitude, maze performance, and subjective behavioral descriptions were taken over 320-minute study periods. Repeated-measures analysis of variance compared data between groups, and effect sizes were calculated. Dosages to be used in future studies are discussed.

Animals↗

PubMed1993

Etomidate anesthesia increases seizure duration during ECT. A retrospective study.

We reviewed charts of 28 consecutive depressed psychiatric inpatients who had received electroconvulsive therapy (ECT). As a preliminary investigation, we compared the effects of thiopental and etomidate anesthesia on seizure duration. Etomidate, a nonbarbiturate, has been shown to enhance seizure activity in other contexts. The mean age of our sample was 64 years. Because each patient received both etomidate and thiopental at various sessions during their course of ECT, each patient served as his or her own control. The mean proportion of etomidate sessions per patient was 54%. Mean seizure durations were significantly longer (p < 0.001) for the etomidate sessions as compared with the thiopental sessions. In contrast to some prior reports we found that the use of etomidate anesthesia in our sample of 28 consecutive inpatients enhanced seizure duration in ECT. Although controversial, some have advocated that longer seizure times will enhance effectiveness of ECT. We could not compare the anesthetic agents' clinical efficacy in relieving depression due to the retrospective nature of our study.

Adult↗