Use of psychiatric emergency services and enrollment status in a public managed mental health care plan.

OBJECTIVE: This study examined the sociodemographic and clinical characteristics of acute-care psychiatric patients who visited the emergency department at a large public hospital in terms of the patients' enrollment status in the region's public managed mental health care plan. The results of the analyses were expected to provide information about the degree and types of access to care for individuals who are and are not enrolled in the plan. METHODS: Data were collected over a seven-month period for 2,419 patients who visited a large, inner-city crisis triage unit. Patients were grouped according to whether they were currently enrolled, previously enrolled, or never enrolled in the public managed mental health care plan. Univariate and logistic regression models were used to determine differences between the three groups. RESULTS: In general, patients who were currently enrolled in the plan had a higher rate of functional psychosis, past use of psychiatric services, and functional disability and lower rates of substance use and homelessness. Previously enrolled patients had a more moderate rate of psychosis but a higher rate of substance use, functional disability, and homelessness. The never-enrolled patients had a lower rate of psychosis, functional disability, and past use of psychiatric services, and moderate substance use. CONCLUSIONS: The region's public health plan appeared to be succeeding in engaging and keeping the most psychiatrically impaired patients in treatment; however, individuals with moderate psychiatric symptoms and high levels of substance abuse may never have been enrolled in the plan because of Medicaid ineligibility or because they dropped out of treatment. Problematic behavior and history of hospitalization were the best predictors of enrollment status.

Shorter hospital stays and more rapid improvement among patients with schizophrenia and substance disorders.

OBJECTIVE: Length of stay and treatment response of inpatients with acute schizophrenia were examined to determine whether differences existed between those with and without comorbid substance-related problems. METHODS: The sample comprised 608 patients with a diagnosis of schizophrenia or schizoaffective disorder treated on hospital units with integrated dual diagnosis treatment. They were rated on admission and discharge by a psychiatrist using a structured clinical instrument. Patients with no substance-related problems were compared with those with moderate to severe problems using t tests, chi square tests, and analysis of variance. RESULTS: When analyses controlled for age, gender, and other clinical variables, dually diagnosed patients were found to have improved markedly faster compared with patients without a dual diagnosis. Their hospital stays were 30 percent shorter on both voluntary and involuntary units. They also showed somewhat greater symptomatic improvement and no increase in 18-month readmission rates. On admission the dual diagnosis group was more likely to be younger, male, and homeless and more likely to be a danger to self and others. Severity of psychosis was the same at admission for the two groups, but the dually diagnosed patients were rated as less psychotic at discharge. CONCLUSIONS: Dually diagnosed patients with schizophrenia appear to stabilize faster during acute hospitalization than those without a dual diagnosis. The authors hypothesize that substance abuse may temporarily amplify symptoms or that these patients may have a higher prevalence of better-prognosis schizophrenia. The availability of integrated dual-focus inpatient treatment and a well-developed outpatient system may also have helped these patients recover more rapidly.

Assertive Community Treatment for patients with chronic and severe mental illness who abuse drugs.

The Assertive Community Treatment model of mental health service delivery has been extensively studied and has undergone various modifications over the past twenty years. This article describes a modified ACT Team approach to the treatment of individuals who suffer from severe comorbid mental illness and substance abuse. Demographics of patients who are chosen to receive these intensive services, service utilization patterns, and elements of team treatment are discussed. Comparisons with less severely ill dual diagnosis patients who receive more traditional case management services are reviewed.

Predictors and outcome of discharge against medical advice from the psychiatric units of a general hospital.

OBJECTIVE: The study examined predictors of discharge against medical advice (AMA) and outcomes of psychiatric patients with AMA discharges, as measured by poorer symptom ratings at discharge and higher rates of rehospitalization. METHODS: A total of 195 patients discharged AMA from general hospital psychiatric units were compared retrospectively with 2,230 regularly discharged patients. AMA status was defined as signing out against medical advice, being absent without leave, or being administratively discharged. All patients received standardized assessments within 24 hours of admission and at discharge. Demographic characteristics, psychiatric history, DSA-IV psychiatric and substance use diagnoses, and scores on an expanded 32-item version of the Psychiatric Symptom Assessment Scale were compared. RESULTS: The groups did not differ in primary psychiatric diagnoses. Patients discharged AMA were significantly less likely to be Caucasian or to be functionally impaired due to physical illness. They were more likely to live alone, have a substance use diagnosis, use more psychoactive substances, and have more previous hospitalizations. Patients discharged AMA had significantly shorter lengths of stay, higher rehospitalization rates, and more severe symptoms at discharge, even when length of stay was taken into account. The differences between the groups in male gender and young age were better accounted for by a greater likelihood of substance abuse in these groups. CONCLUSIONS: The results suggest a profile of patients who may be discharged AMA. Such patients have worse outcomes and are more likely to be high utilizers of inpatient resources. Aggressive identification of patients likely to be discharged AMA and early discharge planning for appropriate outpatient treatment are recommended.

The MOS 36-Item Short Form Health Survey: reliability, validity, and preliminary findings in schizophrenic outpatients.

OBJECTIVES: The authors test the reliability and validity of the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) as a written, self-administered survey in outpatients with chronic schizophrenia. METHODS: Thirty-six schizophrenic outpatients completed a written and oral form of the SF-36. A psychiatrist rated the patients using the Brief Psychiatric Rating Scale to determine severity of psychopathology. Cognitive functioning and academic achievement were also assessed. Internal consistency, test-retest reliability, concurrent and discriminative validity of the oral and written versions were determined. RESULTS: The SF-36 in both forms was shown to have good internal consistency, stability, and concurrent validity. The mental health SF-36 subscales had poor discriminant validity, compared with the physical functioning scale that demonstrated good discriminant validity. CONCLUSIONS: The validity of using the written form of the SF-36 on a sample of patients with chronic mental illness was demonstrated. The SF-36 appears to be an appropriate outcome measure for changes in physical and role functioning in consumers of outpatient mental health programs.

Relationships between neuropsychological and oculomotor measures in schizophrenia patients and normal controls.

Establishing the relationship between oculomotor and neuropsychological impairments might facilitate a more coherent description of schizophrenia-associated neurocognitive deficits. Therefore, we assessed several aspects of neuropsychological and oculomotor function in 25 medicated schizophrenia patients and 24 age-matched controls. Neuropsychological tasks included the Wisconsin Cart Sort Test (WCST), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test, and finger tapping speed. Oculomotor functions assessed included smooth pursuit, initiation of smooth pursuit, predictive pursuit, fixation, visually guided saccades, remembered saccades, and antisaccades. Among the schizophrenia patients, predictive pursuit performance correlated significantly with finger tapping (dominant hand), TMT (both parts), and one WCST measure (categories completed). The only other significant correlation among the schizophrenia patients was between antisaccade performance and part A of the TMT. Perseverative errors during the WCST and antisaccade performance were the only measures significantly correlated among the normals. Closely related neurocognitive deficits may be responsible for impairments in TMT, WCST, predictive pursuit, and antisaccade performance in schizophrenia.

Cardiovascular and catecholamine response to orthostasis in panic and obsessive-compulsive disorder and normal controls: effects of anxiety and novelty.

OBJECTIVE: Studies of the cardiovascular and catecholamine response to orthostatic challenge in panic disorder patients have yielded conflicting results. Failure to control for the effects of both anxiety and novelty, which contribute to subjects' response to orthostatic challenge in control patients, could possibly account for this. METHODS: The blood pressure, pulse, plasma norepinephrine and epinephrine responses to orthostasis were examined in patients with panic disorder, obsessive-compulsive disorder (to control for nonspecific anxiety effects), and controls, on two separate days a week apart (to control for novelty). RESULTS: All measures showed robust and significant increases with orthostatic challenge that were generally similar across groups. Pressure responses were greater on average on the first compared with the second day and panic disorder patients had higher plasma norepinephrine levels throughout the study and a diminished diastolic blood pressure response on the first day. CONCLUSIONS: These findings in general support the absence of consistent peripheral autonomic nervous system differences in response to orthostatic challenge in panic disorder patients.

Effect of benzodiazepines on plasma levels of homovanillic acid in anxious patients and control subjects.

The effects of four logarithmically increasing doses of intravenous diazepam or placebo on plasma homovanillic acid (HVA) were determined in benzodiazepine-naive patients with panic disorder (PD) or generalized anxiety disorder (GAD), and in healthy controls. Plasma HVA was measured at baseline and 3 min after the first and fourth doses of diazepam/placebo. Mean baseline plasma HVA levels were significantly lower in PD patients compared with GAD patients and controls. Although plasma HVA levels decreased significantly with time in all groups, there was no diazepam effect. This study suggests that low dopaminergic activity may occur in a subset of anxious patients (PD), and that diazepam does not significantly affect dopaminergic activity as measured by plasma HVA in humans.

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects.

OBJECTIVE: The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. METHOD: The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. RESULTS: Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. CONCLUSIONS: Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.

Hypothalamic-pituitary-adrenocortical axis responses to physostigmine: effects of Alzheimer's disease and gender.

We asked whether hypothalamic-pituitary-adrenocortical (HPA) axis responses to a cholinergic stimulus are blunted in patients with Alzheimer's disease (AD) of mild to moderate severity. Such a finding would be consistent with a central cholinergic deficiency early in the course of AD. To address this question, we measured the plasma adrenocorticotropic hormone (ACTH), beta-endorphin-like immunoreactivity (beta E-LI), and cortisol responses to the cholinesterase inhibitor physostigmine in 10 healthy normal older subjects (age = 71 +/- 2 years) and 11 outpatients with probable AD (age = 72 +/- 2 years; Mini Mental State Exam score = 19 +/- 2). Cortisol concentrations were higher in AD subjects throughout the study, but AD and normal older subjects had similar robust ACTH, beta E-LI, and cortisol responses to physostigmine. In all subjects combined, women had greater ACTH, beta E-LI, and cortisol responses to physostigmine than did men. Plasma physostigmine concentrations did not differ between groups. These results suggest that female gender enhances the magnitude of HPA axis responses to cholinergic stimulation in older humans; however, the HPA axis response to physostigmine does not appear to reflect central cholinergic deficiency in the early stages of AD.

Oral physostigmine in Alzheimer's disease: effects on norepinephrine and vasopressin in cerebrospinal fluid and plasma.

Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in persons with Alzheimer's disease (AD) the effects of an acute dose of physostigmine in patients receiving chronic physostigmine treatment on the activity of the cholinergically regulated noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated the effects of sustained release oral physostigmine on central and peripheral noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic saline infusion also were measured. NE concentrations in both CSF and plasma were significantly lower in the physostigmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affect the AVP response to hypertonic saline. Physostigmine appears to decrease both central and peripheral noradrenergic activity in AD.

Effects of Alzheimer's disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine.

BACKGROUND: The resting cerebrospinal fluid (CSF) norepinephrine concentration is unchanged or even increased in patients with Alzheimer's disease (AD). These in vivo findings appear to be inconsistent with the post-mortem locus ceruleus neuronal loss that is reported in patients with AD. METHODS: The effects of AD and advanced age on central nervous system noradrenergic status were estimated by comparing CSF norepinephrine concentrations following the administration of yohimbine hydrochloride, clonidine hydrochloride, and placebo in outpatients with AD and older and young normal subjects. Levels of yohimbine, its metabolite 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, Excitement, and Anxiety items on the Brief Psychiatric Rating Scale. RESULTS: Yohimbine-induced increases of CSF norepinephrine concentrations were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepinephrine concentrations did not differ among groups. Behavioral arousal following the administration of yohimbine was greater in patients with AD than in the other groups. CONCLUSIONS: Central nervous system noradrenergic responsiveness is enhanced in normal older subjects, and this age effect is retained in patients with AD. Behavioral sensitivity to increased central nervous system noradrenergic activity is enhanced in patients with AD.

Human oculomotor function: reliability and diurnal variation.

To provide information on test-retest reliability for seven oculomotor paradigms currently used in studies of schizophrenia and other neuropsychiatric conditions, we tested eight controls at four weekly intervals, twice in the morning (8-10 AM) and twice in the afternoon (3-5 PM). Intraclass correlation coefficients were significant (p < .05) for both AM and PM pairs of measures as well as for mean AM and PM pairs for closed-loop pursuit gain, open-loop pursuit gain (using velocity as the measure), saccadic frequency during pursuit and fixation, visually and nonvisually guided saccadic latency and velocity, antisaccadic latency, and premature reflexive saccades during the memory-guided saccade task. Acceleration as a measure of open-loop gain (for slower targets) and accuracy of saccades to a moving target were only reliable at PM testing time. Nonvisually guided saccadic accuracy and inappropriate reflexive saccades during the antisaccade task were not reliable, possibly due to the narrow range of values for these measures. Except for approximately 10% fewer saccades during pursuit and fixation in the morning, there were no consistent diurnal differences. These findings suggest that, in a small sample of subjects, most measures of oculomotor function are stable across time and may reflect underlying neurophysiologic traits.

Enhanced hypothalamic-pituitary-adrenocortical axis responses to physostigmine in normal aging.

BACKGROUND: The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physostigmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity. METHODS: Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10-minute infusion of physostigmine (.0125 mg/kg) were compared between groups of 10 normal older subjects (71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentrations were measured to assess the comparability of the pharmacologic stimulus between groups. RESULTS: Endocrine responses were substantially greater in older subjects than young subjects for ACTH (p < .01), beta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentrations did not differ between older and young subjects. CONCLUSION: This study demonstrated increased HPA axis responsivity to a CNS cholinergic stimulus in normal human aging.

Plasma arginine vasopressin response to hypertonic saline infusion in Alzheimer disease.

In this study, we tested the hypothesis that the plasma arginine vasopressin (AVP) response to osmotic stimulation induced by hypertonic saline infusion is blunted in the early and middle stages of Alzheimer disease (AD). Because animal data support stimulatory cholinergic mediation of AVP osmoregulation at a brain level, the AVP response in AD might provide clinically useful information about the status of brain cholinergic systems. Seventeen AD outpatients and eight normal older subjects underwent both a 90-min hypertonic saline infusion and a 90-min control (normal saline) infusion. Substantial increases in plasma osmolality during hypertonic saline infusion were accompanied by substantial and linear increases in plasma AVP in both groups. However, there were no significant differences in AVP responses between AD and normal older subjects. These results do not support the utility of plasma AVP response to hypertonic saline in the assessment of brain cholinergic status in AD.

Lack of cholinergic regulation of vasopressin and norepinephrine responses to hypertonic saline in humans.

In vitro studies in hypothalamic-pituitary explants in the rat have suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.

Psychopharmacologic treatment of panic, generalized anxiety disorder, and social phobia.

The anxiety disorders discussed in this article are common, affecting 5% to 10% of the general population. They may cause significant distress and disability and are often complicated by substance abuse and depression. Fortunately, these disorders can be treated successfully in the majority of patients, with alleviation of the most distressing symptoms and significant improvement in occupational and social functioning. Systematic research studies during the past decade have identified both specific medication-responsive anxiety syndromes and a variety of psychopharmacologic agents effective in their management. Psychopharmacologic treatment, often in combination with cognitive-behavioral therapies, can be tailored for the individual patient based on that patient's specific anxiety syndrome, comorbid disorders, and vulnerability to side effects. Careful monitoring of target symptoms can be used to assess the efficacy of treatment. Future research will help to develop new classes of antianxiety agents for currently treatment-resistant patients, and to investigate further the necessary duration of psychopharmacologic treatment.

Personality traits and early discontinuation from clinical trials in anxious patients.

Patients who discontinue early from clinical trials frequently give ambiguous or no reasons for leaving the study. Using Cloniger's Tridimensional Personality Questionnaire, we examined the potential role of personality traits in early discontinuation in patients with panic disorder and generalized anxiety disorder. Early dropouts and completers were comparable at baseline on demographic and clinical variables but differed significantly on the Tridimensional Personality Questionnaire. For panic disorder and generalized anxiety disorder patients combined, early dropouts scored higher on total novelty seeking, as well as on the novelty-seeking traits of both disorderliness/dislike of regimentation and impulsiveness. There was no significant interaction between dropout status and diagnosis for this finding, indicating it applied equally to both groups. This study suggests that personality traits involving novelty seeking may contribute to early discontinuation from clinical trials, independent of side effects, lack of efficacy, or at baseline, significantly worse symptoms of anxiety.