Psychopharmacologic issues in organ transplantation. Part I: Pharmacokinetics in organ failure and psychiatric aspects of immunosuppressants and anti-infectious agents.

This article discusses pharmacokinetics and pharmacodynamics during hepatic, renal, and cardiovascular insufficiencies. Hepatic metabolism of psychotropic drugs and of drugs commonly used in transplant patients that have neuropsychiatric side effects is discussed. Neuropsychiatric effects of immunosuppressant agents, including cyclosporine, corticosteroids, azathioprine, OKT3, and FK 506, are reviewed. Certain infections occur more often in immunosuppressed patients; their treatment with antiviral, antifungal, and antibiotic drugs may have neuropsychiatric consequences. Because of altered drug sensitivities and metabolism, drug interactions, and severe medical illness, most drugs are used in reduced doses.

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.

The relationship of SPECT scans to behavioral dysfunction in neuropsychiatric patients.

The authors describe 20 neuropsychiatric inpatients consecutively evaluated in the context of routine clinical care. Patients had both a neurological and psychiatric disorder. Each was clinically evaluated as part of a psychiatric hospitalization. DSM-III-R diagnoses, electroencephalograms, magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain, single photon emission computed tomography (SPECT) scans of the brain, and cognitive testing are reported. In only three cases were SPECT, MRI (or CT), and electroencephalogram all normal. SPECT abnormalities were associated with behavioral and cognitive presentations and with the hypothesized anatomical areas of dysfunction in 16 cases. In six cases SPECT and MRI were equivalent, involving structural lesions or normal scans. In only one case did MRI (or CT) detect deficits not revealed by SPECT, which were nonspecific white matter lesions and atrophy. The authors conclude that SPECT scans may be superior to structural brain scans in detecting clinically relevant deficits in neuropsychiatric patients, particularly when physiological lesions are involved.

An animal model for delirium.

This study describes an animal model for delirium comparing rats treated with either saline or atropine. The model was defined by recordings of cortical EEGs, maze performance, and behavioral observations. EEG slowing and increased amplitude, difficulty with attention and memory, sleep-wake cycle reversal, and changes in behavior (lack of focused direction, irritability, fluctuating levels of activity, excessive random sniffing) appeared consistent with signs and symptoms seen in human delirium. EEG abnormalities in atropine-treated rats returned to normal before cognitive deficits did. Motor activity monitoring did not reveal diminished motor activity as a confounding variable in maze performance.

Delirium in liver transplantation candidates: discriminant analysis of multiple test variables.

We report the results of electroencephalograms, Mini-Mental State exam, Trailmaking Tests A and B, and serum albumin levels in 108 consecutive liver transplantation candidates. We compared test results to a clinical DSM-III diagnosis of delirium. Although each variable could differentiate between the two groups (delirium n = 18; nondelirium n = 90) at a statistically significant level, a discriminant analysis involving either all variables or only three particular variables (Trailmaking B, EEG code, and albumin) resulted in the highest specificity (97.8%) and sensitivity (83.3%), with a correct classification of 95.4% of subjects. The analysis also generates an equation that can be applied to clinical situations to enhance the accurate recognition of delirium. In addition, to explain abnormal Trailmaking B scores and/or EEGs in subjects who did not otherwise meet DSM-III criteria for delirium, we suggest the presence of a "subclinical delirium."

Psychiatric and neuropsychological response to propranolol in Graves' disease.

We describe the endocrine, psychiatric, and neuropsychological assessments of 10 untreated, newly diagnosed Graves' disease subjects who were studied longitudinally at three stages: hyperthyroid (stage 1), after 2 weeks of propranolol treatment (stage 2), and after 6 months of antithyroid treatment (stage 3). Major depression, generalized anxiety disorder, and hypomania were diagnosed at stage 1. Elevations on psychiatric symptom rating scales and in motor activity monitoring at stage 1 were significantly decreased at stage 2 and again at stage 3. Psychiatric improvements paralleled improvements in endocrine symptoms. Neuropsychological improvements were noted on the more challenging memory and attention tasks at stage 3, whereas propranolol treatment was not associated with changes on attention tests. Results are discussed in relation to catecholamine-thyroid hormone interactions, in particular, the beta-adrenergic system.

A symptom rating scale for delirium.

The authors present a 10-item clinician-rated symptom rating scale for delirium. Compared to demented, schizophrenic, and normal control groups, 20 delirious subjects scored significantly higher on the scale, which quantitates multiple parameters affected by delirium. The scale can be used alone or in conjunction with an electroencephalogram and bedside cognitive tests to assess the delirious subject.