A survey of the use of community treatment orders by psychiatrists in Saskatchewan.

OBJECTIVE: To determine the pattern of use and satisfaction with community treatment orders (CTOs) by psychiatrists in Saskatchewan. METHOD: All psychiatrists who were licensed to practise by the College of Physicians and Surgeons of Saskatchewan were surveyed by mail in July 1998. RESULTS: The response rate was 72%. The responding psychiatrists were treating 14 patients on CTOs at the time of the survey. Psychiatrists were generally satisfied with the operation of CTOs, though many felt that commitment of only of 3 months before mandatory renewal was too short a period. Almost one-half expected their use of treatment orders to increase. CONCLUSION: While CTOs are used for only a small number of patients in Saskatchewan, they are a clinically useful tool for dealing with a group of otherwise difficult-to-treat patients.

Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor.

Neuroanatomical studies of schizophrenia suggest that progressive neuropathological changes (such as neuronal atrophy and/or cell death) occur over the lifetime course of the disease. Early intervention with atypical neuroleptics has been shown to prevent progression of at least some symptoms, although the mechanisms by which neuroleptics may do this remain unknown. In this study, PC12 cells were used to determine the effects of the new atypical antipsychotic olanzapine on the gene expression of superoxide dismutase (SOD1) and the low affinity nerve growth factor receptor (p75). The results show that olanzapine increases SOD1 at concentrations of 10 and 100 microM after 48 hr of incubation in PC12 cultures. The treatment decreases p75 gene expression at concentrations 100 microM after 48 hr of incubation. Since both the upregulation of SOD1 mRNA and the antisense blockade of p75 mRNA have been associated with reduced cell death, our results suggest that olanzapine has neuroprotective potential and thus may be useful in preventing further neurodegeneration accompanying schizophrenia.

Verbal learning by major depressive disorder patients during treatment with fluoxetine or amitriptyline.

After 1 week of a single-blind placebo period, and prior to being randomly assigned to receive treatment with either fluoxetine or amitriptyline, patients meeting strict criteria for a diagnosis of major depressive disorder were given an auditory verbal learning test of working memory, and a blood sample was drawn. After 3 weeks of drug treatment with either amitriptyline or fluoxetine, the patients' symptoms were evaluated, the verbal learning test was repeated, and a second blood sample was taken. The clinical evaluation, the verbal learning test and the blood drawing were repeated a third time 3 weeks after the second assessment. The amount of anticholinergic activity in the blood samples was measured by a competitive radioligand binding assay and expressed in atropine equivalents. Analyses of variance indicated that there were no significant differences at the predrug Assessment 1 between patients subsequently assigned to the fluoxetine group compared with those assigned to the amitriptyline group. At Assessments 2 and 3, the fluoxetine and the amitriptyline groups showed equal clinical improvement but patients receiving amitriptyline did not perform as well on the verbal learning task. Serum anticholinergic activity at Assessments 2 and 3 was considerably higher in the amitriptyline group. This supports the hypothesis that blockade of muscarinic receptors impairs working memory formation. Equally effective antidepressant drugs with little or no anticholinergic action, such as fluoxetine, may be preferable in patients with pre-existing mild cognitive impairment or in patients where a slight reduction in cognitive performance is not acceptable.

Longitudinal effect of amitriptyline and fluoxetine treatment on plasma phenylacetic acid concentrations in depression.

Unconjugated (U-PAA), conjugated (C-PAA), and total phenylacetic acid (T-PAA) concentrations in blood plasma and monoamine oxidase (MAO) activity in platelets towards phenylethylamine (PE) were determined in 40 drug-free, depressed patients (23 melancholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all depressed patients or between melancholic and nonmelancholic depressed patients. Treatment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentrations. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment times, however, plasma PAA concentrations and psychiatric rating scores were not significantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores.

Deuterium-labelled p-tyramine challenge test and phenolsulfotransferase activity in depressed patients--failure to replicate decreased p-tyramine conjugation in depression.

1. Depressed and normal subjects were challenged with deuterium-labelled p-tyramine and urine was collected for 3 h. 2. Urinary excretion of conjugated p-tyramine was not significantly different between normal, melancholic and non-melancholic depressed subjects. 3. Platelet phenolsulfotransferase activity to p-tyramine (p less than 0.05) and to phenol (p less than 0.005) were significantly lower in the depressed patients.

Defining treatment refractoriness in schizophrenia.

Addressing the need for research on the nature of refractoriness to antipsychotic drug therapy exhibited by a substantial minority of schizophrenic patients, Philip R.A. May and Sven Jonas Dencker instigated an international study group to discuss this problem, beginning with the International Congress of Neuropsychopharmacology in Göteborg, Sweden, in 1980. The study group subsequently met in Haar, Federal Republic of Germany, in 1985; in Banff, Canada, in 1986; and again in Telfs, Austria, in 1988. The study group set three objectives: (1) to clarify the concept of treatment resistance or refractoriness; (2) to suggest criteria for defining or rating the degree of treatment refractoriness; and (3) to explore the role of psychosocial and drug therapies in increasing the responsiveness of the treatment refractory patient. This position article represents a distillation of the study group's efforts to define treatment refractoriness in schizophrenia.

General management issues in depressive illness--family interventions.

There is a need to integrate interpersonal, spousal and family interventions into the well developed pharmacological and individual psychological therapies for depressive illness. Serious repercussions from depressive illness for the person themselves and their families, are well recognized. These include a low entrance rate to treatment programs, attrition from and poor adherence to, recognized therapies, self-harm, marital separation and divorce, family disruption and serious negative impacts on their children. A number of specific interventions, have been developed some psychoeducational, some therapeutic, and they appear to offer promise for future application. These need to be regularly applied to treatment situations in a planned fashion, and their effectiveness rigorously evaluated.

Intersubject variation in the pharmacokinetics of haloperidol and reduced haloperidol.

Single oral doses (5 mg) of haloperidol were administered to 36 healthy men (26 black, 10 white) of whom 28 (22 black, 6 white) completed the study. Plasma samples harvested over 96 hours were analyzed for haloperidol and reduced haloperidol by means of a new high performance liquid chromatographic method. Reduced haloperidol was detectable in the plasma of only six of the 28 subjects (five blacks, one white). In these individuals reduced haloperidol plasma concentrations were generally much lower than those of the parent drug. This finding in the present single-dose study is in contrast to literature reports that have described levels of reduced haloperidol higher than those of the parent drug in some patients chronically mediated with haloperidol. There was wide intersubject variation in area under the plasma concentration versus time curve and apparent oral clearance values for haloperidol. The distributions of these pharmacokinetic parameters about their respective means were each leptokurtotic and skewed toward higher values. In each case the geometric mean gave a better estimate of central tendency than the arithmetic mean. Wide intersubject variation prevented the detection of significant differences in these pharmacokinetic parameters between black and white subjects or between smokers and nonsmokers.

Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients.

Low-dose scopolamine, given as presurgery medication, resulted in low levels of serum anticholinergic activity and caused measurable cognitive impairment in 18 psychiatrically healthy elderly patients. The degree of impairment was directly related to serum anticholinergic activity levels and, in the small subgroup of patients scheduled for spinal anesthesia, to CSF anticholinergic activity. Two of the mental status tests used, the Rey Auditory-Verbal Learning Test and the Saskatoon Delirium Checklist, were sensitive enough to detect these mild drug-induced changes, while two other tests, the Mini-Mental State and the Symbol Digit Modalities Test, were not.

Conversion mutism: case report and discussion.

Conversion mutism is an uncommon disorder that was in the past most frequently reported during wartime. Other than during wartime, young women are the most commonly affected and usually present shortly after a traumatic event. Both psychodynamic and behavioral elements are important etiologically and, thus the treatment should include both psychodynamic and behavioral methods. The patient described in this paper had underlying fears relating to sexual assault as well as behaviorally reinforced perpetuation of her symptom. She regained her speech after four weeks of combined psychodynamic and behavioral therapy.

Mental dysfunction and the blockade of muscarinic receptors in the brains of the normal elderly.

Cholinergic neurons innervate many areas of the brain and the disruption of acetylcholine neurotransmission at the muscarinic receptors in these areas produces dysfunction in a wide variety of mental, emotional and physiological activities. A side effect of many psychoactive drugs is the blockade of muscarinic receptors and this can result in a marked reduction of acetylcholine neural function particularly in elderly patients receiving 2 or more such drugs, and mimic the mental impairments seen in Alzheimer's Disease. A battery of mental status and short term memory tests was given the day before and 45 minutes after the administration of 0.005 mg/kg scopolamine or saline as presurgery medication to 30 normal patients over 60 years of age scheduled for lower body surgery. Total antimuscarinic activity was determined using a competitive binding assay in a 10 ml sample of blood taken from all patients after the pretest and again at the time of surgery, and in a 2 ml sample of cerebral spinal fluid taken from patients receiving spinal anesthesia immediately prior to administering the anaesthetic. The very low dose of scopolamine given to these patients produced antimuscarinic activity equivalent to 100 pmoles atropine in serum and 74 pmoles atropine in CSF. This resulted in a significant impairment of short term memory but had no significant effect on global scores on the Mini Mental State nor on the Delirium Check List.

Types of depression in alcoholic patients.

Standardized clinical interviews of 48 alcoholic patients consecutively admitted to an alcoholism treatment program revealed that 22 (46%) had suffered major depressive episodes. However, only two had the typical depressed affect at the time of the interview. Cyclic mood swings, panic attacks and hypomania were common, indicating that this was a heterogeneous group of depressed patients. The alcoholism tended to precede the onset of depression, which was then followed by the seeking of help, but the whole sequence developed over a few years, when the patients were in their early 20s. The depressed patients had more psychiatric, marital and legal difficulties than the nondepressed patients. There is a need for better definitions of affective disorders in alcoholic patients.

Epinephrine and norepinephrine responses in continuously collected human plasma to a series of stressors.

The present study employed continuous blood withdrawal to examine epinephrine and norepinephrine responses to a cognitive stressor (mental arithmetic), active physical stressors (handgrip and knee bends), passive painful stressors (venipuncture and cold pressor), and a medical procedure that was considered nonstressful (blood pressure measurements). The data were analyzed by analysis of variance (ANOVA) and by time series analysis. The ANOVA indicated that epinephrine and norepinephrine increased significantly in response to the stressors. Epinephrine showed a greater increase to the cognitive stressor than to the others. Time series analysis, however, showed a more varied pattern. It indicated that the height and duration of response differed considerably across subjects and across interventions. The results from both analytic procedures are compared and discussed in terms of current hypotheses of catecholamine response.

A possible neurochemical basis for the neuropsychiatric aspects of baclofen therapy.

Baclofen, commonly used to reduce severe muscle spasms in patients with spinal cord injuries, is also active in the brain. A patient with pre-existing bipolar affective disorder developed increased depression while on baclofen, which progressed to a delusional depression when baclofen and haloperidol were rapidly decreased. When the dose of haloperidol was increased to a previously well tolerated dose to deal with the depressive delusion, a pseudoparkinson's state developed. This case demonstrates the interactive effects of baclofen and haloperidol on central noradrenergic and dopaminergic systems and suggests a possible neurochemical basis for the difference between delusional and nondelusional depression that is consistent with the different therapeutic response to psychotropic drugs of patients with these illnesses. The paradoxical appearance of the pseudoparkinson state in this patient when much higher doses of haloperidol had been free of such side effects, may reflect baclofen-induced alterations in receptor sensitivity. It appears that baclofen should be used with caution in patients with neuropsychiatric problems and that, when used, the withdrawal of baclofen should be continued over several weeks to allow receptor sensitivity to return to normal levels.