Terry Stedman

Energy expenditure and physical activity in clozapine use: implications for weight management.

Objective: The management of atypical antipsychotic-induced weight gain is a significant challenge for people with mental illness. Fundamental research into energy metabolism in people taking atypical antipsychotic medication has been neglected. The current study of men with schizophrenia taking clozapine aimed to measure total energy expenditure (TEE) and energy expended on physical activity – activity energy expenditure (AEE) and to consider the clinical implications of the findings. Method: The well-established reference method of doubly labelled water (DLW) was used to measure TEE and AEE in men with schizophrenia who had been taking clozapine for more than 6 months. Resting energy expenditure was determined using indirect calorimetry. Results: The TEE was 2511 ± 606 kcal day−1 which was signifcantly different to World Health Organization recommendations (more than 20% lower). The Physical activity level (PAL) was 1.39 ± 0.27 confirming the sedentary nature of people with schizophrenia who take clozapine. Conclusions: The findings support the need for weight management strategies for people with schizophrenia who take clozapine to focus on the enhancement of energy expenditure by increasing physical activity and reducing inactivity or sedentary behaviours, rather than relying primarily on strategies to reduce energy intake.

Quantitative analysis of two pyridinium metabolites of haloperidol in patients with schizophrenia

A pyridinium metabolite (HPP+) of the neuroleptic drug haloperidol has been identified in rats and in the urine of patients. The purpose of this study was to measure the steady‐state blood and plasma concentrations and daily urinary excretion of HPP+ in patients treated with haloperidol.

Two pyridinium metabolites of haloperidol are present in the brain of patients at post-mortem

We have shown in patients taking the antipsychotic drug haloperidol (HP) that two pyridinium metabolites (HPP+ and RHPP+) are present in blood and urine in nM concentrations. These metabolites are structurally analogous to MPP+, the neurotoxic metabolite of the well-known parkinsonian-producing protoxin, MPTP. In this study we measured the concentrations of HPP+ and RHPP+ in seven regions of the brain (putamen, substantia nigra, globus pallidus, caudate, hippocampus, cerebellum and occipital cortex) obtained at post-mortem from three patients who were taking HP before death. Blood, urine, and bile from one patient were analysed as well. HPP+ was present in all regions (except for substantia nigra in one patient and globus pallidus in another); the amount/g ranged from 1.6-8.3 pMol but there was no preferential sequestration of the metabolite in dopaminergic regions. Similarly, RHPP+ was present relatively uniformly in all regions; the amount/g ranged from 1.1-7.6 pMol. The concentrations of HPP+ and RHPP+ in one patient were 24 and 13 nM in blood, 660 and 230 nM in urine, and 13.0 and 1.4 microM in bile, respectively. The presence of these pyridinums in brain adds another important piece of information to the case that, at least for HP, metabolite-induced neurotoxicity could contribute to the extrapyramidal side-effects in patients receiving long-term therapy.

Monitoring consumer satisfaction with inpatient service delivery: the Inpatient Evaluation of Service Questionnaire.

Objective: To report on the development, testing and psychometric properties of a brief consumer satisfaction measure for use with psychiatric inpatients. Method: Focus group discussions with inpatients were used to develop a pool of items related to satisfaction with hospital stay. A second cohort of 72 inpatients was invited to rate the 51 items that emerged for importance in contributing to satisfaction. Mean importance scores highlighted 20 items that were subsequently framed into neutrally worded statements. A draft questionnaire comprising these statements was introduced, on a trial basis, in a range of inpatient facilities. Results: Factor analysis of 356 completed questionnaires yielded three factors comprising a staff-patient alliance; doctor/treatment issues; and an environmental component. Psychometric properties include good response variability and high internal consistency. Conclusions: The Inpatient Evaluation of Service Questionnaire addresses many of the shortcomings of existing satisfaction measures. It was developed through extensive consumer involvement, it is simply worded, easy to score and appears to perform well with acute and rehabilitation inpatients.

The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia

A double‐blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150–600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM‐III‐R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects.

Effects of nifedipine on psychosis and tardive dyskinesia in schizophrenic patients

In an open label study, two fixed doses of nifedipine (30 mg and 60 mg daily) were added to the usual antipsychotic drug treatments of 10 patients suffering from chronic schizophrenia. While no patient experienced significant improvements, statistically significant falls in Brief Psychiatric Rating Scales scores were observed. A significant reduction in Abnormal Involuntary Movement Scale scores was observed in those patients with tardive dyskinesia. After the addition of nifedipine, four of the 10 patients showed large increases in plasma neuroleptic activity (radioreceptor assay) that decreased to baseline levels within two weeks. The possibility that this represents competitive inhibition and subsequent induction of the liver metabolism of the antipsychotic drugs is discussed. Adverse effects encountered are also discussed.

A gap approach to exploring quality of life in mental health.

Improving quality of life (QoL) is an important treatment outcome for the serious mentally ill. There is, however, a need for an instrument which both captures consumers own assessments and gives direct information for intervention. A useful approach is to define QoL as the gap between actual and ideal life circumstances, which is weighted by importance. In this paper we detail how we developed and evaluated a QoL instrument which follows this model. This instrument, the (QoL-GAP), is based on self-appraised items within various life domains. For each item respondents firstly identify what they have (actual) and then what they would like (ideal). They then rate the item for its importance and make any comments. A weighted gap score for each item is subsequently derived from the ideal–actual gap being weighted by the importance rating. This weighted gap score is then related to domain satisfaction ratings, while their average from each domain is related to overall satisfaction and well-being. We surveyed 120 individuals with a serious and enduring mental illness living in different types of residences, such as psychiatric hospitals, hostels, or their own homes, in a largely urban part of Queensland. Sixty-eight percent were males, and 92% had schizophrenia or related disorders. We found that our approach demonstrated good psychometric properties, and that the model-based predictions were borne out: weighted gap measures were consistently more strongly related to domain satisfaction than were the actual circumstances alone. While further work is being undertaken – in such matters as short-forms and further evaluation of the QoL-GAP in a longitudinal study – our results suggest that this (gap) approach helps consumers state their own goals and give their opinions – and so is particularly relevant for consumer-focused mental health delivery and research.

Does Supported Accommodation Improve the Clinical and Social Outcomes for People with Severe Psychiatric Disability? The Project 300 Experience

Objective: The present study was designed to investigate the clinical and social outcomes for a group of individuals (n = 181) discharged into supported accommodation from three long-stay facilities in Queensland. Method: Data were collected prospectively using a battery of standardized measures and individual interviews at 6 weeks pre-discharge and again at 6, 18, 36, and 84 months post-discharge. Results: While there was little functional gain at follow up, the clients, as a group, did not deteriorate. Sixty per cent of the clients were engaged in some form of structured community activity and the need for hospitalization decreased significantly in the follow-up period. The ongoing costs of the programme, while remaining high, were significantly less than inpatient alternatives. Conclusion: The provision of community accommodation with adequate clinical and non-clinical support is a suitable option for a large proportion of individuals with serious mental illness.

Approaches to Measuring Quality of Life and their Relevance to Mental Health

Objectives: This paper describes the ‘sociological’ and ‘health-related’ approaches to the measurement of quality of life and aims to describe their major findings, shortcomings and potential uses with mental health problems. Method: The literature is selectively reviewed to illustrate the major developments and conclusions. Results: Despite the lack of an accepted definition of quality of life, sociological approaches have repeatedly shown in general populations, the mentally ill and the elderly that subjective assessments are more influential in determining expressions of happiness, wellbeing and life satisfaction than are the objective circumstances of a persons life. This supports the use of subjective judgements as the basis for quality-of-life determinations. Conclusions: The quality-of-life approaches can help to answer a broad range of questions of interest to psychiatry. Health-related quality-of-life approaches are potentially useful methods of demonstrating the impact of mental illness and the benefit of interventions. Further work is required to determine whether the commonly used measures are sensitive to change.

Determination of haloperidol and reduced haloperidol in the plasma and blood of patients on depot haloperidol

We developed a sensitive HPLC assay to measure haloperidol (HA) and its metabolite, reduced haloperidol (RH), in plasma and whole blood. The conditions under which HA might be converted to RH during collection and analysis of blood were examined. Provided the blood was kept at 0° C, erythrocyte ketone reductase activity was insignificant. The solid phase extraction method did not generate RH. We studied ten patients taking 25–400 mg/month of HA decanoate and one patient for 4 weeks after the daily oral dose of 120 mg HA was ceased. In the patients on depot HA, the plasma and blood concentrations of HA were not significantly different (P>0.1). For the first time, RH was detected in plasma patients on depot drug, but only in three cases. In contrast, RH was present in the blood of eight of these patients. The accumulation of RH in red blood cells was also evident in the patient on oral HA, in whom the mean ratio of RH concentrations in whole blood to plasma was 3.6±1.1. Plasma concentrations of HA correlated highly with total neuroleptic activity measured by a radioreceptor assay. Compared to plasma, analysis of concentrations of HA and RH in blood has the advantages of greater sensitivity, of using smaller volumes of blood and of avoiding the efflux of HA and RH during separation of plasma and red cells.