Competence to give informed consent in acute psychosis is associated with symptoms rather than diagnosis.

To investigate the association between competence to give informed consent to treatment, specific symptomology and diagnostic category, 110 inpatients diagnosed with DSM-IV acute schizophrenia (n = 64), schizoaffective disorder (n = 25) and bipolar affective disorder (n = 21) were interviewed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the Positive and Negative Syndrome Scale (PANSS). Results indicated no significant difference in competence between the three disorders. Elevated positive, cognitive and excitement PANSS factor scores had lower MacCAT-T scores. Further analyses indicated symptoms that impair cognition; particularly, conceptual disorganisation and poor attention were most consistently related to poor performance on competence tests.

A change in the density of [(3)H]flumazenil, but not [(3)H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder.

BACKGROUND: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. METHODS: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). RESULTS: Compared to tissue from schizophrenic (mean+/-S.E.M, 385+/-44 fmol/mg ETE) and control (383+/-44 fmol/mg ETE) subjects, there was an increase in the density of [(3)H]flumazenil binding to the benzodiazepine binding site on the GABA(A) receptor in subjects with bipolar disorder (451+/-17 fmol/mg ETE; P<0.05). There was no difference in the density of [(3)H]muscimol binding to the GABA(A) receptor or in the density of the serotonin(1A) receptor, serotonin(2A) receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [(3)H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. LIMITATIONS: This study involved a relatively small number of individuals. CONCLUSIONS: An increase in the gamma2-receptor sub-unit in the GABA(A) receptor has been shown to increase benzodiazepine but not [(3)H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABA(A) receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.

The new antipsychotics. How much better are they?

BACKGROUND: Despite considerable efficacy, conventional antipsychotics cause debilitating extrapyramidal side effects and may worsen 'negative' symptoms of schizophrenia. New atypical antipsychotics (clozapine, risperidone, olanzapine) have become available, and quetiepine is expected shortly; it is TGA approved and is currently available to psychiatrists through a familiarization program. OBJECTIVE: To inform general practitioners about the novel antipsychotics and their therapeutic role in contrast to conventional antipsychotic drugs. DISCUSSION: The major benefit offered by atypical antipsychotics is that these drugs are less likely to cause distressing and disabling extrapyramidal side effects at therapeutically effective doses than conventional drugs. Advantages in terms of efficacy are marginal, though clozapine is superior to conventional drugs in treatment resistant patients. The new drugs are not without other side effects. Clozapine can cause agranulocytosis, needs ongoing haematological monitoring and is only available through specialist centres. However, the new drugs do improve overall outcome. Use of risperidone, olanzapine and quetiepine is now widely recommended in preference to conventional drugs, while clozapine is used when other drugs have failed.

New developments in schizophrenia.

BACKGROUND: Over 2% of the population suffer from schizophrenia and related psychoses. Virtually all sufferers now live in the community, and go to see their general practitioners. OBJECTIVE: To overview recent developments in the presentation and causes of schizophrenia and its treatment with medication and psychosocial intervention. DISCUSSION: The diagnostic boundaries of schizophrenia have become less distinct as aetiological and therapeutic similarities between schizoaffective and affective psychoses have emerged. The importance of specific symptom groups (positive, negative, cognitive, manic, depressed) with respect to brain mechanisms and response to treatment has been recognised. It is now thought that recognition of early phase illness and vigorous treatment aimed at relapse prevention may improve long term prognosis. Availability of new medications has improved outcomes. Patients with schizophrenia living in the community need a range of services best delivered through collaborative care between GPs, community and specialist services.

No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.

Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.

Use of antipsychosis and adjunctive medications by an inner urban community psychiatric service.

OBJECTIVE: The aim of this paper is to survey patterns of use of new generation and conventional antipsychosis and adjunctive drugs by an inner urban community psychiatric service. METHOD: All prescriptions for antipsychosis medications and all patients receiving these drugs in May 1998 were identified. Case record review yielded demographic and diagnostic data. Information was also obtained directly from prescribers. RESULTS: Of 859 patients, 77% received antipsychosis medication; 53% of prescriptions for antipsychotics were for new generation drugs: risperidone (42%), olanzapine (37%) and clozapine (21%). Mean doses were 4.1+/-2.5 mg (risperidone), 14.7+/-8.2 mg (olanzapine) and 377.4+/-178.9 mg (clozapine). Doses for men tended to be higher than those for women, but the differences were not significant. DSM-IV diagnosis was schizophrenia for 74% of patients on atypicals, but patients with other diagnoses were also being treated with these drugs. Risperidone was more commonly used in combination with benzodiazepines and anticholinergics than olanzapine and clozapine, while clozapine was less likely to be combined with antidepressants and mood stabilisers. Of the conventionals, 66% were in depot form, mostly because of non-compliance. Combinations of antipsychotics were prescribed to 13% of patients. CONCLUSION: New generation antipsychosis medications were prescribed more commonly than conventional drugs in this service for a wide range of diagnoses. Adjunctive medications were commonly utilised. These findings underline the clinical complexity of antipsychotic treatment in a changing environment.

Risperidone (Risperdal): clinical experience with a new antipsychosis drug.

Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychotic symptoms, probably more so than the older neuroleptics for both positive and negative symptoms. At clinically effective doses, risperidone causes no more extrapyramidal side-effects (EPS) than placebo; at higher doses EPS frequency increases in a dose-dependent manner. Since it became available in 1994, extensive experience with the drug supports favourable early impressions of efficacy and tolerability. Minimal sedation, relatively little weight gain and absence of anticholinergic manifestations contribute to the relative tolerability of risperidone as compared to older neuroleptics. However, risperidone is associated with hyperprolactinaemia which can result in amenorrhoea and sexual dysfunction. Compared to older neuroleptics, pharmacoeconomic studies have shown that use of risperidone is associated with reduced hospitalisation and direct cost savings. A recent study found equivalent efficacy between risperidone and clozapine for treatment-resistant patients. Two studies comparing risperidone and olanzapine have yielded positive but conflicting findings. The overall positive experience with risperidone has resulted in the drug being widely recommended as a first line treatment option for psychoses.

Clozapine treatment in Australia: a review of haematological monitoring.

BACKGROUND: Clozapine is an atypical antipsychotic drug indicated for patients with schizophrenia in whom traditional antipsychotic drugs (such as haloperidol or the phenothiazines) are ineffective, or in those who experience intolerable adverse effects. Clozapine treatment may be complicated by the development of life-threatening agranulocytosis, so regular haematological monitoring is required. OBJECTIVES: To determine the incidence of clozapine-induced agranulocytosis in Australia and the importance of monitoring white blood cell counts in patients treated with clozapine. DESIGN: Review of haematological monitoring for the first three years (June 1993-July 1996) of operation of the Australian Clozaril (clozapine; Novartis Australia) Patient Monitoring System (CPMS) central database. RESULTS: In the 4061 patients prospectively monitored by the CPMS, the incidence of agranulocytosis, neutropenia and leukopenia combined was 2.6% (n = 104); the incidence of agranulocytosis was 0.9% (n = 37). So far there have been no deaths in Australia from the complications of clozapine-induced agranulocytosis. CONCLUSION: The incidence of agranulocytosis and neutropenia associated with clozapine use in Australia is similar to that in the rest of the world. Monitoring the white blood cell counts of patients being treated with clozapine ensures minimal risk to patients who develop agranulocytosis.

Confirmation of the diagnosis of schizophrenia after death using DSM-IV: a Victorian experience.

OBJECTIVE: This study examines the reliability of antemortem diagnoses of schizophrenia using DSM-IV criteria. METHOD: The case histories of 83 subjects with a provisional diagnosis of schizophrenia at autopsy were retrospectively reviewed using a semi-structured chart review and application of DSM-IV criteria. Agreement between antemortem and postmortem diagnoses of schizophrenia was examined, as well as the concordance between DSM-IV diagnoses and previously obtained diagnoses using DSM-III-R and ICD-10 criteria for schizophrenia. RESULTS: According to DSM-IV, 30.1% of cases did not have schizophrenia, compared to 36.1% using DSM-III-R criteria and 51.8% of cases using ICD-10 criteria. Concordance between DSM-IV and DSM-III-R diagnoses of schizophrenia was excellent (kappa = 0.81), but only fair between DSM-IV and ICD-10 (kappa = 0.57). Of the cases that did not meet the formal criteria for schizophrenia, the majority were reassigned diagnoses of schizoaffective disorder and affective disorder. CONCLUSIONS: The use of human brain tissue in postmortem studies of schizophrenia must be linked to standardised diagnostic assessment procedures. Diagnoses can be upgraded with the development of new criteria, providing sufficient clinical data is available in case histories.

Risperidone versus haloperidol: I. Meta-analysis of efficacy and safety.

Haloperidol is widely considered a reference standard in antipsychotic therapy and is commonly used in comparative studies of the efficacy and safety of antipsychotic medication. Comparative clinical trials have shown that the novel antipsychotic agent risperidone tends to have greater efficacy (i.e., clinical response defined as a > or = 20% reduction in total scores on the Positive and Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and Laird's random-effects model to analyze pooled patient data from available randomized, double-masked, comparative trials of risperidone and haloperidol in patients with schizophrenia treated for at least 4 weeks at recommended doses. The purpose of the analysis was to determine whether there are significant overall differences in the rates of patient clinical response, prescription of anticholinergic agents, and treatment dropout. Six of the nine trials revealed in a literature search met all criteria for inclusion in the meta-analysis. The meta-analysis showed that in patients with chronic schizophrenia, risperidone therapy is associated with significantly higher response rates, significantly less prescribing of anticholinergic medication, and significantly lower treatment dropout rates than haloperidol. These results demonstrate the greater treatment efficacy associated with risperidone compared with haloperidol and suggest both a lower incidence of EPS and improved treatment compliance.

Risperidone versus haloperidol: II. Cost-effectiveness.

Australia and Canada are currently the only Western nations with government guidelines for analyzing the cost-effectiveness of drugs. We used guidelines issued by the Australian Pharmaceutical Benefits Advisory Committee to construct a model for comparing the cost-effectiveness of risperidone and haloperidol over a 2-year period in patients with chronic schizophrenia. Use of clozapine was also included in the analysis as an alternative treatment given to patients who proved unresponsive to therapy with haloperidol or risperidone. Results are expressed in Australian dollars. Cost-effectiveness was determined by using decision-analytic modeling to compare clinical outcomes and costs. The analytic model contained a decision tree for each of the compared agents that tracked the distribution of patients between treatment outcome pathways (i.e., scenarios). Distributions were based on probabilities derived from our meta-analysis results reported elsewhere and from other sources. Each scenario had an associated monetary cost that included all significant direct costs (i.e., hospital costs; outpatient costs; and the cost of drugs, the services of health care professionals, and government-subsidized hostel accommodation). The cost for a given outcome was the sum of costs for all scenarios leading to that outcome. Cost-effectiveness was expressed as the total cost per favorable outcome. The definition of a favorable outcome was one in which the patient was in a response phase at the end of the 2-year period. The probability of a patient experiencing a favorable outcome at the end of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for haloperidol. The expected cost per favorable outcome was $19,709.00 for risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective than haloperidol and therefore was "dominant" in pharmacoeconomic terms because it produced a higher proportion of favorable outcomes at lower cost. Sensitivity analysis showed that the difference in clinical response rate was a key determinant of cost-effectiveness.

The binding of both [3H]nemonapride and [3H]raclopride is increased in schizophrenia.

We performed a postmortem autoradiographic study to compare the density of dopamine D4-like sites in caudate putamen section from age-matched schizophrenia (n = 15) and control (n = 15) populations. The densities of the D4-like sites were estimated by subtracting the density of [3H]raclopride (binding D2 and D3 receptors) from the density of [3H]nemonapride (binding D2, D3, and D4 receptors). The findings revealed that in the schizophrenia population there was a significant increase in the binding of both [3H]nemonapride (2.3-fold) and [3H]raclopride (1.9-fold). In addition, in the schizophrenia population the density of D4-like sites was increased 2.6-fold.

Cognitive-existential group therapy for patients with primary breast cancer--techniques and themes.

We describe a model of cognitive-existential group therapy designed to be integrated over 6 months with regimens of adjuvant chemotherapy given as conventional medical treatment to breast cancer patients with stage 1 and 2 disease. Our broad therapy goals are for members to develop a supportive network, work through grief over losses, improve problem solving and develop cognitive strategies to maximise coping, enhance a sense of mastery over life and re-evaluate priorities for the future. Specific group themes include death anxiety, fear of recurrence, living with uncertainty, understanding treatment with chemotherapy, radiotherapy and hormone regimens, the collaborative doctor-patient relationship, body and self image, sexuality, relationships with partner, friends and family, surgical reconstruction, life style effects and future goals. Active coping skills are developed through teaching formal problem solving and cognitive restructuring of automatic negative thoughts. Technical aspects of the therapy are discussed.

Impact of newer antipsychotics on outcomes in schizophrenia.

Functional status in schizophrenia depends in part on cognitive function. Newer antipsychotics, such as risperidone, produce better cognitive function in patients with schizophrenia than do conventional neuroleptics, which implies that the indirect costs of the illness will be less in patients treated with risperidone. A robust decision-analytic model of schizophrenia suggests that the overall cost of treating a patient with risperidone is $11,772.00 per year compared with $13,622.00 per year for haloperidol and that the cost per response is even more favorable toward risperidone--$14,599.00 versus $23,040.00. This model supports the results of naturalistic trials in which risperidone produced better outcomes than did conventional neuroleptics. Overall, the use of the more effective, better tolerated newer antipsychotics should reduce the cost to society of schizophrenia and improve patients' quality of life.