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.

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.

Minimizing the non-extrapyramidal side-effects of antipsychotics.

Standard neuroleptic medications have been augmented by the introduction of risperidone and clozapine into clinical practice. A great deal of attention has also been focused on efficacy and the lower propensity to extrapyramidal side-effects associated with the new agents. However, antipsychotic medication, both old and new, can cause a range of other adverse effects, some of which are serious, and many of which have the potential greatly to diminish the quality of life of patients who need to take medication in the long term. Of particular significance are postural hypotension, cardiotoxicity, peripheral and central anticholinergic effects, sedation, weight gain, and endocrine and haematological effects. Various antipsychotic compounds differ substantially with regard to propensity to adverse effects. Side-effects can be minimized by optimization of clinical strategies, including choice of appropriate drug, slow titration and dosage reduction. It is also vital to explain carefully to both patients and carers the nature of the side-effects which can be anticipated. The choice of antipsychotic is often determined by evaluation of the potential impact of the various adverse effects on a particular patient. New drugs, such as risperidone, are well tolerated, with fewer side-effects, and should now be considered as a first-line option.

Basal and haloperidol-stimulated prolactin and symptoms of nonaffective and affective psychoses in neuroleptic-free men.

The prolactin (PRL) response to 0.5 mg of intravenous haloperidol (HPL) IV may be a measure of tuberoinfundibular dopaminergic activity. Our earlier reports, using multidiagnostic strategies in schizophrenia, suggested that psychoses characterized by the absence of affective syndromes (Keks et al 1990) and the presence of thought disorder and passivity delusions (Keks et al 1992) are linked to blunted PRL responses. In this paper we evaluated the relationships between basal and HPL-stimulated PRL concentrations, and a number of potentially relevant symptom measures. Basal PRL was lower in patients without a depressive syndrome and suicidal ideation. Stimulated PRL was lower in patients without neurovegetative symptoms (versus patients with neurovegetative symptoms and controls), with depression (versus patients with no depression and controls) and those with disorder of associations (versus patients without association disturbance and controls). These findings can be interpreted as indicating a link between endocrine measures of dopaminergic function and a subtype of schizophrenic psychosis characterized by the presence of thinking disturbance in the absence of depression.