Nicholas Keks

A clinical trial of the effects of estrogen in acutely psychotic women.

This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia.

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.

Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.

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.

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine

Summary[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd=0.50 ± 0.04 vs. 0.24 ± 0.02nM; mean ± S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd=0.50 ± 0.07 vs. 0.50 ± 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

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.

SUICIDE AND SCHIZOPHRENIA: A REVIEW OF LITERATURE FOR THE DECADE (1990-1999) AND IMPLICATIONS FOR MENTAL HEALTH NURSING

This paper presents an overview of recent evidence on general and specific risk factors for suicide in patients with schizophrenia. The authors highlight the significant factors contributing to the likelihood of suicide in patients diagnosed with schizophrenia. This information will enhance the delivery of nursing care to these patients in all health care settings. A review of literature was conducted by two methods of investigation: Medline and CINAHL search and a manual search through articles from 1990 to 1999. The lifetime risk of committing suicide is estimated at about 9-13% of persons with schizophrenia, and it is 20 to 50 times higher than that in the general population. Young white males diagnosed with schizophrenia who are depressed, unmarried, unemployed, socially isolated, and functionally impaired and who lack external support are the most vulnerable in the early stages of schizophrenic illness. Findings can be instrumental in identifying and treating patients who are most vulnerable and in making psychiatric nurses aware of the scenarios and critical stages of the disease process when suicide is most likely to occur.

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 Brodmanns 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 (Brodmanns 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.

EXPLORING THE COMPLEXITY OF COMPLIANCE IN SCHIZOPHRENIA

A large body of literature indicates that people diagnosed with schizophrenia are highly likely to not comply with their prescribed treatment regime at some stage during the illness process. Factors that indicate the risk of noncompliance have been the subject of considerable research over a number of years. This paper presents an extensive review of the research literature on the subject of compliance in schizophrenia. A number of factors have constituted the focus of research into this area. These include: socio-demographic characteristics, including age, gender and socioeconomic status; illness factors including insight, psychiatric symptomatology, duration of illness, substance abuse, and adverse side-effects of medication; psychosocial factors such as health beliefs and social supports; and treatment factors including the nature of the therapeutic relationship between patients and health care professionals. While the results of relevant research do not provide a clear and conclusive picture of compliance, they provide important information to guide the pivotal role of the mental health nurse in facilitating patient compliance.

Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia

SummaryChanges in G-protein linked neurotransmitter receptors have been reported in a number of regions of the brain of schizophrenic subjects. These changes, if functional, could cause a change in proteins such as protein kinase C (PKC) and adenylate cyclase (AC) which are important components of the G-protein linked second messenger cascades. We therefore used autoradiography to measure the distribution and density of [3H]phorbol ester binding to PKC and [3H]forskolin binding to AC in tissue obtained at autopsy from schizophrenic and non-schizophrenic subjects (Controls). There were significant decreases in the density of PKC in the parahippocampal gyrus (687 ± 60 vs. 885 ± 51fmol/mg TE; mean ± SEM; p < 0.01) and in AC in the dentate gyrus (75 ± 4.9 vs. 92 ± 6.5, p < 0.05) from the schizophrenic subjects. These data could indicate that changes in neurotransmitter receptors in the hippocampus from subjects with schizophrenia could have resulted in a change in their associated second messenger systems.