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Background: Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine. Objective and methods: Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context. Results: A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocyte-colony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported. Conclusion: Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed. [ABSTRACT FROM AUTHOR]

Background: Risk factors for obstructive sleep apnea (OSA) are common in people with schizophrenia. Identification and treatment of OSA may improve physical health in this population; however there are no guidelines to inform screening and management.Objectives: Systematic review to determine, in people with schizophrenia and related disorders: the prevalence of OSA; the prevalence of OSA compared to general population controls; the physical and psychiatric correlates of OSA, associations between antipsychotic medications and OSA; the impact of treatment of OSA on psychiatric and physical health; and the diagnostic validity of OSA screening tools.Data Sources: Medline, EMBASE, ISI Web of Science and PsycINFO electronic databases. Cohort, case-control and cross-sectional studies and RCTs reporting on prevalence of OSA in subjects with schizophrenia and related disorders were reviewed.Results: The prevalence of OSA varied between 1.6% and 52%. The prevalence of OSA was similar between people with schizophrenia and population controls in two studies. Diagnosis of OSA was associated with larger neck circumference, BMI>25, male sex and age>50years. There were no data on physical or psychiatric outcomes following treatment of OSA. The diagnostic utility of OSA screening tools had not been investigated.Conclusion: OSA may be prevalent and potentially under-recognized in people with schizophrenia. Further research is required to determine utility of OSA screening tools, the relationships between antipsychotic medications and OSA and any benefits of treating OSA. We propose a strategy for the identification of OSA in people with schizophrenia and related disorders. [ABSTRACT FROM AUTHOR]

Background: There is a well-established but poorly understood association between tobacco use and psychotic illness. The aim of this study was to determine whether tobacco use is associated with an earlier age at onset of psychotic illness. Methods: Peer-reviewed publications in English reporting the age at onset of psychosis in tobacco-using and non-tobacco-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO and ISI Web of Science, and were supplemented by papers located by manual searches and unpublished data obtained by correspondence with primary researchers. A total of 29 samples reported age at onset data in a consecutive series of patients with a diagnosis of schizophrenia related psychosis or first episode psychosis. Information on study design, study population and effect size was extracted independently by three authors. A random effects meta-analysis was performed. Results: There was no significant difference between smokers and non-smokers in age at the onset of psychosis (standardized mean difference = −0.03). Conclusion: Unlike cannabis use, tobacco use is not associated with an earlier onset of psychosis. [ABSTRACT FROM AUTHOR]

Objectives:: Obstructive sleep apnoea (OSA) may be more common in people with schizophrenia compared to the general population, but the relative prevalence is unknown. Here, we determine the relative prevalence of severe OSA in a cohort of men with schizophrenia compared to representative general population controls, and investigate the contribution of age and body mass index (BMI) to differences in prevalence.Methods:: Rates of severe OSA (apnoea-hypopnoea index > 30) were compared between male patients with schizophrenia and controls from a representative general population study of OSA.Results:: The prevalence of severe OSA was 25% in the schizophrenia group and 12.3% in the general population group. In subgroups matched by age, the relative risk of severe OSA was 2.9 ( p = 0.05) in the schizophrenia subjects, but when adjusted for age and BMI, the relative risk dropped to 1.7 and became non-significant ( p = 0.17).Conclusions:: OSA is prevalent in men with schizophrenia. Obesity may be an important contributing factor to the increased rate of OSA. [ABSTRACT FROM AUTHOR]

Background: Clozapine is the most effective medication for treatment refractory schizophrenia, but is associated with cardiac adverse drug reactions. Myocarditis and cardiomyopathy are the most serious cardiac adverse drug reactions although reported rates of these conditions vary in the literature. We systematically reviewed and meta-analysed the event rates, the absolute death rates and case fatality rates of myocarditis and cardiomyopathy associated with clozapine. Methods: PubMed, EMBASE and PsycINFO were searched for studies that reported on the incidence of cardiomyopathy or myocarditis in people exposed to clozapine. Data were meta-analysed using a random effects model, with subgroup analysis on study size, time frame, region, quality, retrospective vs prospective, and diagnostic criteria of myocarditis or cardiomyopathy. Results: 28 studies of 258,961 people exposed to clozapine were included. The event rate of myocarditis was 0.007 (95% confidence interval [CI] = [0.003, 0.016]), absolute death rate was 0.0004 (95% CI = [0.0002, 0.0009]) and case fatality rate was 0.127 (95% CI = [0.034, 0.377]). The cardiomyopathy event rate was 0.006 (95% CI = [0.002, 0.023]), absolute death rate was 0.0003 (95% CI = [0.0001, 0.0012]) and case fatality rate was 0.078 (95% CI = [0.018, 0.285]). Few included studies provided information on criteria for diagnosis of myocarditis and cardiomyopathy. Event rates of cardiomyopathy and myocarditis were higher in Australia. Conclusion: Clarity of diagnostic criteria for myocarditis remains a challenge. Observation bias may, in part, influence higher reported rates in Australia. Monitoring for myocarditis is warranted in the first 4 weeks, and treatment of comorbid metabolic syndrome and diabetes may reduce the risk of cardiomyopathy. The risks of myocarditis and cardiomyopathy are low and should not present a barrier to people with treatment refractory schizophrenia being offered a monitored trial of clozapine. [ABSTRACT FROM AUTHOR]