Early access to clozapine in Early Intervention in Psychosis: Hope vs reality. A mixed method service analysis.

AIM: Improving access to clozapine is a recognized priority nationally across Early Intervention in Psychosis Services (EIPS) in the UK. Treatment resistance (TR) may be identifiable from early episode psychosis and appears to be characterized by negative symptoms and younger age of onset. This mixed method cross-sectional snapshot analysis of antipsychotic (AP) prescribing in an EIPS, explored clozapine eligibility (CE) and prioritization of AP prescribing based on choice, selectivity and appropriateness. METHOD: We screened 150 service users and 79% (n = 119) were retained after inclusion criteria were applied. We explored CE in all service users who were indicated clozapine based on the product licence (n = 78), and whether there was association between CE and number of hospital admissions, AP trials, age at first episode and duration of untreated psychosis. RESULTS: Following multidisciplinary clinical discussions, we found that 23 service users were CE; 8 were offered and declined clozapine. When compared to non-CE service users, significant factors associated with CE were history of two or more hospital admissions (Mann-Whitney U = 269, P = .008), more than two trials of two different APs (Mann-Whitney U = 517, P ≤ .01), and younger age first episode (independent-samples t-test, P = .047). A total of 47.5% of all service users had been started on olanzapine as their first AP, despite high risk of cardiometabolic syndrome. CONCLUSION: We propose that EIP services adopt a proactive approach in screening for TR, taking into account negative symptoms and young age at onset, prioritizing service users with two or more hospital admissions and AP trials.

Effectiveness of antipsychotics used in first-episode psychosis: a naturalistic cohort study.

BACKGROUND: One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP). AIMS: To investigate the effectiveness of commonly used antipsychotic medications in FEP. METHOD: A retrospective cohort study of naturalistic treatment of patients (N=460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files. RESULTS: Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation. CONCLUSIONS: Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus. DECLARATION OF INTEREST: R.W., A.T. and S.M. have received research grant, speaker honoraria and conference attendance funding from all companies marketing antipsychotics. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production.

BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1beta, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-alpha, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5-7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5-7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1beta, TNF-alpha and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS.