Risk of readmission in patients with schizophrenia and schizoaffective disorder newly prescribed clozapine.

BACKGROUND: Insight into the effect of clozapine is limited by a lack of controlling for confounding variables in current research. Our objective was to investigate the association between clozapine prescribed at discharge, following an inpatient episode, and risk of readmission into secondary mental health services in patients with schizophrenia and schizoaffective disorder, controlling extensively for confounding variables. METHODS: Clinical records from 3651 patients were analysed in a retrospective observational cohort study. Cox proportional-hazards regression models were used to assess the risk of hospital readmission. A series of sensitivity analyses were also conducted. Propensity score methods were used to address confounding-by-indication. RESULTS: Patients on clozapine ( n=202) had a reduced risk of readmission compared with patients on other antipsychotics (adjusted hazard ratio=0.79; 95% confidence interval: 0.64-0.99; p=0.043). Clozapine also had a protective effect on risk of readmission when compared with olanzapine (adjusted hazard ratio 0.76; 95% confidence interval: 0.60-0.96; p=0.021). The effect size remained consistent after adjusting for an array of possible confounders, as well as using propensity scores to address confounding-by-indication. A statistically significant result was also noted in all but two sensitivity analyses. CONCLUSION: Our findings suggest that clozapine is associated with a reduced risk of readmission into secondary mental health services.

Antipsychotic polypharmacy prescribing and risk of hospital readmission.

OBJECTIVES: The aim of this study was to determine if there was an association between being discharged on antipsychotic polypharmacy (APP) and risk of readmission into secondary mental health care. METHODS: Using data from the South London and Maudsley (SLAM) case register, service users with serious mental illness (SMI), discharged between 1st January 2007 and 31th December 2014, were followed up for 6 months. Patients were classified as receiving either monotherapy or polypharmacy at index discharge. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical and service use factors. RESULTS: We identified 5523 adults who had been admitted at least once to SLAM, of whom 1355 (24.5%) were readmitted into secondary mental health care. In total, 15% (n = 826) of patients were discharged on APP and 85% (n = 4697) on monotherapy. Of these, 30.9% (n = 255) and 23.4% (n = 1100) were readmitted respectively. Being discharged on APP was associated with a significantly increased risk of readmission, in comparison to patients discharged on monotherapy (HR = 1.4, 1.2-1.7, p < 0.001). This association was maintained in the fully adjusted model and following several sensitivity analyses. We further established that patients receiving clozapine APP (n = 200) were at a significantly increased risk for readmission in comparison to patients on clozapine monotherapy (HR = 1.8, 1.2-2.6, p = 0.008). CONCLUSIONS: Our results suggest that patients discharged on APP are more likely to be readmitted into hospital within 6 months in comparison to those discharged on monotherapy. This needs to be considered in treatment decisions and the reasons for the association clarified.

Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors.