Nagesh Pai

Olanzapine and clozapine, two of the most efficacious second-generation antipsychotic drugs (SGAs), are known to cause serious metabolic side effects. Despite their clinical utility, the epigenetic basis of these metabolic side-effects remains poorly understood. This exploratory study investigated whether histone methylation is associated with metabolic disorders following chronic SGA treatment. Rats were treated with olanzapine or clozapine for 9 weeks and then sacrificed 2 h after the final treatment. After evaluating the metabolic parameters, Chromatin immunoprecipitation (ChIP)-deep sequencing was conducted on liver tissue pooled from twelve samples per group to quantify histone H3K4me2 methylation and transcriptional changes. Gene ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore shared functional pathways of genes with differential histone methylation. Key findings revealed that both olanzapine and clozapine induced widespread changes in hepatic histone methylation, particularly hypermethylation at H3K4me2 across genes involved in lipid and glucose metabolism, insulin signalling, and adipogenesis. Olanzapine- and clozapine-treated rats displayed increased H3K4me2 levels at numerous gene loci and at distinct genomic regions. These findings suggest the importance of monitoring metabolic parameters in psychiatric patients and potential novel strategies to mitigate SGA-induced metabolic side effects.

Background: To examine real-world patterns of antipsychotic use in patients with schizophrenia Australia. Methods: This retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample data. Included data were for patients aged 16-years or older who initiated treatment for the first time with a PBS-reimbursed antipsychotic medication for schizophrenia between July 2013 and September 2017. Patterns of treatment usage were summarised descriptively. Differences in prescribing patterns by age and prescribing year were reported. Treatment persistence was estimated using Kaplan-Meier methods, with differences explored using log-rank tests. Values of p < 0.05 were considered statistically significant. Results: 6,740 patients, representing 8,249 non-unique patients, received prescriptions for antipsychotic medications. Patients were aged 16 years to over 85 years (54.5% were < 55 years) and two-thirds of patients were male (61%). The majority of treatment episodes (62%, n = 5,139/8,249) were prescribed an atypical oral antipsychotic. Typical long-acting antipsychotic therapies (LATs) were prescribed 19% of the treatment episodes (n = 1,608/8,249. There was a small increase in prescribing of atypical LAT and typical LAT and a small decrease in atypical oral and clozapine prescribing over the study period. Treatment persistence was greatest in patients treated with clozapine, than in those treated with atypical LATs. Conclusions: While the majority of patients receive atypical antipsychotic medications, one in five continue to use older typical LAT therapies. Patient age and time on therapy may be associated with choice of therapy. Persistence to atypical LAT therapy is better than for other treatment modalities in this real-world cohort.

This study examined the association between neighbourhood socioeconomic disadvantage and serious mental illness (SMI)–type 2 diabetes (T2D) comorbidity in an Australian population using routinely collected clinical data. We hypothesised that neighbourhood socioeconomic disadvantage is positively associated with T2D comorbidity in SMI. The analysis considered 3816 individuals with an SMI living in the Illawarra and Shoalhaven regions of NSW, Australia, between 2010 and 2017. Multilevel logistic regression models accounting for suburb (neighbourhood) level clustering were used to assess the association between neighbourhood disadvantage and SMI -T2D comorbidity. Models were adjusted for age, sex, and country of birth. Compared with the most advantaged neighbourhoods, residents in the most disadvantaged neighbourhoods had 3.2 times greater odds of having SMI–T2D comorbidity even after controlling for confounding factors (OR 3.20, 95% CI 1.42–7.20). The analysis also revealed significant geographic variation in the distribution of SMI -T2D comorbidity in our sample (Median Odds Ratio = 1.35) Neighbourhood socioeconomic disadvantage accounted for approximately 17.3% of this geographic variation. These findings indicate a potentially important role for geographically targeted initiatives designed to enhance prevention and management of SMI–T2D comorbidity in disadvantaged communities.

Objectives: Real-world experience from a 6-month product familiarization programme (PFP) for 3-monthly paliperidone palmitate in schizophrenia maintenance treatment. Methods: Prescribers completed an online questionnaire for each patient at enrolment with further questions at second dose (re-supply) stage and a second survey of their overall experience at the end. Results: Ninety-four patients were enrolled and received a first dose and 23 received a second dose within the 6-month programme; 51.1% had been hospitalised for symptom relapse in the previous 2 years. Reasons for prescribing were convenience of 3-monthly dosing for patients (94.7%) and patient choice (54.6%). Prescribers followed-up at least once-monthly (69.6% cases) and indicated in 48.9% they would consider shared GP care. All patients were satisfied with symptom control and either maintained functioning or showed improvement. Clinicians felt confident with administration and identifying suitable patients and were all ‘satisfied’ or ‘somewhat satisfied’ with efficacy and tolerability. All felt patients’ treatment goals were either ‘met’ (81.3%) or ‘partly met’ (18.7%) and none reported dissatisfaction with relapse prevention. Conclusions: Convenient 3-monthly dosing was preferred by clinicians and patients, and symptoms were adequately managed. This has the potential to improve adherence and lead to better outcomes as patients only need four intramuscular doses per year.

Role of environment on mental health cannot be ignored. Computer based mapping technology called Geographical Information Systems (GIS) has presented mental health researchers with many new possibilities to explore these relationships. The main aim of this literature review is to identify the emerging applications of GIS in mental health research. The use of GIS in mental health has faltered compared to other health care sectors and has started gaining momentum only in the recent years. There is great scope for GIS to be applied in mental health epidemiology, evaluating inequalities in health care access, determining spatial variation in service utilisation and planning health care delivery and community integration. The technology is bound to find many more innovative applications in the mental health care sector in the coming years