High rates of myocarditis with clozapine in the Hunter region of Australia.

OBJECTIVE: To study the causes of clozapine treatment discontinuation and measure clozapine-induced myocarditis (CIM) rates in an Australian region, to compare the observed rates of CMI with reports from Australia and the world, and discuss factors related to CIM incidence rates in the region. METHODS: The study is a retrospective clinical audit of 327 patients prescribed clozapine. All patients were monitored by the mandatory CIM monitoring protocol for the first six weeks of treatment. The validity of a diagnosis of CIM was assessed using six criteria. Socio-demographic and clinical factors and clozapine prescription practices were analysed for their association with CIM. The study could not examine co-existing medical illness, co-prescribed psychotropic medication, genetics, and environmental factors. RESULTS: CIM occurred in 9.8 % of the cohort after a mean treatment duration of 19.5 days. The diagnosis of CIM was considered valid in all cases. Gender, age at the start of treatment, ethnicity, cumulative clozapine dose, dose titration, and clozapine/norclozapine ratio were unrelated to CIM. CONCLUSION: The CIM rate in the Hunter region was higher than in the rest of Australia and the world and increased after adopting the monitoring protocol. Over-diagnosis, patient's age and gender, ethnicity, cumulative clozapine dose, dosing titration, and clozapine metabolism rate were unrelated to the high occurrence rates. The possible role of comorbid illnesses, co-prescribed psychiatric medications, genetic, and environmental factors in the etiology of CIM requires further study. The reasons underlying the high rates of CIM in the Hunter region need further exploration.

A qualitative study of clinicians' perspectives on reasons for delays in clozapine initiation.

OBJECTIVES: To elicit mental health clinicians' views on the reasons for delayed initiation of clozapine treatment. METHOD: Thematic analysis of transcripts from a semi-structured interview of 15 mental health clinicians. RESULTS: Four major themes emerged from data analysis: Patient and Carer Factors, Medication factors, Protocol factors, and Prescriber factors. Patient and carer anxiety over side effects and experience of stigma, difficulties in implementing the monitoring protocol, problems with community managing of treatment, prescriber preferences and practices, and gaps in mental health services were some of the reasons identified. CONCLUSION: Education and support to patients and carers, a modified monitoring protocol, establishing clozapine clinics, improved early intervention services, and upskilling of clinicians can promote early clozapine initiation.

Electrocardiographic abnormalities and psychotropic polypharmacy in schizophrenia and schizoaffective disorders.

BACKGROUND: Sudden cardiac death (SCD) is a significant cause for increased mortality in people with schizophrenia and schizoaffective disorders. Cardiac arrhythmia is one cause of SCD. Electrocardiographic (ECG) abnormalities predictive of arrhythmias are associated with antipsychotic drug use. METHOD: This chart audit examined the types and frequency of ECG abnormalities (ECG-Abs) in 169 patients with schizophrenia and schizoaffective disorder in a long-stay inpatient unit. We examined the association of ECG-Abs with demographic details and psychotropic drug prescription using chi-square test, Fisher's Exact test, independent two-sample t-test, Pearson's correlation, and one-way ANOVA. RESULTS: Eighty-eight patients (52.1%) recorded at least one ECG-Ab, and 20.7% had two or more ECG-Abs. The use of multiple antipsychotics, with or without other psychotropic drugs, did not associate significantly with the presence or number of ECG-Abs. CONCLUSION: A significant proportion of patients with schizophrenia and schizoaffective disorder have ECG-Abs other than prolonged QTc interval, which can predispose them to cardiac arrhythmias. The abnormalities were not limited to patients on psychotropic polypharmacy. ECG evaluation is indicated for all patients and should consider various electrical abnormalities to identify arrhythmia risk.

Serum lipids and suicidal risk among patients with schizophrenia spectrum disorders: Systematic review and meta-analysis.

OBJECTIVE: A systematic review of literature was conducted to determine the association between serum lipids and suicidality in people with schizophrenia spectrum disorders. METHODS: We undertook a systematic search of multiple databases for studies that ascertained an association between serum lipids and suicidality in adult patients with schizophrenia spectrum disorders (18-65 years) from database inception to 2 September 2020. Qualitative analysis was done using National Institute of Health (NIH) scales. The standard mean difference (SMD) and 95% confidence intervals (CI) were calculated for each study and standardized relative to the study. Adjusted p-value, Z-test, and heterogeneity were calculated, as well as testing for publication bias. RESULTS: Of 1262 records identified, 17 studies (n = 3113) were included in our systematic review, while 11 studies were included in the meta-analysis. The majority of studies (11) rated fair on qualitative analysis. Data from seven studies (n = 1597) revealed a medium effect size for an association between low total cholesterol and suicide attempts (SMD -0.560; 95% CI: 0.949-0.170; p = 0.005). People with history of suicide attempt had a mean cholesterol value 0.56 SD lower than the mean in those without suicide attempts. There were differences in how a suicide attempt was defined and there was high heterogeneity (I2 = 83.3%). No significant association was found between any of the serum lipid parameters and suicide ideation. Funnel-plot analysis suggested small study effects with publication bias. CONCLUSIONS: Suicide attempts in people with schizophrenia spectrum disorders are associated with low mean total cholesterol levels.

Continuation of Treatment With Clozapine After an Episode of Neutropenia.

BACKGROUND: Clozapine is the most effective in treatment-resistant schizophrenia. Neutropenia is an adverse effect of the drug requiring treatment discontinuation. This study related treatment continuation with little or no interruption after a neutropenia episode. The study contrasted from rechallenge studies after an extended treatment interruption. METHODS: This retrospective chart audit examined 37 patients with an episode of neutropenia. It described characteristics of patients continuing treatment with minimal interruption. FINDINGS: Thirty-one patients continued treatment after an initial treatment interruption for less than 3 days. A probable cause for neutropenia other than clozapine was identified in 14 patients. Twelve patients continued treatment with a change in the absolute neutrophil counts threshold to 1000/µL to determine treatment cessation. Most patients recovered from the index episode of neutropenia within 2 days. They also frequently presented with recurring benign episodes of low neutrophil cell counts during treatment than a comparative group. IMPLICATIONS: The study recommends modifying clozapine treatment protocol absolute neutrophil count thresholds to less than 1000/µL to determine treatment cessation. Consideration of other probable causes for neutropenia, diurnal variations in cell counts, and laboratory errors reduced preemptive discontinuation of treatment. A risk-benefit approach supports continuing clozapine treatment after an episode of neutropenia.

Care pathways, engagement and outcomes associated with a recovery-oriented intermediate stay mental health program.

This study examined care pathways, program engagement, and key outcomes associated with a sub-acute inpatient stay in a 20-bed stand-alone Intermediate Stay Mental Health Unit (ISMHU; NSW, Australia). A 6-week evidenced-based tailored intervention program was offered, utilizing a recovery-oriented model of care. Service data from multiple record systems were combined, including admissions and service contacts 2-years prior to and following the index admission. During the initial 16-months there were 146 index admissions with a length of stay greater than 7 days. The majority (75.3%) were transfers from acute-care, with an average ISMHU stay of 50.3 days. Service and clinical outcomes were examined in relation to care pathways, recovery needs, program engagement and benefits achieved. Substantial engagement was detected (e.g., 74.0% >10 intervention types), together with significant improvements on self-report and clinician rated measures (e.g., social connection, symptoms, and self-belief). Logistic regression analyses revealed that arrival category was the strongest outcome predictor, with community referrals experiencing the largest reduction in subsequent acute mental health admissions (58.3% to 16.7%), followed by involuntary inpatient referrals (80.3% to 60.7%). Potential recovery-focused benefits are not limited to community treatment settings, while pathways to care may help identify clients with differing needs and opportunities for treatment.

Schizophrenia, recovery and the individual-cultural considerations.

OBJECTIVES: The concept of recovery in mental health has been embraced by many services across the world. Placing the individual (self) at the core of service delivery constituted a profound shift from service-driven models of care. However, cultures described as individualistic or collectivist may hold very different views of individuality. In cultures with collectivist orientation, the notion of 'individualism' is integrated into the structure and dynamics of the family. The families in such cultures play a major and lifetime role in caring for its members, making decisions and acting in consideration of the welfare of all. The needs and priorities of individuals, especially women, may be superseded by those of their families. This commentary is on the effect of culture on the identity of self in the recovery process and its relevance to mental health care. CONCLUSION: In multicultural societies like Australia that include Indigenous people, the process of acculturation may be different. For the Indigenous people, the shift was from a collectivist culture to one that was predominantly individualistic. In the provision of recovery-oriented mental health care, there needs to be an awareness of the cultural variations in the relational dynamics of individualism.

Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P = .004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment.

An Integrated Recovery-oriented Model (IRM) for mental health services: evolution and challenges.

BACKGROUND: Over past decades, improvements in longer-term clinical and personal outcomes for individuals experiencing serious mental illness (SMI) have been moderate, although recovery has clearly been shown to be possible. Recovery experiences are inherently personal, and recovery can be complex and non-linear; however, there are a broad range of potential recovery contexts and contributors, both non-professional and professional. Ongoing refinement of recovery-oriented models for mental health (MH) services needs to be fostered. DISCUSSION: This descriptive paper outlines a service-wide Integrated Recovery-oriented Model (IRM) for MH services, designed to enhance personally valued health, wellbeing and social inclusion outcomes by increasing access to evidenced-based psychosocial interventions (EBIs) within a service context that supports recovery as both a process and an outcome. Evolution of the IRM is characterised as a series of five broad challenges, which draw together: relevant recovery perspectives; overall service delivery frameworks; psychiatric and psychosocial rehabilitation approaches and literature; our own clinical and service delivery experience; and implementation, evaluation and review strategies. The model revolves around the person's changing recovery needs, focusing on underlying processes and the service frameworks to support and reinforce hope as a primary catalyst for symptomatic and functional recovery. Within the IRM, clinical rehabilitation (CR) practices, processes and partnerships facilitate access to psychosocial EBIs to promote hope, recovery, self-agency and social inclusion. Core IRM components are detailed (remediation of functioning; collaborative restoration of skills and competencies; and active community reconnection), together with associated phases, processes, evaluation strategies, and an illustrative IRM scenario. The achievement of these goals requires ongoing collaboration with community organisations. CONCLUSIONS: Improved outcomes are achievable for people with a SMI. It is anticipated that the IRM will afford MH services an opportunity to validate hope, as a critical element for people with SMI in assuming responsibility and developing skills in self-agency and advocacy. Strengthening recovery-oriented practices and policies within MH services needs to occur in tandem with wide-ranging service evaluation strategies.

Implementation of a recovery-oriented model in a sub-acute Intermediate Stay Mental Health Unit (ISMHU).

BACKGROUND: An ongoing service evaluation project was initiated following the establishment of a new, purpose-built, 20-bed sub-acute Intermediate Stay Mental Health Unit (ISMHU). This paper: provides an overview of the targeted 6-week program, operating within an Integrated Recovery-oriented Model (IRM); characterises the clients admitted during the first 16 months; and documents their recovery needs and any changes. METHODS: A brief description of the unit's establishment and programs is initially provided. Client needs and priorities were identified collaboratively using the Mental Health Recovery Star (MHRS) and addressed through a range of in-situ, individual and group interventions. Extracted client and service data were analysed using descriptive statistics, paired t-tests examining change from admission to discharge, and selected correlations. RESULTS: The initial 154 clients (165 admissions, average stay = 47.86 days) were predominately male (72.1%), transferred from acute care (75.3%), with schizophrenia or related disorders (74.0%). Readmission rates within 6-months were 16.2% for acute and 3.2% for sub-acute care. Three MHRS subscales were derived, together with stage-of-change categories. Marked improvements in MHRS Symptom management and functioning were identified (z-change = -1.15), followed by Social-connection (z-change = -0.82) and Self-belief (z-change = -0.76). This was accompanied by a mean reduction of 2.59 in the number of pre-action MHRS items from admission to discharge (z-change = 0.98). Clinician-rated Health of the Nation Outcome Scales (HoNOS) improvements were smaller (z-change = 0.41), indicative of illness chronicity. Staff valued the elements of client choice, the holistic and team approach, program quality, review processes and opportunities for client change. Addressing high-levels of need in the 6-week timeframe was raised as a concern. CONCLUSIONS: This paper demonstrates that a recovery-oriented model can be successfully implemented at the intermediate level of care. It is hoped that ongoing evaluations support the enthusiasm, commitment and feedback evident from staff, clients and carers.

Metabolic syndrome in antipsychotic naïve patients with schizophrenia: pooled analysis of data from three Indian studies.

AIM: This study aimed to assess the prevalence of metabolic syndrome (MS) and subthreshold MS in antipsychotic naïve patients with schizophrenia by pooling the data from three different centres in India. METHODS: One hundred thirty-seven antipsychotic naïve patients with schizophrenia were evaluated for MS using common criteria for clinical diagnosis. RESULTS: Twenty-six patients (19%) met consensus criteria. Additionally, 56 patients (40.9%) fulfilled one criterion and 32 patients (23.3%) fulfilled two criteria of MS out of five criteria. CONCLUSION: One-fifth of antipsychotic naïve patients with schizophrenia had MS and another two-third had at least one metabolic abnormality. Awareness of such a high risk is vitally important for rational selection of antipsychotic medications as well as effective implementation of preventive measures.