Clozapine-related tachycardia: A conundrum to identify and treat.

OBJECTIVE: This study examined the rates and persistence of clozapine-induced tachycardia and heart-rate differences in patients treated with ß-blockers in the largest sample of patients with a psychotic disorder to date. METHOD: An audit of medical files for 101 patients who attended a clozapine community clinic and analysis of monthly measurements of resting heart rates. RESULTS: 51% met the clinical criteria for tachycardia. Heart rates were stable over time. ß-blockers were associated with small but significant reductions in heart rates. CONCLUSION: The cardiovascular risks of clozapine are often overlooked. ß-blockers are useful in lowering heart rates but they may be insufficient to reduce cardiac risk.

Weight changes in people with early psychosis treated with oral or long-acting injectable aripiprazole.

OBJECTIVES: Weight gain remains a major problem in young people with psychosis treated with antipsychotic medication. Aripiprazole is now available in monthly long-acting injection (LAI) and daily oral tablet formulation, but information is lacking about differences in weight gain between the two formulations. We monitored for up to 24 months the weight changes associated with oral or LAI-administered aripiprazole and in a group who not prescribed any antipsychotic medication. METHODS: Participants included 109 young people with early psychosis (n = 30 Oral, 41 LAI, 38 Nil antipsychotic) with a treatment completion median time of 15 months. Weight (kilogram) and body mass index (BMI) were recorded at 3 monthly intervals. Multilevel modelling analyses assessed the contribution of time and group on weight change. RESULTS: Participants taking nil antipsychotics did not gain weight over time, while the two aripiprazole groups gained a combined average of 7.1 kg (SD = 5.0) or 1.9 BMI (SD = 0.4). An examination of formulation effects showed a significantly greater rate of change over time in the Oral group with a weight increase of approximately 11.0 kg (SD = 8.2) or 3.5 BMI (SD = 0.7, compared to the LAI group with a gain of 3.7 kg (SD = 2.1) or 0.8 BMI (SD = 0.1) in the LAI group. These differences could not be explained by demographic or clinical characteristics, medication dosage, or baseline weight. CONCLUSIONS: While aripiprazole is generally considered relatively benign in terms of weight, it still poses a significant risk especially for people with early psychosis. However the current study suggests that the risk may be lower in those treated with LAI than with Oral formulation, consolidating the clinical utility of LAI.

Implementing telepsychiatry in an early psychosis service during COVID-19: Experiences of young people and clinicians and changes in service utilization.

AIM: In response to the COVID-19 pandemic, our early psychosis program rapidly transitioned to telepsychiatry. This study examined the change in health service utilization and experiences of young people and clinicians in response to the implementation of telepsychiatry. METHODS: Mixed methodology and triangulation of evidence drawn from health service databases and survey data. Using a retrospective observational design, health service data from pre- (Time 1) and post-(Time 2) telepsychiatry periods were compared. Surveys were also conducted with representation from clinicians and young people. RESULTS: The number of appointments increased between Time 1 and 2, although this was accompanied by a near-doubling in missed appointments (8% to 13%). Young people had mixed views about telepsychiatry. While convenience was a frequently cited benefit, clients reported technological issues, isolation and lack of human connection. A preference for face-to-face appointments was linked to younger age and anxiety when using telepsychiatry. Clinicians reported improved workplace satisfaction and efficiency but noted some limitations in the use of telepsychiatry including difficulty interviewing and managing unwell clients remotely and called for greater skill development. CONCLUSIONS: The introduction of telepsychiatry in response to COVID-19 was associated with an increase in service activity; however, there was an increase missed appointments by young people. Although clinicians and clients reported positive experiences, telepsychiatry was not completely endorsed as a replacement for face-to-face interactions.

Clozapine Therapy and COVID-19: A Systematic Review of the Prevalence Rates, Health Outcomes, Hematological Markers, and Patient Perspectives.

BACKGROUND/OBJECTIVES: There have been concerns that clozapine treatment may undermine the capacity of the body to fight infection and increase the vulnerability to contracting COVID-19. This review of recent cohort studies investigated (1) whether people with a severe psychiatric disorder are at increased risk of COVID-19 and complications, (2) the immunological response of clozapine-users who contract COVID-19, and (3) patients' perspectives on COVID-19 and the pandemic response. METHODS: A systematic search of EMBASE, Medline, Pubmed, and PsycINFO databases using PRISMA guidelines using "COVID-19", "clozapine", and "vaccination" terms. RESULTS: 18 studies (out of 330 identified) met all criteria (N = 119 054 including 8045 on clozapine). There was no strong evidence that clozapine users may be at increased risk of contracting COVID-19 or developing complications after adjusting for medical comorbidities. Hematological studies showed temporary reductions in neutrophils in COVID-19-positive patients and vaccination suggesting a clozapine effect in defence against infection. Vaccination studies did not report major adverse effects. Increased plasma levels of clozapine and neutropenia however point to COVID-19-related interference of clozapine metabolism. Patient surveys reported limited impact on mental health and positive attitudes regarding pandemic response. CONCLUSION: This review did not find compelling evidence that the immune system of clozapine users put them at risk of COVID-19 and further complications. Evidence of drug-infection interactions however points to the importance of adhering to consensus guidelines about clozapine therapy during the pandemic. More evidence using longitudinal designs is required to examine the longer-term effects of COVID-19 and vaccination in this vulnerable population.

Aripiprazole in young people with early psychosis: a systematic review and meta-analysis of weight gain.

OBJECTIVE: Aripiprazole is often prescribed to young people, although there remain unanswered questions about its effects on weight gain. This study undertook a meta-analysis of weight gain occurring in young people with early psychosis who were prescribed aripiprazole. METHOD: A systematic search was conducted for studies reporting on aripiprazole and weight change in young people with a psychotic disorder. A meta-analysis integrated the data into an estimate of effect size. RESULTS: Eleven studies met the inclusion criteria amounting to 886 participants (mean age 18 years). The results showed significant weight gain averaging 2.7 kg. These increases were associated with a longer duration of exposure to aripiprazole but not a higher dosage. CONCLUSIONS: The results highlight the importance of regular patient monitoring and the early implementation of interventions to manage antipsychotic-related weight gain.

Demographic and clinical characteristics of patients who recommence clozapine following therapy interruptions.

OBJECTIVE: The proportion of patients who recommence clozapine after cessation, the time taken to resume clozapine post-cessation, and distinguishing demographic and clinical characteristics of this group have been poorly researched. We evaluated these in the current study. METHOD: We retrospectively extracted selected demographic and clinical variables and clozapine treatment interruption and recommencement data up to December 2018 of a cohort of 458 patients who first commenced clozapine between 2006 and 2016. The study was conducted at three Australian health services. RESULTS: Of the 310 (69%) patients who had at least one interruption of clozapine treatment, 170 (54.8%) did not resume clozapine, and 140 (45.2%) recommenced it after the first interruption. More than half of those who recommenced did so within a month and 80% by 12 months. Cox regression analysis revealed that age was significantly associated with recommencement, with a 2% decrease in the likelihood of restarting after an interruption for each year later that clozapine was initially commenced (HR = 0.98 95%CI: 0.97, 0.997, p = 0.02). Those who ceased clozapine due to adverse effects were less likely to restart than those who ceased due to noncompliance (HR = 0.63 95%CI: 0.41, 0.97, p = 0.03). More time on clozapine prior to interruption increased the likelihood of restarting it, with each additional month on clozapine increasing this likelihood by 1% (HR = 1.01 95%CI: 1.01, 1.02, p < 0.001). CONCLUSION: If the distinguishing demographic and clinical characteristics of the group identified in this study are corroborated through further research, this could further validate the need to identify treatment resistance and commence clozapine early in people with schizophrenia and provide appropriate interventions to those more at risk of permanent discontinuation of clozapine.

Mental health recovery and physical health outcomes in psychotic illness: Longitudinal data from the Western Australian survey of high impact psychosis catchments.

OBJECTIVE: There is a dearth of longitudinal data on outcomes in prevalent cases of psychotic illness across a range of ages and levels of chronicity. Our aim was to describe changes over time in mental and physical health outcomes, as well as patterns of service utilisation that may have influenced outcomes, in a representative prevalence sample of 641 Western Australians with a psychotic illness who, at Wave 1, were part of the National Survey of High Impact Psychosis. METHODS: In Wave 1 (2010, 2012), a two-phase design was employed to ensure representativeness: Phase 1 psychosis screening took place in public mental health and non-government organisation services, while, in Phase 2, a randomised sample was interviewed. In Wave 2, 380/641 (59%) of participants were re-interviewed, with interviews staggered between 2013 and 2016 (follow-up time: 2.3-5.6 years). Data collection covered mental and physical health, functioning, cognition, social circumstances and service utilisation. Mental health outcomes were categorised as symptomatic, functional and personal recovery. Physical health outcomes covered metabolic syndrome and its component criteria. RESULTS: In mental health, there were encouraging improvements in symptom profiles, variable change in functional recovery and some positive findings for personal recovery, but not quality of life. Participants ranked physical health second among challenges. Metabolic syndrome had increased significantly. While treatment for underlying cardiovascular risk conditions had improved, rates of intervention were still very low. More people were accessing general practices and more frequently, but there were sharp and significant declines in access to community rehabilitation, psychosocial interventions and case management. CONCLUSION: Although we observed some positive outcomes over time, the sharp decline in access to evidence-based interventions such as community rehabilitation, psychosocial interventions and case management is of great concern and augurs poorly for recovery-oriented practice. Changes in service utilisation appear to have influenced the patterns found.

Weight gain and metabolic screening in young people with early psychosis on long acting injectable antipsychotic medication (aripiprazole vs paliperidone).

AIM: Long-acting injectable (LAI)antipsychotics are often used in psychosis to assist with medication compliance and relapse prevention, although the weight gain and metabolic effects in young people are yet to be examined. This study examined the long-term effects of aripiprazole and paliperidone in LAI formulation on weight gain and metabolic parameters in young people with early episode psychosis. METHODS: Weight gain and other metabolic effects of aripiprazole and paliperidone in LAI formulation were examined in 59 young people with early episode psychosis over a 12-month period. Changes in outcome measurements were examined at baseline and 3 monthly intervals. RESULTS: The results showed that both aripiprazole and paliperidone were associated with time-dependent increases in weight. At 12 months, weight increased by an average of 7% (6 kg) with both aripiprazole and paliperidone relative to the baseline, and the percentage of overweight or obese people increased from 33% to 60%. There was no advantage of aripiprazole compared to paliperidone with regards to weight change, although aripiprazole was associated with lower triglycerides and prolactin levels. CONCLUSIONS: Both LAI medications were associated with substantial weight increases over time. These results build on emerging evidence showing that aripiprazole is not weight neutral in young people. Our recommendation is that weight-management programs should be offered from the start of medication initiation.