The use of clozapine in a rural and remote region of Australia

Abstract

Objective: Clozapine is the most effective antipsychotic available for treatment-resistant schizophrenia. Unfortunately, it is often underutilised or administered late in the treatment course, if at all. This issue is further augmented in rural and remote regions where access to treatment is sparse. This study is the first of its kind to investigate the use of clozapine in a remote and regional area of Australia with a high proportion of Aboriginal and/or Torres Strait Islander individuals. Methods: This study includes all individuals who were commenced on clozapine between June 2013 and June 2018. Relevant clinical information was sourced from electronic medical records and descriptive statistical analysis performed. Results: A total of 3850 patients with psychotic disorders were reviewed over 5 years, of whom 63 were commenced on clozapine. The majority were male ( n = 50, 79.4%) with a mean age of 33.9 years (standard deviation 11.0). A total of 34.9% ( n = 22) identified as Aboriginal and/or Torres Strait Islander. The mean length of time between diagnosis and commencement of clozapine was 7.2 years (standard deviation ±4.6 years), while the mean number of antipsychotic medications tried prior to clozapine was 4.2 (standard deviation ±1.6 antipsychotics). Clozapine was discontinued in 57.1% of the individuals in this study (41% within the first 12 months). The most common cause for cessation was poor compliance ( n = 19, 30.2%). Conclusion: While clozapine remains the most effective antipsychotic treatment, it is often commenced late in the treatment or ceased prematurely. Further work is required, particularly in remote and regional populations, to ensure treatment adherence for optimal patient outcomes.

Rates and Reasons for Clozapine Treatment Interruptions

“…We also observed that 16 patients (17.4% of adverse effects) in our cohort ceased clozapine because of myocarditis. Similarly, Thien et al 24 and Bridson et al, 21 studying relatively small samples of early psychosis and patients residing in remote areas in Australia, observed that the major reason (approximately 60%) for discontinuation due to adverse effects could be attributed to cardiac causes. However, most researchers from Europe and United States have reported that hematological (neutropenia or agranulocytosis) and central nervous system (sedation and seizures) issues comprised the majority of the adverse effects which warranted cessation of clozapine.…”

“…The incidence of all-cause therapy interruption of 70% observed in our cohort of 457 patients is at the higher end of the figures reported in the literature. A range of discontinuation rates of clozapine has been reported by various authors, with some reporting figures of more than 50%, 9,10,21 while others have found rates in the low 20s 12,17 . Several factors such as sampling variations, the length of the follow-up period, definition and determination of treatment interruption/discontinuation, and differences in sociodemographic, geographic, clinical, and health service factors related to the population researched could account for some of the discrepancies.…”

“…Despite our cohort being followed up for a minimum of 2 years and a median duration of 7 years, a significant proportion (41%) of those who had an interruption in our study had it within the first 18 weeks after commencing clozapine, which is the period of the mandatory weekly hematological monitoring. Many authors have reported a higher discontinuation rate in the initial year of treatment with clozapine 9,10,21,25 . Some researchers have observed that a significant proportion of discontinuation of clozapine, ranging from 8% to 21%, is related to the requirement of hematological monitoring 14,16,17,25 .…”

“…Treatment with clozapine could confer added benefits by reducing the risk of aggression, 5 mortality, 6 substance abuse, 7 and hospitalization in people with schizophrenia 8 . However, interruptions and discontinuation of clozapine treatment are common in clinical practice, and various authors have reported rates ranging from 20% to 60% 9–25 . Older age, African-American and African-Caribbean background, substance abuse, living in deprived areas, and male sex were found to be associated with clozapine discontinuation by some researchers 10,11,13,14,16–18 …”