The safety and effectiveness of long-acting injectable antipsychotics versus oral antipsychotics among people with schizophrenia

Abstract

Antipsychotics serve as the primary pharmacological treatment for schizophrenia. However, nonadherence to medication poses a significant challenge in managing the condition, primarily due to insufficient support and cognitive impairment. In comparison to oral antipsychotics (OAs), which necessitate daily intake, long-acting injectable antipsychotics (LAIAs) were developed to enhance patient adherence by extending the dosing intervals. Nevertheless, the utilisation of LAIAs remains low due to various barriers, including concerns about side effects and uncertainties regarding long-term effectiveness. Nonadherence is particularly problematic among specific patient groups, such as older individuals and those with comorbid substance use disorders (SUD). However, the use of LAIAs in these groups has not been systematically investigated. Furthermore, there is limited knowledge regarding the effectiveness and safety of using LAIAs as an augmentation strategy for clozapine treatment. To address the aforementioned knowledge gaps, this thesis aimed to achieve three main objectives: (1) to evaluate the long-term effectiveness and safety of LAIAs compared to OAs among the general population with schizophrenia, (2) to assess the effectiveness and safety of LAIAs compared to OAs among special patient groups, such as older individuals and those with comorbid SUD, who are at a high risk of nonadherence, and (3) to examine the effectiveness and safety of the combination use of clozapine and LAIAs. The studies conducted in this thesis utilised electronic medical records from public hospitals in Hong Kong and employed within-individual comparisons. The key findings of the thesis were as follows: (1) LAIAs demonstrated superior effectiveness and tolerability when compared to OAs among the general population with schizophrenia. This positive association persisted throughout subsequent treatment periods, and LAIAs led to improved treatment outcomes across all stages of the illness, particularly when initiated earlier. (2) Among older individuals with schizophrenia, LAIAs were generally safe and effective, although careful monitoring for extrapyramidal symptoms was necessary when initiating LAIAs in this population. Among people with comorbid SUD, the use of LAIAs was highly recommended because it was associated with a lower risk of hospitalisation for both schizophrenia and SUD. (3) However, the current evidence did not support the combination use of clozapine and LAIAs. This research is the first to systematically investigate the effectiveness and safety of LAIAs in individuals with schizophrenia within the Asian population, as well as among special patient groups, including those in the early course of illness, older individuals, and those with comorbid SUD. Additionally, this study provides novel insights into the effectiveness and safety of the combination use of clozapine and LAIAs. Overall, the findings of this thesis suggest that LAIAs are associated with superior effectiveness and safety compared to OAs and should be recommended for individuals with schizophrenia, particularly during the early stages of illness. The findings also support the use of LAIAs among older individuals and those with comorbid SUD. However, the combination use of clozapine and LAIAs lacks sufficient support from the current evidence, and the decision to prescribe this treatment combination should involve a careful assessment of the potential benefits and risks in clinical practice.