¹University of Queensland, Faculty of Medicine, Brisbane, Australia

Background: Schizophrenia affects 1% of the global population, with one-third experiencing treatment-resistant schizophrenia (TRS). Clozapine is the most effective treatment for TRS, yet 60% of patients fail to achieve adequate response. Augmentation strategies are often limited. Adaptive platform trials, used successfully in other areas like COVID-19, offer a novel method to efficiently evaluate multiple augmentations strategies for TRS. Cannabidiol (CBD) has shown promise in reducing positive symptoms but remains untested in clozapine-resistant patients.

Aims & Objectives: To evaluate the efficacy of CBD and other augmentation strategies in clozapine-resistant schizophrenia through an adaptive platform trial.

Method: By using a Master Protocol and adaptive platform trial architecture will assess multiple interventions for psychosis symptoms among people with TRS. Adaptive randomisation and Bayesian analysis will be used to optimize trial efficiency.
The first randomisation will be of cannabidiol. We will conduct a 12-week, randomized, double-blind trial will test CBD (1,000 mg daily) in 88 individuals with clozapine-resistant schizophrenia. The primary outcome is change in positive PANSS scores; secondary outcomes include total and negative PANSS, sleep, anxiety, cognitive functioning, and metabolic health.

Results: We will present the results of the interim analysis of CBD versus placebo for clozapine resistant schizophrenia

Discussion & Conclusions: CBD may offer a promising augmentation for clozapine-resistant schizophrenia. The adaptive platform trial design improves trial efficiency, providing patients quicker access to effective treatments through real-time assessments and adjustments.