Grant: CIHR Fellowship

Individuals with schizophrenia spectrum disorders (SSDs) experience high rates of metabolic disturbances such as diabetes and obesity. This is worsened by antipsychotics (APs), the cornerstone treatment for SSDs, which are associated with severe weight gain. As a result, this population experiences poorer symptoms, as obesity is closely linked with an increased risk for suicidality. Despite this, metabolic comorbidities remain undertreated and first-line treatments for weight loss in SSDs, such as metformin, are effective in less than a quarter of patients. The emergence of pharmacological candidates such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RAs), reflects a shift in the use of effective antidiabetic agents for additional benefits for weight loss. Conversely, recent investigations by regulatory agencies have reported a relationship between GLP-1RAs and suicidality. Given the increasing use of GLP-1RAs, it is crucial to understand their implications on suicidality, which remains underexplored in the context of SSDs. Therefore, this study aims to explore whether semaglutide is associated with suicidality in overweight/obese individuals with SSD, and whether the association is mediated by changes to weight or insulin resistance (IR) while on the study drug. Data will be collected from an ongoing randomized controlled trial (NCT05333003) where overweight/obese individuals with SSD will receive either semaglutide or placebo (no active ingredients) for 32 weeks. The Calgary Depression Scale for Schizophrenia (CDSS) will be used to assess suicidality at baseline, midpoint (16 weeks), and endpoint (32 weeks). Scores collected pre and post trial will be compared between intervention groups, and assessed in relation to changes in weight and IR while on the study drug. Examining the effect of semaglutide on suicidality may determine the safety of the intervention and has the potential to improve outcomes in an area of significant unmet need.