Glucose biomarkers and antidepressant response: A scoping review of interventions targeting major depressive disorder...

Growing evidence implicates glucose dysregulation in the pathophysiology of Major Depressive Disorder (MDD), and metabolic markers have been linked to antidepressant treatment outcomes. This scoping review comprehensively investigates associations between glucose-related biomarkers (e.g., HbA1c, fasting glucose, insulin) and antidepressant response across interventions targeting either metabolic dysfunction or depressive symptoms.

A systematic search of three databases in December 2024 and a supplementary manual search of reference lists was conducted in September 2025 and yielded 78 eligible studies encompassing 32,434 participants. Included studies assessed the impact of interventions such as antidepressant medications, behavioural therapies, diabetes-specific treatments, and neuromodulation on both mood and metabolic outcomes. Randomized controlled trials were the most common study design. The study was registered prospectively in Open Science Framework.

Reductions in glucose biomarkers, particularly HbA1c, were often reported alongside improvements in depressive symptoms among individuals with and without comorbid diabetes. Both pharmacological (n = 37) and behavioural (n = 25) interventions were described as showing concurrent effects on mood and metabolic parameters. In contrast, diabetes-specific treatments (n = 12) demonstrated more variable effects on depression. Only four studies on neuromodulation were identified, with mixed findings regarding glucose biomarkers.

This review contributes to the growing body of work in metabolic psychiatry by highlighting the interconnection between glucose regulation and antidepressant response to pharmacotherapy, psychotherapy and behavioural interventions. These findings emphasize the need for targeted research into glucose biomarkers as potential indicators of treatment outcomes and in relation to neuromodulation treatment outcomes.