Effectiveness and Heterogeneity of Multimodal Interventions for Mood and Anxiety Outcomes in Insulin-Resistant Populations: A Systematic Review of Randomized Controlled Trials

Introduction: Insulin Resistance (IR) is a prevalent metabolic condition affecting approximately 26.5% of adults globally and is increasingly recognised for its association with mood and anxiety disorders. This systematic review synthesises evidence from randomised controlled trials (RCTs) to evaluate the effectiveness and heterogeneity of multimodal interventions targeting mental health outcomes in insulin-resistant populations. Method A systematic search on PubMed and MEDLINE identified 1,848 records, of which 42 RCTs (N = 14,982 participants) met inclusion criteria. Included studies examined diverse interventions, including pharmacological, psychological, lifestyle, and integrated care approaches across populations with conditions such as type 2 diabetes, metabolic syndrome, and polycystic ovary syndrome. Results Across studies, interventions consistently demonstrated significant within-group improvements in depressive symptoms, with moderate-to-large effect sizes reported in several trials. Anxiety outcomes also showed reductions, although findings were more variable. However, between-group differences relative to control conditions were less consistent across studies. Bipolar disorder was minimally represented, limiting conclusions for this subgroup. Conclusion Overall, while interventions appear effective in improving mood outcomes within insulin-resistant populations, substantial heterogeneity and inconsistent comparative efficacy limit definitive conclusions. Future research should prioritise standardised outcome measures, longitudinal designs, and broader psychiatric inclusion to improve clinical and public health relevance.