Original Research J Clin Psychiatry February 2022

Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study): A Randomized, Quadruple-Masked, Placebo-Controlled Clinical Trial

JCP 2022;83(2):10.4088/JCP.21m14022

Full Article Read the complete peer-reviewed article in J Clin Psychiatry. Clinical Summary Patients with treatment-resistant bipolar depression often remain depressed despite multiple adequate medication trials, with high functional burden and few evidence-based next steps. This trial asks a clinically practical question: if insulin resistance is driving a subset of refractory bipolar depression, can reversing it with metformin improve depressive symptoms, anxiety, and functioning? FAQ Did metformin improve outcomes in treatment-resistant bipolar depression?

Key Takeaways In this highly refractory cohort, the metabolic target identified a clinically meaningful subgroup: 91.2% had failed drug trials from at least 3 psychotropic drug classes, 55.6% had failed drugs from all 4 drug classes, and mean lifetime failed medication trials for bipolar disorder was 8.6. Clinical Guide How should clinicians identify patients with treatment-resistant bipolar depression who may be candidates for insulin resistance-targeted treatment? Clinical Guide How should clinicians conduct a metformin trial for patients with insulin-resistant treatment-resistant bipolar depression based on the TRIO-BD study?