Grant: Project Grant

Bipolar disorder (BD) is a mental health condition characterized by extreme shifts between mania and depression. BD is associated with an earlier death, often caused by cardiovascular disease. In our recent studies we have found that people with BD who also have insulin resistance (IR), a condition where your body does not respond normally to insulin, are more likely to have worse depression, and are less likely to respond to mood stabilizers. The biological reason for this link between poorer insulin regulation and BD is not well understood. We know that IR in the brain can disrupt how the brain regulates mood. We have shown that patients with both BD and IR have more severe depression, and poorer functioning. A recent study by some of our team has shown that reversal of IR during treatment with metformin, a medication used to control high blood sugar, results in improvement of depressive symptoms and function in BD. The aim of our study is to reproduce the finding that treating IR with metformin will result in improved depressive symptoms in BD. We expect that individuals who have IR reversal with metformin will experience greater improvement in mood and better function and cognition than those who did not have IR reversal. This study will include 194 participants with BD taking up to 2000 mg of metformin or placebo (no active medication) daily for 14 weeks and measurement of changes in depressive symptoms, functioning, and cognition. This clinical trial will provide a new avenue for treatment and greater understanding of the biology behind BD.