Cognitive effects of mifepristone in overweight, euthymic adults with depressive disorders

•Mifepristone improves fasting glucose levels.•Decrease in fasting glucose predicts improvement in verbal learning with mifepristone.•Decrease in fasting glucose predicts improvement in attention with mifepristone. Previous studies have shown that individuals with mood disorders have a higher prevalence of both hypercortisolemia and insulin resistance. Insulin resistance is posited to contribute to the cognitive deficits observed in individuals who have depression. However, the mechanistic relationship between cortisol and insulin within the central nervous system remains to be further elucidated. This study aimed to evaluate the effects of the antiglucocorticoid agent, mifepristone, on metabolic function and cognitive performance in individuals receiving treatment for depressive disorders who were euthymic at baseline. Participants were administered a 600 mg/day dose of mifepristone for 28 days. Oral glucose tolerance tests (OGTTs) and cognitive assessments measuring verbal memory and executive functioning were administered at baseline and after 28 days of treatment. Improvements in attention and verbal learning were associated with reduction of fasting plasma glucose (FPG) in response to mifepristone treatment. Limitations include the open-label design of this study and a small sample size. The findings from this study suggest that improvement in fasting plasma glucose levels, upon administration of mifepristone, is associated with the improvement in early input of verbal information. Further studies are warranted in order to better evaluate the use of mifepristone or other antiglucocorticoid agents in treatment of mood disorders characterized by metabolic dysfunction.