T-CIDDeveloping Improved Treatment for Cognitive Impairment in Depression

Vortioxetine is the only FDA approved medication for treating cognitive impairment in depression. This medication, however, takes a minimum of 6-8 weeks to take effect and is only effective in a subset of patients. Modafinil, has shown some benefit in off-label treatment of cognitive dysfunction in psychiatric disorders. The effects of modafinil on cognitive function in both healthy controls and treatment resistant and partially remitted individuals with MDD have shown promising results. To date, however, studies have focused on modafinil's potential as an augmenting agent for treatment resistant depressive symptoms, but have not examined its effects on cognitive function in depression as a primary outcome measure. Modafinil's ability to treat cognitive symptoms in non-treatment refractory or partially remitted individuals specifically struggling with cognitive impairment resulting from MDD have not been assessed. Further, we lack a mechanistic understanding of modafinil's effects on brain circuitry. The proposed research seeks to examine the effects of modafinil on different domains of cognitive function such as attention, working memory and processing speed, as well as its underlying effects on brain circuitry in individuals who demonstrate cognitive impairment and meet criteria for first episode of major depressive disorder. Specifically, this study would examine the effect of administering low dose modafinil, a drug that has been used off-label to treat cognitive dysfunction in psychiatric disorders, on cognitive function in major depressive disorder in a two-session double-blind, randomized, placebo-controlled design. The primary aim of the study is to examine the effect of modafinil on domains of cognitive processing and function in depression as well as the neural mechanisms underlying its effects using functional magnetic resonance imaging (fMRI). A secondary aim of this study is to compare the efficacy of modafinil in treating cognitive dysfunction to that of vortioxetine in an optional phase 2 open-label follow up. In an optional second phase of the study, participants randomized to the placebo group, will have the option of enrolling in an open label trial of either modafinil or vortioxetine, the only currently FDA approved medication to treat cognitive impairment in depression. Study findings may provide the foundations for future work focused on treating cognitive impairment in depression.