Subnormal level of Glutamate+Glutamine (Glx) in the Anterior Cingulate Cortex (ACC) of the
brain has been associated with depression and PTSD. Similarly, interventions that increase
the level of Glx in the brain, specifically electroconvulsive therapy (ECT) and intravenous
ketamine infusion have been associated with a rapid decrease in depression and suicidal
ideation. This effect has been demonstrated in a dose-dependent manner in randomized clinical
assessments. D-cycloserine, a glycine site modulator of NMDA receptor function has been
demonstrated to increase Glx in the ACC of normal volunteers. The purpose of this study is to
determine whether NRX-101, an experimental drug containing a fixed dose combination of
D-cycloserine and lurasidone (1) raises Glx by a greater amount than either placebo or
lurasidone alone in patients with bipolar depression, and (2) whether that elevation in Glx
is correlated with a decrease in depression.