NRX-101 for Bipolar Depression With Subacute Suicidal Ideation

Background and Rationale: NMDA antagonist drugs have shown to reduce symptoms of depression and suicidal ideation. NRX-101 is composed of D-cycloserine (DCS) an NMDA antagonist and lurasidone (5HT2a atypical antipsychotic and antidepressant). In a phase 2 clinical study of bipolar depression and acute suicidal ideation and behavior, (in patients requiring hospitalization) patients received an initial infusion of ketamine and then NRX-101 for 6 weeks. In that phase 2 study, NRX-101 showed the ability to maintain remission from depression and suicidality over 6 weeks when taken twice daily. In this current out patient study, patients with bipolar depression and subacute suicidality (not requiring hospitalization), ketamine will not be used. Primary Objective: * To test the hypothesis that treatment with NRX-101 is superior to standard of care (lurasidone) in improving symptoms of depression as measured by the total Montgomery Åsberg Depression Rating Scale (MADRS-10) score in patients with bipolar depression and subacute suicidal ideation and behavior (SSIB) which does not require hospitalization. Secondary Objectives: • To test the hypothesis that treatment with NRX-101 is superior to standard of care (lurasidone) in reducing suicidality in depressed bipolar patients with SSIB, as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) Methodology: : A multi-center, randomized, double-blind, trial in which patients with bipolar depression (MADRS ≥30) and subacute levels of suicidal ideation (C-SSRS 3 or 4, not requiring hospitalization) are randomized to receive twice daily oral NRX-101 or lurasidone (standard of care).