Nuedexta in Treatment-Resistant Major Depression

Inclusion Criteria:

• Male or female participants, 18-65 years of age;

• Current primary Axis I diagnosis of major depressive disorder according to DSM-IV-TRcriteria as determined by a psychiatrist and confirmed with the Structured ClinicalInterview for DSM-IV Axis I Disorders (SCID);

• Current treatment-resistant depression defined by a history of inadequate response toa minimum of 2 adequate antidepressant treatment trials determined by patient historyand chart review and confirmed with the Antidepressant Treatment History Form (ATHF);

• Participants must be willing to discontinue treatment with concomitant medicationsthat are disallowed by the study protocol;

• Participants must have a level of understanding of the English language sufficient toagree to all tests and examinations required by the study and must be able toparticipate fully in the informed consent process.

Exclusion Criteria:

• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder,pervasive developmental disorders or mental retardation

• Diagnosis of a substance use disorder within the past 1 year ;

• Female participants who are pregnant, nursing, for may become pregnant;

• Any unstable medical illnesses including hepatic, renal, gastroenterologic,respiratory, cardiovascular (including ischemic heart disease); endocrinologic,neurologic (including history of severe head injury), immunologic, or hematologicdisease;

• Participants with clinically significant abnormalities of laboratories, physicalexamination, or ECG;

• Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades depointes, or heart failure;

• Complete atrioventricular (AV) block without implanted pacemaker, or patients at highrisk of complete AV block

• Participants with a history of quinidine, quinine or mefloquine-inducedthrombocytopenia, hepatitis, or other hypersensitivity reactions;

• Participants judged to be at serious suicidal risk by the PI;

• Concomitant use with quinidine, quinine, or mefloquine;

• Participants with known hypersensitivity to dextromethorphan;

• Use with an MAOI or within 14 days of stopping an MAOI;

• Concomitant use with drugs that prolong QT interval and are metabolized by CYP2D6