Nuedexta in Treatment-Resistant Major Depression
Condition: Major Depressive Disorder; Treatment Resistant
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: dextromethorphan/quinidine
Intervention description: up to 45/10 mg every 12 hours in patients with TRD with a short 7 day tapering period in which subjects are tapered off 45/10 mg dose from twice a day to once daily for an additional 7 days at post 8-week treatment period to minimize the potential for discontinuation effects
Intervention MeSH terms: Quinidine; Dextromethorphan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; major depressive disorder; treatment resistant; Nuedexta; dextromethorphan; antidepressant; glutamate; NMDA receptor

Summary:

      There is an urgent need, therefore, to identify well-tolerated, orally available compounds
      that target the NMDA receptor as a novel treatment approach for TRD. The current project aims
      to test the safety, tolerability and efficacy of Nuedexta - containing the NMDA antagonist
      dextromethorphan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participants, 18-65 years of age;

          -  Current primary Axis I diagnosis of major depressive disorder according to DSM-IV-TR
             criteria as determined by a psychiatrist and confirmed with the Structured Clinical
             Interview for DSM-IV Axis I Disorders (SCID);

          -  Current treatment-resistant depression defined by a history of inadequate response to
             a minimum of 2 adequate antidepressant treatment trials determined by patient history
             and chart review and confirmed with the Antidepressant Treatment History Form (ATHF);

          -  Participants must be willing to discontinue treatment with concomitant medications
             that are disallowed by the study protocol;

          -  Participants must have a level of understanding of the English language sufficient to
             agree to all tests and examinations required by the study and must be able to
             participate 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 hematologic
             disease;

          -  Participants with clinically significant abnormalities of laboratories, physical
             examination, or ECG;

          -  Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de
             pointes, or heart failure;

          -  Complete atrioventricular (AV) block without implanted pacemaker, or patients at high
             risk of complete AV block

          -  Participants with a history of quinidine, quinine or mefloquine-induced
             thrombocytopenia, 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