Nuedexta in Treatment-Resistant Major Depression

James Murrough

Status and phase

Completed

Phase 2

Conditions

Major Depressive Disorder

Treatment Resistant

Treatments

Drug: dextromethorphan/quinidine

Study type

Interventional

Funder types

Other

Identifiers

NCT01882829

IF1463152

GCO 13-0389

Details and patient eligibility

About

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.

Full description

Approximately one-third of patients with major depressive disorder do not achieve adequate symptom control despite a series of multiple treatment trials with currently available antidepressant medication (for example a serotonin-selective reuptake inhibitor). This group of patients - representing treatment-resistant depression (TRD) - accounts for an alarmingly high public health burden and signifies a critical area of need in pharmaceutical treatment development. While current treatments are slow to act and only partially effective, new basic and clinical research focusing on the glutamate system is yielding promising new avenues for novel drug discovery. Ketamine - a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist - has now been demonstrated in several studies to bring about a rapid and robust antidepressant effect, even in patients suffering from TRD. Ketamine is limited as a treatment for TRD by the need for intravenous administration and the potential for untoward medical or psychiatric adverse effects. 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.

Enrollment

20 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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