Nuedexta in Treatment-Resistant Major Depression

NCT ID: NCT01882829

Last Updated: 2018-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2016-03-31

Brief 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.

Detailed 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.

Conditions

Major Depressive Disorder; Treatment Resistant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nuedexta (dextromethorphan/quinidine)

45/10 mg every 12 hours x 8 weeks

Group Type: EXPERIMENTAL

dextromethorphan/quinidine

Intervention Type: DRUG

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

Interventions

dextromethorphan/quinidine

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 Type: DRUG

Other Intervention Names

Nuedexta

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

James Murrough

OTHER

Sponsor Role: lead

Responsible Party

James Murrough

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

James Murrough, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

Murrough JW, Wade E, Sayed S, Ahle G, Kiraly DD, Welch A, Collins KA, Soleimani L, Iosifescu DV, Charney DS. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial. J Affect Disord. 2017 Aug 15;218:277-283. doi: 10.1016/j.jad.2017.04.072. Epub 2017 Apr 29.

Reference Type: RESULT

PMID: 28478356 (View on PubMed)

Other Identifiers

IF1463152

Identifier Type: -

Identifier Source: secondary_id

GCO 13-0389

Identifier Type: -

Identifier Source: org_study_id