Nuedexta in Treatment-Resistant Major Depression

James Murrough20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Major Depressive Disorder Treatment Resistant

Interventions

dextromethorphan/quinidineDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Outcomes

Primary Outcomes

Montgomery-Asberg Depression Rating Scale

The Montgomery-Asberg Depression Rating Scale is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is s scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Primary outcome is change in MADRS at Visit 6 (Week 10). Higher values represent a worse outcome.

Time frame: At baseline and visit 6 (week 10)

Secondary Outcomes

Quality of Life Enjoyment and Satisfaction Questionnaire Short Form

The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form is a reliable and valid self-report measure designed to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by individuals. The raw total score ranges from 14 to 70. Higher scores reflect better oucomes.

Time frame: At baseline and Visit 6 (week 10)

Range of Impaired Functioning Tool

The Range of Impaired Functioning Tool a brief scale for assessing functional impairment related to medical or psychiatric illness and has been demonstrated to possess good psychometric properties. The LIFE-RIFT has a total score and individual domain scores for the following areas of functioning: household duties, work, recreation, relationships with family, relationships with friends, schoolwork, and global life satisfaction (the satisfaction item is patient rated). Higher scores indicate poorer functioning; scores ≥2 reflect impaired functioning in that domain. Results are reported for the total sum with full range from 3 (no impairment) to 60 (severe impairment), which is based on all individual domain scores.

Time frame: At baseline and Visit 6 (week 10)

Sheehan Disability Scale

The Sheehan Disability Scale (SDS) is a self-rated scale which assesses illness-related disability in three areas of functioning: work, social and family. The SDS assess disability or functional impairment across three domains: work/school, social life/leisure activities and family life/home responsibilities. Each domain is scored from 0 (not at all) to 10 (very severely). The three domains can be summarized to evaluate global functional impairment by adding the scores of each of the three domains, resulting in global SDS score ranges from 0 (unimpaired) to 30 (highly impaired).

Data from ClinicalTrials.gov

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