Clinical trial NCT01882829: Nuedexta in Treatment-Resistant Major Depression
Official title: Targeting the NMDA Glutamate Receptor as Novel Antidepressant Strategy: A Pilot Clinical Trial of Nuedexta in Treatment-Resistant Major Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Treatment Resistant
Keywords: depression
major depressive disorder
treatment resistant
Nuedexta
dextromethorphan
antidepressant
glutamate
NMDA receptor
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2013-06-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: At baseline and visit 6 (week 10)
Secondary outcomes:
measure: Quality of Life Enjoyment and Satisfaction Questionnaire Short Form
timeFrame: At baseline and Visit 6 (week 10)
measure: Range of Impaired Functioning Tool
timeFrame: At baseline and Visit 6 (week 10)
measure: Sheehan Disability Scale
timeFrame: At baseline and Visit 6 (week 10)
measure: Patient Rated Inventory of Side Effects (PRISE)
timeFrame: up to 12 weeks
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: up to 12 weeks
measure: Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)
timeFrame: up to 12 weeks
measure: Clinical Global Impression (CGI) Scale
timeFrame: up to 12 weeks
measure: Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
timeFrame: At baseline and Visit 6 (week 10)
measure: HAM-A
timeFrame: Baseline and Week 10
measure: Beck Scale for Suicidal Ideation (BSI)
timeFrame: Baseline and Week 10
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James Murrough, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.