NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder

Phase 2RecruitingNCT05136755

China Medical University Hospital50 enrolled

Overview

Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of antidepressant nonresponders with MDD.

Major depressive disorder (MDD) is a multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many patients respond poorly to antidepressants and suffer from side effects. NMDA hypofunction has been implicated in the pathophysiology of depression. MDD is often associated with cognitive deficits which are not necessarily recovered by current antidepressants. The NMDA receptor regulates synaptic plasticity, memory, and cognition. Therefore, this study aims to examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of antidepressant nonresponders with MDD. The investigators will enroll a total of 50 antidepressant nonresponders with MDD. All patients, continuing their originally ongoing treatment throughout the study period, will be randomly assigned into either of two treatment groups: NMDAE or placebo. We will biweekly measure clinical performances using 17-item Hamilton Rating Scale for Depression, Global Assessment of Function, Perceived Stress Scale, Visual Analogue Scale for pain, Clinical Global Impression, and side effects. Quality of life and cognitive functions will be assessed at baseline and at endpoint of treatment. The efficacies of NMDAE and placebo will be compared. Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Major Depressive Disorder

Interventions

NMDAEDRUG

Use of an NMDA enhancer for the treatment of antidepressant nonresponders with MDD

Placebo CapDRUG

Use of placebo as a comparator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have a DSM-5 (American Psychiatric Association) diagnosis of MDD * Have failed to respond to at least one antidepressant with adequate dosage and treatment duration * Their original treatments should have been unchanged for at least 8 weeks. Some treatment-resistant patients (that is, having failed to respond to at least two different classes of antidepressants) who have started to refuse any antidepressant by themselves due to previous failure experience are also allowed, if they have already been antidepressant-free for at least 2 weeks * 17-item Hamilton Rating Scale for Depression total score ≥ 18 * Agree to participate in the study and provide informed consent Exclusion Criteria: * Current substance abuse or history of substance dependence in the past 6 months * History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study * Bipolar disorder, schizophrenia or other psychotic disorder * Moderate-severe suicidal risks * Severe cognitive impairment * Initiating or stopping formal psychotherapy within six weeks prior to enrollment * A history of previously received electroconvulsive therapy * Inability to follow protocol

Locations (1)

Department of Psychiatry, China Medical University Hospital

Taichung, Taiwan

RECRUITING

Outcomes

Primary Outcomes

Change in Hamilton Rating Scale for Depression

Assessment of depressive symptoms Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.

Time frame: week 0, 2, 4, 6, 8

Change in Global Assessment of Functioning

Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.

Time frame: Week 0, 2, 4, 6, 8

Secondary Outcomes

Change Change in Perceived Stress Scalein Perceived Stress Scale

Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.

Time frame: week 0, 2, 4, 6, 8

Visual Analogue Scale for pain

Assessment of pain Minimum value: 0, maximum value:10, the higher scores mean a worse outcome.

Time frame: week 0, 2, 4, 6, 8

Clinical Global Impression

Time frame: week 0, 2, 4, 6, 8

Quality of life (SF-36)

Time frame: week 0, 8

Visual Continuous Performance Test

Assessment of sustained attention

Time frame: week 0, 8

Wisconsin Card Sorting Test

Assessment of abstract and shift set

Time frame: week 0, 8

Logical Memory Test of the Wechsler Memory Scale

Central Contacts

Hsien-Yuan Lane, M.D., Ph.D

CONTACT

886 4 22052121 hylane@gmail.com

Data from ClinicalTrials.gov

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