Clinical trial NCT05136755: NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder
Official title: NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Major depressive disorder
Antidepressant nonresponders
NMDA
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2021-11-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Hamilton Rating Scale for Depression
timeFrame: week 0, 2, 4, 6, 8
measure: Change in Global Assessment of Functioning
timeFrame: Week 0, 2, 4, 6, 8
Secondary outcomes:
measure: Change Change in Perceived Stress Scalein Perceived Stress Scale
timeFrame: week 0, 2, 4, 6, 8
measure: Visual Analogue Scale for pain
timeFrame: week 0, 2, 4, 6, 8
measure: Clinical Global Impression
timeFrame: week 0, 2, 4, 6, 8
measure: Quality of life (SF-36)
timeFrame: week 0, 8
measure: Visual Continuous Performance Test
timeFrame: week 0, 8
measure: Wisconsin Card Sorting Test
timeFrame: week 0, 8
measure: Logical Memory Test of the Wechsler Memory Scale
timeFrame: week 0, 8
measure: Digit Span
timeFrame: week 0, 8
measure: Spatial Span
timeFrame: week 0, 8
measure: Category Fluency
timeFrame: week 0, 8
measure: Trail Marking A
timeFrame: week 0, 8
measure: WAIS-III Digit Symbol-Coding
timeFrame: week 0, 8
measure: Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0
timeFrame: week 0, 8
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: