NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder

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