Treatment-Resistant Depression Outpatient Study

Patients were treated as outpatients with ages from 22 to 69 years who signed an informed consent form and had HDRS-21 ≥ 20 that was stable between screening and baseline assessments (±30%; Figure 1). Only patients who did not respond in the current episode to at least 1 and up to 4 antidepressant drug trials were eligible for this study (further details on inclusion and exclusion criteria are provided in the Supplemental Methods). Main exclusion criteria included comorbid psychiatric and neurological disorders, presence of psychosis, primary anxiety disorder causing higher distress than MDD, substance abuse within 6 months, prominent personality disorder causing higher distress than MDD, dysthymia, prior head trauma or seizures, and suicide attempt within 3 years. Mood stabilizers and antipsychotics were not allowed. Antidepressants were allowed but had to be maintained at a stable dose for at least 2 months before enrollment and throughout the study.