Eligible participants included men and women, ages 18 to 65 years. Subjects with MDD had been diagnosed with recurrent MDD without psychotic features using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID)-Patient Version (40 ). Subjects were required to have a score ≥20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) at screening and before each infusion. Subjects had to have not responded to at least one adequate antidepressant trial during their current episode, as assessed using the Antidepressant Treatment History Form (41 ), and the current episode had to have lasted at least four weeks. Subjects were free from psychotropic medications in the two weeks before randomization (five weeks for fluoxetine, three weeks for aripiprazole). A patient sample size of 34 individuals was necessary to have 80% power to detect an antidepressant effect of ketamine (d=0.5) with p<0.05, two-tailed.
Healthy control subjects consisted of males and females, 18–65 years old with no Axis I disorder as determined by SCID-NP, and no family history of Axis I disorders in first degree relatives. Healthy control subjects were free of medications affecting neuronal function or cerebral blood flow or metabolism. Subjects in both groups were in good physical health as determined by medical history, physical exam, blood labs, electrocardiogram, chest x-ray, urinalysis, and toxicology. The study was approved by the National Institutes of Health (NIH) Combined Neuroscience Institutional Review Board. All subjects provided written informed consent before entry into the study (NCT00088699).