Method of treating major depressive disorder

A method of treating major depressive disorder in a human patient in need thereof consisting essentially thereof orally administering once daily to said patient over a treatment regimen of at least 28 days, an oral dosage form consisting of esketamine and a pharmaceutical carrier, wherein the ratio of S-norketamine Cmax to esketamine Cmax after the administration of the esketamine is at least 6, and

• wherein said oral esketamine dosage form administration provides for
• i. an (2S,6S)-OH-norketamine Cmax of between 15 and 75 ng/ml;
• ii. an (2S,6S)-OH-norketamine AUC0-t of between 105 and 850 ng*h/ml;
• or
• iii. an (2S,6S)-OH-norketamine Cmax of between 15 and 75 ng/ml and an (2S,6S)-OH-norketamine AUC0-t of between 105 and 850 ng*h/ml
• and optionally administering to the patient a second medication that is an antidepressant, an antimanic agent or an anxiolytic drug that does not alter the metabolism of the esketamine in the patient.