What does “treatment-resistant depression” in the indication for esketamine (Spravato®) mean?

By Rajnish Mago, MD (bio) Esketamine nasal spray (brand name Spravato®) was approved by the FDA in March 2019. As of January 2020, the wording in the Prescribing Information notes that it is “indicated, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults.” That’s pretty vague! I was really…