Despite encouraging results, questions remain, Dr. Zarate and his coauthors said. "It’s unclear why many patients showing a response at 24 hours relapse less than 48 hours later," they wrote. "It’s also unclear why some patients maintain their response for several weeks."
Although the drug’s adverse event profile is largely acceptable, "there are disadvantages to continuing patients on thrice-weekly or even weekly [intravenous] ketamine infusions."
One option might be to start patients getting a single ketamine dose on an approved monoaminergic antidepressant or mood stabilizer, Dr. Zarate and his colleagues suggested. "Even though patients may have previously not responded to this medication, it might still help maintain an acute response to ketamine."
However, they concluded, "this type of approach, although practical, remains speculative at this point, and future studies are clearly needed."
Dr. Zarate has a patent application for the use of ketamine in major depression. He has assigned his rights to the U.S. government, but will still receive a share of any royalties that might be produced. Dr. Duncan, Dr. Aghajanian, and Dr. Laje declared they had no financial conflicts of interest.