For years, physicians have been inching their way to a better understanding of how -- and how well -- the drug ketamine, a “twilight drug” used to sedate some patients before a painful procedure, can lift someone with severe depression almost immediately from the abyss.

A new study, presented in San Francisco this week at the American Psychiatric Association’s yearly meeting, shows that ketamine’s rapid antidepressant effect is no incidental effect of sedation: it’s real, and it lasts -- albeit with diminishing effects -- for at least a week.

Ketamine, which is also a drug used recreationally to achieve a sort of “out of body” high, “is not at all ready for prime time,” said Dr. James Murrough, an associate professor of psychiatry at Icahn School of Medicine at Mt. Sinai. But it is approved for use in anesthesia, so it’s available legally. And years of small and preliminary trials have offered tantalizing evidence of its powerful and fast-acting antidepressant effect on patients whose depression has failed to yield to other treatments.

The result, said Murrough, is that some physicians appear to be using it already in patients.


“That reflects desperation out there” for antidepressant medicine that does not take between four and six weeks to take effect, as is the case for many patients with the most widely used class of antidepressants, the Selective Serotonin Reuptake Inhibitors (SSRIs). But the fact that ketamine is already being used off-label makes good clinical research on its safety and effectiveness a matter of urgency, said Murrough.

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At Icahn School of Medicine’s Mood and Anxiety Disorders Program, researchers recruited 72 people whose major depressive disorder persisted despite trials of two or more antidepressants. Half of their subjects were given a single, 40-minute infusion of ketamine at a much lower dose than is used in anesthesia. The other half got a 40-minute infusion of another sedative, midazolam, which is not known to have an antidepressant effect.

A day later, both groups’ depression had abated, but the response rate among those who got the ketamine was stronger -- 63.8% vs. 28% in the midazolam group. A week after the infusions, the ketamine group’s response rate had fallen to 45.7%, but remained much stronger than that among the midazolam group, which had a response rate of 28% at the end of a week.


Murrough said the subjects who got ketamine seemed to suffer no ill effects from their infusion. “It seems eminently safe and tolerable,” he said. But if the medication needs to be re-administered periodically or on a regular schedule, the safety, effectiveness and dosing schedules of its longer-term use -- an ongoing subject of clinical trials at the Mt. Sinai programs -- will have to be established, he said.