Michael Thase, MD: Can Ketamine Curb Depression?

Michael Thase, MD:

The interesting, more exotic treatments in development are descending from a serendipitous observation that the anesthetic ketamine, administered at sub anesthetic doses — either 0.4 or 0.5 milligrams per kilogram in an IV infusion – can have dramatic antidepressant effects in a time course unlike any other treatment we've ever had.

To me, the fascinating thing about this is that the intoxicating effects of sub anesthetic doses of ketamine — the things that drug abusers use it for – happened within an hour or 2 hours, no more than 2 hours. The antidepressant effects emerge within 24 hours, whereas the intoxicating effects are gone within an hour. The antidepressant effects that last for 4, 5, 6, 7 days.

The other fascinating thing is that if you have a trippy experience with the infusion of ketamine, you have a dissociative experience or a psychotic emetic experience, it says nothing about whether it's going to help you as an antidepressant. So there are people who get the antidepressant effect who have had zero kind of psychedelic activity, and there are people who have a lot of psychedelic activity with the infusion who don't get the antidepressant effect.

So this suggests that the target for drug abuse and a psychotic mimetic experience is different than the target for the antidepressant effect, which leaves open the possibility of newer generation treatments working through the same pathway that may not have the baggage that ketamine itself has.