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Will ketamine help depression?

Asked by Jenn, Ohio

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Is ketamine IV promising for medicating resistant depression? What are the possible side effects?

Expert Bio Picture

Mental Health Expert Dr. Charles Raison Psychiatrist,
Emory University Medical School

Expert answer

Dear Jenn,

These are dark days for psychiatry. Recent studies have suggested that the medications upon which much of the field is built are not as effective as we once thought and have more side effects, some of them ominous.

And we've had almost no luck discovering agents that are either safer or more effective than what we've already got on tap.

We've discovered a lot about pathways in the brain and body that promote depression, but we've been so unsuccessful at bringing this basic knowledge to the clinic that many of the largest pharmaceutical companies have abandoned the pursuit of new psychotropic agents.

Against this backdrop ketamine is a ray of hope, or would be if it weren't for the fact that it is a dangerous drug of abuse that requires an intravenous injection for delivery.

Just our luck that the most promising antidepressant on the horizon comes with so much baggage.

Ketamine was developed more than 50 years ago as an anesthetic agent that would replace the even more dangerous drug phencyclidine, or PCP, which is commonly known on the street as "angel dust."

Like PCP, ketamine modulates the activity of the brain's main neurotransmitter, glutamate, by blocking NMDA receptors. At low doses ketamine blocks pain perception and produces a state of dissociation in which one feels that the self and/or the world is unreal. As the dose is increased this dissociative state becomes more intense and hallucinations -- often of a highly cosmic nature -- begin to emerge.

Ketamine first came to attention as a potential antidepressant while being used to treat chronic physical pain. This is not surprising.

We now know that physical pain and emotional pain are processed by the same brain regions -- almost as if emotional pain is a cerebral metaphor for physical discomfort.

As an antidepressant ketamine is unique in several ways. First, it appears to have a remarkably rapid onset of action. Whereas standard antidepressants take weeks to months to begin working, ketamine begins to powerfully reduce depressive symptoms within an hour of its administration.

Second, ketamine works in people who have failed every other treatment known to man, including electroconvulsive shock therapy, or ECT. Finally, and unfortunately, the antidepressant effect of a single infusion is relatively short lived, lasting from several days to several weeks.

All this gloom and doom aside, ketamine is -- in my opinion -- the most promising new antidepressant on the near horizon. If ongoing studies confirm its striking efficacy even in people who have failed everything else, I suspect it won't be long before it is widely available.

In the meantime a number of academic centers around the country are providing it on a limited basis.

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