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Shrink rap news: is Ketamine on our radar yet?

It's been a few years since I first heard about the use of intravenous ketamine leading to instant relief of depression symptoms, relief that lasts longer than the ketamine does. It sounds like a miracle cure.

The current issue of CLINICAL PSYCHI-ATRY NEWS features a front-page article about the value of oral ketamine in treating patients not only with depression but with anxiety disorders ("Psychostimulants, Ketamine Lift Depression Quickly in Hospice"). In recent months, I've been hearing about it a lot, especially on National Public Radio (NPR).

While turning to Google and PubMed to examine the latest evidence, I am simultaneously wondering why I've not heard of anyone I know using it to treat depression. After all, ketamine is a Food and Drug Administration approved drug, and thus can be used offlabel. It is available as an oral drug, which I know mostly because "Special K" has been used as a rave drug for years.

And people are out there with treatment-resistant depression who could benefit from it if the risks are not too high. Note: The dose used for depression is only 1/10th (0.5 mg/kg) of the common hallucinogenic dose used on the street (350 mg according to Erowid).

As it turns out, ketamine was featured on many NPR shows a couple of months ago. Jon Hamilton's story on Morning Edition featured a man who has had numerous medications to treat his major depression, which he rattled off: "Klonopin, Ativan, Valium, Xanax, Re-meron, Gabapentin, Buspar, and De-pakote." I heard this story in the car and thought to myself that only one of those eight drugs is considered to be an anti-depressant. That's one of the problems we face: inadequate depression treatment. Either the wrong drug (Xanax) or the wrong dose (50 mg of Zoloft).

Neal Conan on NPR's Talk of the Nation devoted an entire show to ketamine. The transcript is worth reading (and the audio worth listening to). This blast of publicity about ketamine is likely fueled by the randomized, controlled add-on trial published by Dr. Carlos A. Zarate Jr. and his colleagues using ketamine with 15 people who had severe bipolar I or II depression (Biol. Psychiatry 2012 [doi:10.1016/j.biopsych.2011.12.010]). Seventy-nine percent of the patients who received one intravenous infusion of ketamine had a "rapid and robust antidepressant response," and placebo had no effect.

While ketamine's effects could be related to its glutamate receptor antagonism, another potential mechanism has been invoked.

The mammalian target of rapamycin (mTOR) is activated by ketamine, and preventing its activation also prevents the antidepressant effects (at least, in animals).

Anyway, Dr. Zarate, of the National Institute of Mental Health, was featured in some of the NPR stories, and he thinks that ketamine's tendency to induce hallucinations will prevent it from being widely used for depression. But, until we have another FDA-approved NMDA antagonist to use, there are surely many people "living with the black dog" who would gladly risk a bad trip to cut the dog's leash. Meanwhile, a Yale University study used openlabel ketamine for acute depression with suicidal ideation in the emergency department (Int. J. Neu-ropsychopharmacol. 2011;14:1127-31).

All of this makes me wonder how many psychiatrists reading this article have tried prescribing ketamine for their patients. Let us know.

DR. DAVISS is chair of the department of psychiatry at the University of Maryland's Baltimore Washington Medical Center, and co-author of Shrink Rap: Three Psychiatrists Explain Their Work, published by Johns Hopkins University Press. E-mail him at
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Title Annotation:OPINION
Author:Daviss, Steven Roy
Publication:Clinical Psychiatry News
Date:Apr 1, 2012
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