COMMENTARY

Is Ketamine a Viable Antidepressant?

Scott A. Irwin, MD, PhD

June 12, 2012

Editorial Collaboration

Medscape &

Editor's Note:
Below, Dr. Scott Irwin of the Department of Psychiatry at The Institute for Palliative Medicine at San Diego Hospice, responds to a recent Medscape Psychiatry commentary addressing ketamine's potential role -- or lack thereof -- as an antidepressant.

I would like to comment on Dr. Michael Thase's assertions regarding ketamine in the Medscape Psychiatry piece "Three Depression Therapies to Watch." While touting the rapid antidepressant properties of ketamine, highlighting its differing mechanism of action from currently available antidepressants, he also states that "The fact that it has abuse potential and has psychomimetic and dissociative effects really prevents it from being considered as a potentially useful antidepressant." He goes on to say that if the antidepressant effects can be "uncoupled from, or not invariably associated with, the psychomimetic or the dissociative properties...that different aspects of the N-methyl-D-aspartate (NMDA) receptor can be targeted -- hopefully, with retaining the antidepressant effects without the abuse potential, or dissociative or psychomimetic properties...."

I would like to take issue with the comments by Dr. Thase regarding ketamine not being a viable antidepressant owing to its abuse potential, psychomimetic, and dissociative effects. Physicians, especially psychiatrists, use many drugs with abuse potential (eg, benzodiazepines, bupropion) and unwanted side effects (every medication known to man) all of the time. Physicians sometime use medications with abuse potential (eg, opioids) safely and effectively in patients who need them (eg, cancer pain) but also have abuse histories.

When properly monitored and managed, issues of abuse and adverse effects can be detected and dealt with effectively. The psychomimetic and dissociative effects with intravenous ketamine are not pervasive, nor are they long-lived.

Recent work by Dr. James Murrough and colleagues at Mount Sinai's Mood and Anxiety Disorders Program supports the viability of low-dose intravenous ketamine in treatment-resistant depression.[1] And at San Diego Hospice and The Institute for Palliative Medicine, we have had experience using oral ketamine, dosed daily, in over 30 patients. While data are currently being analyzed, preliminarily it looks like we're seeing at least a 65% response rate, with some patients responding in hours and others responding more slowly over a few weeks.

We also see more dramatic decreases in symptoms of anxiety than we do with depression. The positive effects last for weeks to months, and if they wane, we can get them back by increasing the dose. With the oral route, we do not see the dissociative or psychomimetic effects. In fact, in our patients who already have a high baseline somatic symptom burden, most somatic symptoms improve.

However, these comments should be considered carefully, as they are based on open-label trial data and retrospective clinical chart reviews. Clearly, randomized trial data are needed. Furthermore, no studies to date have looked at the effects, positive or negative, of the long-term administration of ketamine. Although we have used it for months in patients with no emerging issues, we also work with a population that will not be taking it for years.

Even though much more research needs to be done on the viability of ketamine as an antidepressant, why discard a potentially viable existing medication that is cheap, widely available, and easy to use by multiple routes? In an era in which increased healthcare quality with decreased healthcare costs are a focus, and in the spirit of healthcare reform -- including a push to repurpose existing drugs and engage in comparative effectiveness research -- should we be pushed down the path of new drug development, potentially costing the public billions in either insurance premiums or tax dollars? Perhaps, if we truly get something worth the investment. Or should we invest in further investigation of something we have that shows promise, as healthcare reform suggests?

Perhaps the answer is both. Clearly, thoughtful consideration by researchers, clinicians, policy makers, and the public is required.

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