Hope in Treatment-Refractory Depression

Bret Stetka, MD; David Feifel, MD, PhD


January 10, 2013

Editorial Collaboration

Medscape &

In This Article

Editor's Note: Severe, treatment-refractory depression is one of the most challenging conditions facing psychiatrists. And, unfortunately, it's very common. Now, an old drug -- ketamine -- is having a renaissance in psychiatry and is offering hope to patients unresponsive to standard antidepressant therapies. Medscape recently spoke with David Feifel, MD, PhD, Professor in the Department of Psychiatry at the University of California, San Diego, about his experience with using ketamine in the treatment of depression.

Ketamine: Old Drug, New Tricks

Medscape: We've been hearing a lot about ketamine's potential as a psychiatric medication lately. Can you give us some background on the medical and cultural history of the drug?

Dr. Feifel: Ketaminehasbeen approved for veterinary and human use as an anesthetic agent for decades. It produces a type of anesthesia called a "dissociative anesthesia," meaning that it tends to dissociate or cut off the physical sensation of the body from the mind. Ketamine is used every day in medical centers around the world, including my institution, UCSD Medical Center, as an anesthetic and as an analgesic for intractable pain. However, the latter use is somewhat controversial, in terms of the potential long-term benefits.

Ketamine is also used illicitly for recreational purposes, typically as part of the club scene, and in this capacity it goes by various names, such as "Special K." Pharmacologically, ketamine is related to other known street drugs such as phencyclidine (PCP), also known as "angel dust."

Medscape: How is ketamine being used in psychiatry? And is this a relatively recent approach?

Dr. Feifel: Psychiatric use of ketamine is very recent and stems from research findings in patients with treatment-resistant depression. In such patients, infusional ketamine at a dose that is significantly lower than the anesthetic dose can produce a strong antidepressant response.

Not only do these challenging depressed patients respond, but the response is very rapid. Ketamine differs from anything we have with which to treat depression. The efficacy rate is higher than traditional antidepressant medications, and the onset of the antidepressant effect is almost immediate compared with conventional antidepressants, which have a latent efficacy that can take several weeks to fully manifest. This novel therapeutic profile is what has garnered so much attention for ketamine.

Medscape: Was ketamine's potential as a psychiatric drug an incidental finding?

Dr. Feifel: The recognition of its psychiatric potential came from a few seminal published research papers[1,2] in which ketamine was tested as an antidepressant against placebo and shown to produce high rates of efficacy and very rapid effects. A couple of investigative groups conducted fairly rigorous research that, when published, generated a lot of attention and excitement and made the field aware of the potential of ketamine for depression.