Hope in Treatment-Refractory Depression

Bret Stetka, MD; David Feifel, MD, PhD


January 10, 2013

Editorial Collaboration

Medscape &

In This Article

The $64,000 Question

Medscape: How long do the beneficial effects of ketamine tend to last?

Dr. Feifel: That is the most important question right now. Typically, we are seeing 4-10 days of benefit. A small group of patients did not respond at all, and in others, the antidepressant effects were gone within a day. The effects usually last a week, plus or minus 3 days.

Medscape: That's a significant duration. For someone in such a bad state, I would think a week can be pretty meaningful.

Dr. Feifel: Exactly. Many patients are so desperate to experience some relief of their depression that the tell me beforehand that if the effects of ketamine last only a couple of hours, or even just the 40 minutes' duration of the infusion, it would be worth the effort and cost. Having their depression turned off, even for a brief time, is a big deal to someone whose entire waking existence is unrelenting misery, hour after hour. It's not just that they feel better for an hour or two. For many patients, the remarkable recognition that their depression can be turned off, that they can feel good and remember what it is like to feel good, renews their hope for pursuing treatment.

The big challenge now is how to translate that short-term benefit into a lasting benefit to the patient. Our initial instinct was to administer an intense series of 2-3 ketamine infusions weekly, over several weeks, similar to the way electroconvulsive therapy is administered, with the idea that if you give an intense series, you may be able to convert a transitory effect into something more durable. However, l was dissuaded from taking this approach by emerging research findings that were not encouraging. One study[3] showed a median 18-day sustainment of benefit after an intense infusion series. That might be a little bit longer than the duration of benefit following a single infusion, but it's not long enough to justify giving 6-9 infusions over a short period of time. Therefore, I don't believe this intense infusion series approach is going to be the answer to converting acute responses into more chronic improvements.

Right now, in the UCSD program, we are more oriented to a repeat treatment for maintenance approach. We look at a patient's first infusion to answer some important questions. Does ketamine work in this patient? If so, how long do the benefits last? If they last only a day, it is very challenging, and we focus our efforts on figuring out how to convert it into a longer effect. But for patients in whom the benefits of the ketamine infusion last at least a week, some sort of repeat treatment maintenance schedule can usually be developed. We now have a small group of patients who are on such a maintenance regimen. Although it is very early, so far, some of our patients have been on such a maintenance regimen for months, and it has profoundly changed their quality of life.

There is a cyclical aspect to ketamine infusions; patients feel better for a week or more, and then they go through the usual gradual dissipation of the effects. However, a second-level progression occurs over weeks to months, in which the baseline symptoms of depression seem to be improved. When the patients come in for their next treatments, they are not as depressed as they were before ever receiving ketamine. We don't know whether this improvement is a reflection of long-term pharmacologic effects of the drug slowly healing their depression or the result of psychosocial aspects -- they have more depression-free days and that experience in itself may be inducing a gradual improvement. They no longer expect to feel only misery; they expect to feel normal even when they are in the part of the treatment cycle where the overt benefits of ketamine have worn off. Over time, we are seeing that feeling better might be therapeutic in itself, and perhaps patients will need fewer ketamine treatments.