Commentary

Is ketamine living up to the promise for depression?


 

Dr. Sederer: There is another feature of ketamine, in that it also has a pronounced benefit for suicidal ideation, which your research has reported on.

Dr. Mann: Yes, we’ve learned over the years that depression and suicidality are in some ways comorbid conditions. That both have to be addressed in order to keep somebody alive so that they can respond to treatment.

That’s a very important point. If the patient is suffering from depression and the antidepressant takes weeks to work, they may lose hope during that time. They may become overwhelmed by the suicidal ideation, no longer able to control or resist the impulse to take their life. A lot of the management is therefore to try to help support the patient (and family) so that these thoughts never become too compelling. Often we have to consider hospitalization to protect these patients so that they can stay alive long enough for the antidepressant to work. But ketamine not only has this very rapid effect for their depression, it also has a partly independent effect on suicidal ideation that is equally rapid and robust, which can render the patient safer.

Dr. Sederer: In other words, it’s effective and rapidly so for depression, with a bonus of reducing suicidality? This sounds almost too good to be true.

Dr. Mann: There are some limitations that we have to keep in mind. One limitation is that a single administration of ketamine will produce this robust improvement but it will only persist for most people for 5-7 days.

Dr. Sederer: Is the same duration true for scheduling the next treatment as well?

Dr. Mann: Yes, it is. The patient will gradually begin to deteriorate if you do not repeat the treatment. But as we showed in our randomized controlled clinical study, with ketamine for suicidal ideation, if you continue to deliver the medication, you can sustain the benefit.

Dr. Sederer: Can a person receive both ketamine and a conventional antidepressant at the same time?

Dr. Mann: Yes. In this study, half of the patients were actually continued on their previous medication while we added the ketamine on top of that. It worked very well.

In practice, people use two approaches. One approach used by most ketamine clinics is to give six doses of ketamine at a frequency of about two per week. Then they will reduce the frequency down to once a week for a few more doses and then once a month.

Dr. Sederer:: And this is a ketamine infusion?

Dr. Mann: Yes, this generally has been a ketamine infusion. This approach seems to work quite well. But that may not be necessary.

Another strategy is to give one, two, or three doses of ketamine. If the patient doesn’t respond robustly to two or three doses, they’re not going to respond to subsequent doses.

Dr. Sederer: So, initial responses are a predictor of future response?

Dr. Mann: Exactly. Now, if they haven’t done well with two or three doses, then you’ve got to use other treatments. But if they do well with the two or three, then you’ve got a choice: You can either complete the treatment course with ketamine and then continue them on antidepressant medications, or simply treat them with ketamine alone. What we tend to do is to treat with only antidepressant medications after a small number of ketamine treatments. We also use ketamine as a kind of “rescue medication” if they relapse into severe depression, though this is true for only a minority of patients.

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