Dr. Sederer: What are the differences you’re discovering between esketamine and ketamine?
Dr. Mann: It is a bit different. We’ve just completed a very important National Institutes of Health–funded clinical trial here at Columbia showing that with esketamine or ketamine itself, the dose and the blood levels are very closely related to the robustness of the clinical response.
When you give a drug intravenously, you give a very reliable dose. When you give the drug over 40 minutes, you’re spreading the dose administration over a period of time so that it doesn’t peak very high. The side effects appear to be proportional to the peak dose.
When you give it intranasally, you give the drug over a much shorter period of time. Even if you use more than one intranasal administration to give the whole dose, it’s still a relatively shorter time, compared with the 40 minutes.
Dr. Sederer: This means that to get the equivalent dose intranasally, the patient is going to have to experience a higher peak. Can you predict that those patients who are treated intranasally are going to have more side effects?
Dr. Mann: Right. And that should be explained to the patient. You will not need an intravenous line inserted, which some people might find highly appealing and advantageous, but you will probably have more side effects.
Also, in general, intranasal absorption of drugs is more variable. The predictability of the blood level and, therefore, the degree of antidepressant effect is not as good intranasally as intravenously.
Now, all of this is anecdotal clinical experience, based on theoretical pharmacology, because nobody has actually done a head-to-head control comparison.
Dr. Sederer: What about the cost of both of these preparations?
Dr. Mann: There is a bit of a range in pricing between ketamine clinics around the country. It’s always important to find out what they charge per administration. And then it makes a difference whether you have two or three administrations versus six plus further tapered administration. Clearly, the cost can vary a great deal.
Dr. Sederer: But it’s generally not covered by insurance, so most people are paying out of pocket.
Dr. Mann: Yes. The intranasal ketamine is still in negotiation at the moment, but it should be resolved before it’s fully marketed.
Dr. Sederer: Ketamine is used for major depression. Does it have utility in bipolar depression?
Dr. Mann: We and some others have done initial studies in bipolar depression. In our view, it’s probably going to be as effective in bipolar disorder as it is in major depressive disorder, unipolar depression.
We haven’t seen any manic episodes triggered, but we don’t give repeated doses. We allow research patients to stay on anticonvulsants or mood stabilizers, so that’s helpful. Generally, people with bipolar disorder who come for ketamine treatment for their depression are coming on a mood stabilizer, because that and perhaps other conventional antidepressants have not proven to be effective. So, I think that ketamine plus mood stabilizers seems to be very promising.
Dr. Sederer: I want to return to the antisuicidal properties that you had previously mentioned. I heard from a colleague about a patient who had been admitted to a psychiatric inpatient unit. The patient was in her 20s; she did not have major depression but was persistently suicidal, constantly trying to hurt herself in any way she could. But that seemed to be more a product of borderline personality disorder, with its impulsive and self-destructive problems.