Ketamine is the source of some controversy: it works wonders for depression, and fast. But it’s also addictive and potentially triggering for people in recovery. It’s proven to effectively treat severe depression that won’t respond to other medications. But because it affects so many receptor sites in the brain, and because it causes hallucinations and other psychedelic effects, there’s a lot to consider. Former Chief Medical Officer Marvin Seppala, MD, joins host William C. Moyers to discuss.
0:00:13 William Moyers
Hello and welcome to Let's Talk, a podcast series produced by Hazelden Betty Ford. Today our topic is, well, it's controversial: Ketamine. Is it an effective drug to treat people with depression? I'm your host, William C. Moyers, and my guest today is none other than my colleague who also is a dear friend and fellow traveler, Dr. Marvin Seppala. Welcome, Dr. Seppala.
0:00:39 Dr. Marv Seppala
Thanks a lot, William! Glad to be here!
0:00:41 William Moyers
You know, you really don't need any other introduction. We've done podcasts in the past. But I think I should for the benefit of my audience. Tell them that you are a renowned Psychiatrist who turned your personal experiences into your role as a national and international leader on all things addiction. Especially treatment and integrated evidence-based practices. And the healing power of recovery. There's so much we could talk about but if you would just briefly share with us how it was that you came to addiction medicine.
0:01:14 Dr. Marv Seppala
Well, you know, it was my own recovery. And I was in medical school, two years in, thinking I'd be a cardiac surgeon. And I saw all these people with addiction during my initial clinical rotations in the hospitals. And it wasn't being identified. We were not doing anything about it. we weren't suggesting a consult or suggesting treatment. We did nothing. And I was going to a Twelve Step meeting at the time complaining about this week after week. And two doctors in the meeting took me aside one day and said, 'Marv, you have got to quit bitching about this and do something about it!' [laughs heartily] And that—and it opened my eyes to possibilities besides surgery. And I became a Psychiatrist and did an addiction fellowship.
0:02:04 William Moyers
[nods, smiles] Well we're glad you opened your eyes and did that. And we're so glad that you've been part of the Hazelden Betty Ford mission for so long now. Let's talk about Ketamine. What is it?
0:02:14 Dr. Marv Seppala
You know Ketamine is a dissociative anesthetic. So what that means is that it actually relieves pain, so it's not just for anesthesia, it also relieves pain. So it puts people to sleep, relieves their pain. But, they are awake so to speak. Their eyes aren't closed. Unless people close them or take them down. They don't feel anything. And, in addition to that, it's considered like I said for pain and analgesic, you could take some, you could take some Ketamine liquid. You can get Ketamine lotion for like joint pain and rub it on yourself. It's prescribed. And it's also an antidepressant. Which is one of the reasons that we wanna talk about it today because it's being used for treatment-resistant depression. So the worst of depression. That hasn't responded to anything else. It's also described as a psychomimetic so basically a psychedelic, you know. It can cause hallucinations and dissociative experiences like out-of-body type experiences, that sort of thing.
0:03:30 William Moyers
So why the debate?
0:03:32 Dr. Marv Seppala
Well the main debate is should people that are in recovery or have substance use disorder actually use this medication for the treatment of depression. So it's especially concerning to people currently providing it for depression. Because they don't wanna trigger a substance use disorder or, you know, cause a relapse for someone that's in recovery that also has depression. And there isn't enough information yet to know whether that would happen or not.
0:04:02 William Moyers
Is Ketamine addictive?
0:04:05 Dr. Marv Seppala
It is, you know, it's unlikely to be I would say in a general way. Most people don't use it frequently enough to become addicted to it. But there are people that have and there's descriptions of it and even in the DSM-5, the Diagnostic and Statistical Manual of, you know, mental health disorders. It is listed under Phencyclidine-like substances as addictive.
0:04:32 William Moyers
Do we see many patients at Hazelden Betty Ford or generally in the field of addiction medicine? Are there patients who are actually seeking treatment for it?
0:04:42 Dr. Marv Seppala
We don't see a lot, that's for sure. We see occasionally somebody. In general what we see is younger people using multiple different substances and becoming addicted to let's say, you know, marijuana or cocaine or even opioids that occasionally just take Ketamine because their friends are doing it or they're going to you know a dance party or something, where it's commonly used.
0:05:07 William Moyers
As we focus on its use and application with depression, how does Ketamine affect the brain exactly?
0:05:17 Dr. Marv Seppala
You know, it primarily affects the brain through the NMDA receptor system. An unusual system that has to do with a lot of brain activity. It's also associated with addiction to a degree. And it basically—we don't fully understand it because it affects multiple different receptor sites across the brain. Including almost all of the receptor sites that antidepressants affect. Like norepinephrine, dopamine, sites like serotonin. But it also affects new opioid receptor sites where the opioids themselves bind to relieve pain and to cause intoxication. So it's a really complex medication actually. I believe there's at least twenty different receptor sites in the brain that it's affecting. And so we don't understand the whole of its medication very well at all and exactly how it works.
0:06:23 William Moyers
So are there any outcome studies or is there any data that proves or disproves its effectiveness for the treatment of depression?
0:06:32 Dr. Marv Seppala
There is. There's a great deal of information about it in regard to depression. So, it was first looked at for depression in 2000. And studies started to occur shortly after. Now there's been meta-analysis, so an examination of multiple studies to give data as well. And it does reveal that it works extremely well for depression. And extremely fast, which really is two of the things that the antidepressants don't do. About a third of the people that take a traditional antidepressant don't respond to it. And, they take four to eight weeks to start kicking in, and that's just to start kicking. So even longer to really start to relieve depression. Well Ketamine quite differently works almost immediately. So within 24 hours you start to get relief, of the depressive symptoms. Which is just remarkable and especially dramatic. Like in psychiatry, we just don't see things happen that fast. I talked with a woman Psychiatrist at Mayo Clinic who's run a clinic for Ketamine for the past three years. And she said that her patients and the family members thank her and just right away. Like, 'I feel so much better. I feel relieved of this horrible burden, this depression.' And depression is a horrible burden. I mean, it's the most common debilitating illness worldwide. 300 million people. You know? And it undermines a person's ability to interact with other people, it undermines their work, undermines almost every aspect of a person's life. So, to get sudden relief is, you know, we thought it was a dream basically. It was always the goal of treatments for depression. So there is reason for optimism about this medication. Tremendous optimism.
0:08:42 Dr. Marv Seppala
And it's only thus far being used for treatment-resistant depression. Basically. Or for people that are very depressed and suicidal and not responding to the first medication. So, treatment-resistant depression means they've had at least two traditional antidepressants and they haven't worked. That's the general rule there. You know, people with these Ketamine clinics are giving it to a lot more people than those, but, you know, the folks that are doing this right are just providing it for treatment-resistant depression 'cause that's how the FDA approved it. And so the people that have the most difficulty, the worst depression. The Psychiatrist at Mayo I talked with described they are often working with people that have had five, six, seven antidepressants. Or had ECT, Electroconvulsive Therapy, and they don't get relief. I mean these are really seriously affected, severe illness depression. And approximately 60 percent or so get relief from Ketamine. So the data is actually really good in the studies. Dealing with some of the people that have the most severe types of depression.
0:09:58 William Moyers
We talk about depression and we know that depression is a mental illness. We also know at Hazelden Betty Ford that a large percentage of our patients come to us with what we call a co-occurring disorder. They have both a substance use disorder and they have a mental health condition. Can Ketamine be used in an addiction treatment regimen?
0:10:22 Dr. Marv Seppala
So far, that question has not been answered. Because most of the studies on Ketamine excluded people with substance use disorders. 'Cause they were concerned about the potential for triggering addiction or misuse of Ketamine. Now, you can't—they don't prescribe Ketamine, you have to go in and they either inject it IV or they give you a nasal formulation. And you've gotta stay there a few hours to be sure that you're okay. Because it is an anesthetic, it does all those things I described earlier. And if you're really sensitive to it, it can be problematic. You could start having hallucinations, disassociation, you could actually get to the point that you can't move because, you know, it's had this anesthetic effect. That's unusual 'cause they're smaller doses than anesthetic doses. But it can happen. So you can't really have access to it. but you can certainly buy it on the internet and on the street, right? [chuckles] So, it's available. And as a result, they've been very cautious. And because it is potentially addictive and we've seen that among our patients and it has been described elsewhere, people are just really cautious about giving it to our patients. So, however, if someone who has a substance use disorder and is in recovery, and good solid recovery, has a severe depression that hasn't responded to a couple of antidepressants and is just getting suicidal and despondent, this could be a really good choice. And you could structure it in a way with the providers and the family to really monitor for, you know, potentially stirring up their substance use disorder.
0:12:14 William Moyers
Do we currently—we being Hazelden Betty Ford—do we currently utilize Ketamine?
0:12:20 Dr. Marv Seppala
We do not. We don't. And one thing I didn't mention earlier—and we don't because it's still, you know, really new. It's only been three years since it was approved by the FDA. And since it hasn't been studied for those with substance use disorders, if we were gonna go into its use we'd start with a study. Perhaps, you know, partnering with some other group to see just how safe it might be. But currently we haven't. But one of the things I didn't mention is you don't just get one dose of Ketamine. It works really fast, but it also—the effect resolves really quickly. Like within a week. So it'll last about a week when you first start taking it. And then you gotta have another dose. And then, a week later another. And that's usually the first month. Then they might be able to go—and in fact they'll do two, three doses a week at first. To be sure that you're getting an adequate amount of the medication and adequate concentration, it's gonna have its effect. And then over time, over the next you know month or so, they'll decrease that frequency. But it doesn't tend to be a lasting response. And the FDA requires that you continue an antidepressant while you take it in hopes that that antidepressant will take over for the long term and prevent a return to depression. But, right now that's not even clear. If it has to be continued over time or not. So it's a long-standing commitment if you start using this. It's not covered by a lot of insurance companies and it's really hard to get them to cover it still. In spite of the dramatic effects that it has for the most difficult disease, you know? The people that have the most severe depression.
0:14:12 William Moyers
Mmm. We only have about a minute left, Dr. Seppala, and what I'm gonna ask you really begs for a deeper dive. And perhaps we'll do a podcast on this subject as well. But I know that there'll be some people who are watching who are interested in the applicability of drugs like Ketamine and other drugs in exploring consciousness or treating mental illness, or treating addiction. So, let me just ask you briefly about psilocybin. And microdosing of psilocybin. What is your response not only as an addiction psychiatrist, but a person in long-term recovery, to the use of hallucinogens in the treatment of addiction or in the exploration of consciousness?
0:14:56 Dr. Marv Seppala
So, the difficulty lies in the same manner that we just discussed about Ketamine. Would the use of even microdosing trigger addiction? Because, you know, I'll use Ketamine as the primary example. When they've given Ketamine to animals it's reinforcing they want more. When they've done surveys about people who don't have a substance use disorder and ask them did you like the feeling, most people say yes. And if they ask people who have a substance use disorder, they always say yes. [Both laugh] You know? And so, the potential exists that even microdosing of psilocybin could trigger relapse or continued use or a change in addiction. Now, I certainly know people who have used hallucinogens in the course of recovery in like traditional sort of religious ceremonies and found that to be a structure that worked really well and allowed them to explore consciousness in a different way. And perhaps that's possible. But, I think we have to be extremely careful as people in recovery about such use of any kind of a potentially addicting medication.
0:16:12 William Moyers
Well, we'll have to follow up and have another podcast to dive into that. Because that is a controversial and an interesting topic. I know a couple of books on the New York Times bestseller list now by Michael Pollan are all about microdosing and the use of psilocybin, and the use of marijuana to treat opioid use disorder, and all those other things that we'll talk about another time. But Dr. Seppala, it has been a pleasure to have you on. We always, always appreciate you joining us to share your expertise, your wisdom, and your passion with us. So, thank you very much, Dr. Seppala.
0:16:43 Dr. Marv Seppala
Thanks a lot, William!
0:16:45 William Moyers
See ya again. [turns to camera] And thanks to all of you for joining us. Remember, addiction to alcohol and other drugs does not discriminate. But treatment can work and recovery is possible. So don't wait if you or a loved one needs help. Ask for help, do it now. I'm your host, William C. Moyers, I hope you will join us for another edition of Let's Talk. See ya soon.