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Ketamine made headlines for the wrong reasons, and people who could be helped by it are staying away. Jim Ellwood is an anesthesiologist who has given ketamine in the operating room and taken it himself for depression that nine medications failed to touch. This episode is based on his article “The truth about ketamine: an anesthesiologist explains drug safety,” published on KevinMD. He explains what the research shows about how it works in the brain, and what to ask before you walk into a clinic. You will hear why he compares the panic around ketamine to what happened with propofol and fentanyl, how to find out who is actually writing the prescription at a clinic that advertises to you, and what he tells patients about how long the relief lasts and what it costs. He is candid about the stigma of a physician saying out loud that he has depression. Press play to hear a physician who has used ketamine both ways describe what a safe setting actually looks like.

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome Jim Ellwood. He’s an anesthesiologist, and today’s KevinMD article is “The truth about ketamine: An anesthesiologist explains drug safety.” Jim, welcome to the show.

Jim Ellwood: Thank you. Good to be here.

Kevin Pho: All right, so let’s start by briefly sharing your story and then describing why you decided to share this particular article on KevinMD.

Jim Ellwood: Well, I’m an anesthesiologist, so I had experience with ketamine as an anesthetic, and I’ve been dealing with drug-resistant depression for most of my adult life. I’ve tried nine different medications. I’ve worked with different therapists and psychiatrists. I’ve had periods where I do well, and I’ve had some short-term success. I’ve also had problems with drugs, side effects I could not tolerate.

So I was at a point about two years ago where I sought help again, because I felt I was going through one of my downs, and I was working with a therapist. We were making some progress, but she said, “It might be time to talk to a psychiatrist about adding on some medication.”

So I found a good doctor. He understood my situation. We tried at first a drug I had tried before, and it just did not do anything, and then we tried some newer approaches. I was not getting anywhere, and at one point I said to him, “You know, I’m curious about ketamine.”

When I had first heard about ketamine, I was very skeptical, because I thought, “Well, I know this drug as an anesthetic.” I had no idea. When people threw around things like, “Oh, it creates neuroplasticity,” I thought, “Well, that’s not necessarily telling me very much.” And the first time I inquired, it was a program that would send the medication to your home, and I thought, “No, I don’t think I want to do that.” It just seemed too risky.

But then along the way, obviously Spravato got approved, and it was now available for monotherapy. So I said to him, “Doc, what do you think?” And he said, “Look, I can’t prescribe it, obviously.” It was telemedicine. He is in another state. But he said, “You should look into it.”

And then I heard about Ketamedical, and it was run by ER doctors in a monitored setting with a strict protocol. And I said, “Well, let me inquire.” And they reviewed my history. They felt I met the criteria for drug-resistant depression. I did not have any medical problems that would have been an issue, so they said, “We can go ahead if you want to try it.”

The first time I tried it, I really did not know what to expect. The first experience was very strange, and I thought, “I don’t know how this is going to help me with my depression.” But they said, “Look, it’s a process. We’ll take a few doses.” And there was a ketamine-assisted psychotherapist who works with you to help you put the experience in perspective and help you understand it.

And within a short period of time, I went through a two-week induction period. I could feel a difference in my mood and in my perspective, and I felt very encouraged. So I stayed with it, and I started to feel like I was really making progress in therapy and with the medication.

And at one point I read an article, because a lot of the patients write little blogs and things about their experience. It was a professional; I think he was a lawyer. And he said, “I’m a person everybody looks at and asks, why are you depressed? You’ve got a family, you’ve got a career, you’re successful.” And he said, “I can’t explain it. It’s not a reactive depression to some specific event. It’s just this underlying mood disorder that I deal with all the time,” and how ketamine had helped him.

So I said, “Well, it’s an interesting story. I would like to tell my story.” And they said, “Please do.” So I wrote an article for them explaining how I was initially wary, because I knew something about ketamine and I could not understand how it could help. But I told them that it really had made a difference to me, and more importantly, the idea that as a doctor, I could come out and say, “Look, I have this problem, and I would like to acknowledge it.” I hope that my seeking help and having success would encourage other people to consider it. Particularly if you’ve tried medications and they haven’t worked, this could be something that would work for you.

So they published the article, and then along the way, as I spoke to friends and colleagues about ketamine, I got the typical responses. “Oh, it’s the horse drug.” And, “Oh, you’re in a K-hole like the kids at the clubs.” And I said, “No.” And even people who are anesthesiologists were like, “All right, fine as an anesthetic, but for depression?” I said, “Well, it works, and if you look into the research, they’re looking at the pathways and how it can help.”

Then of course what happened was the Matthew Perry story, and immediately there was a reaction: “Oh, this dangerous drug.” And there were all kinds of stories about deaths from ketamine, how it’s being abused, an epidemic of deaths from this drug, and people using it to get high and overdosing.

So I said, “Well, this is how psychedelics in general got into trouble in the early stages.” It was from the Harvard researchers to Timothy Leary turning on and tuning out. So I said, “Well, look, I’d like to make a comment about that.”

And in addition to that, then the story of Elon Musk came up, about him openly saying that he was using ketamine and using it to improve his mood, which I thought was a great thing. It could have been very helpful. Whether you like him or not is another story, but he was coming out. And then of course the stories started about him using excessive amounts of it and beginning to develop medical problems because of a ketamine addiction.

So I thought, I think what clicked in my head was my experience as an anesthesiologist with propofol and fentanyl. People came to me saying, “Oh, don’t give me that Michael Jackson drug. You’re not using that Michael Jackson drug?” And I’m like, “No, propofol is a great drug. It’s very safe. We use it all the time.” The problem was how it was used. It was used inappropriately.

Fentanyl, the same thing. Prince died of a fentanyl overdose. Tom Petty had fentanyl in his system. Various people were known to use it. And of course large quantities were being brought into the country, and people were overdosing on it because it was being mixed with other opioids. It was very powerful.

So I said, “I think the point I could make is that these are very good drugs when they’re used properly in the right setting, so don’t be afraid to consider it if you do it in a supervised setting with medical professionals, and it can really help you.”

And I use the analogy of something as simple as a knife. You don’t think of that as a deadly weapon. Well, it could be, but again, it depends on how you use it.

So that prompted me to write the article, and I thought it might help people to know that, one, this is an anesthesiologist. It’s not like he doesn’t know what ketamine is. He’s used it. He’s used it in multiple situations, and he’s seen it be safe and effective. And now he’s saying he’s using it for depression when he’s tried multiple drugs and multiple approaches, and this has been different from some of the things he’s done in the past. So I guess that’s really what prompted me to write it.

And then even when I visit my doctors, whether it’s my ophthalmologist or my internist or my cardiologist, I always tell them I’m on it, and why I’m on it, and I ask whether they know anything about it. And it’s still not that well known as a treatment for depression, although it’s getting a higher profile, because you can see now there are ads all the time for practices offering ketamine therapy.

And it’s also spoken of as a psychedelic, which of course has a mixed message. To some people, that’s alarming. It sounds like, what, are you getting high and tripping? And it’s even controversial whether it’s truly a psychedelic. I mean, it certainly causes dissociation, which I assume is what it feels like on a psychedelic. But it certainly creates that kind of experience.

I mean, to tell you, when I took it, there were just arrays of colors and geometric designs, and a feeling of expansion and connectedness. Which is kind of funny, because a lot of people who have psychedelic experiences talk about that almost sort of sheepishly, saying, “Yeah, everyone talks about this feeling of love or connectedness or expansion and so forth.” But it is something that you actually do. Many people do, and I certainly do experience it. So that’s part of what feels good.

And I do think, too, that the neuroplasticity part comes in, even in the research they’re doing. One of the first things I did was read Aldous Huxley’s book, “The Doors of Perception,” where he talked about a psychedelic experience. It’s like taking the brakes off. And sure enough, it does seem that one of the things ketamine does is sort of take the brakes off and allow you to jump out of your normal, restricted perception of yourself and reality, and see yourself in a broader context. So I think in some ways it’s that disinhibition that allows you to maybe say, “Hey, there are more ways to see things. Maybe there’s a different perspective you can have.”

Kevin Pho: The key word that you said is “when used appropriately,” and a lot of the time, when you hear about these celebrities using these off-label drugs, they’re obviously not using it appropriately. And when it comes to ketamine, as an anesthesiologist, you know it does come in different forms. You have the IV form, and you did mention Spravato, which is a nasal spray, which is the FDA-approved version. So tell us about some of the misconceptions that you want to clear up, and talk to us about some of the data, the research behind ketamine for treatment-resistant depression. How often is it used? And in general, how effective is it?

Jim Ellwood: Well, people throw out numbers like 55 to 60 percent or more of the people who use it are getting results from it. I don’t know how accurate that is, but that’s what’s being claimed. So it’s very effective.

And I know it was used, when I started looking back on it, it was being used IV and in some nasal forms by psychiatrists in controlled settings, to see if it would work. And of course, everything that was done was always in a supervised environment. No taking the spray home and trying it. The IV meant you stayed and were observed during it. So I think once it was shown that it could be done safely that way, there was a greater chance of getting it out to the public.

And people often say, “Well, it works by the glutamate pathway, where most of the psychedelics are more serotonin derived.” And that is true, but invariably, when you look at the ones that activate the glutamate pathways, other pathways are activated as well, including serotonin ones and opioid ones. And not surprisingly, it is not an opioid, but we use it for anesthesia, and obviously it does act upon opioid pathways. It can be addictive, for sure.

As a matter of fact, the American Psychiatric Association initially was very wary about use in people who had issues of addiction or substance abuse. And I’m sure now, even when you apply to one of these programs, they look back on your history to see if you have a history of substance abuse, because it could clearly be a risk.

But recently there was a group from Weill Cornell. They did some research and noticed that there are some interneurons, the part of the brain that regulates the prefrontal cortex, that seem to be overactive in people during stress, which quiets down the prefrontal cortex, where emotion and motivation and so forth, a lot of it derives from there. They found that it decreases that activity and, as they put it, frees up the prefrontal cortex.

And they also found that another thing that’s come up, brain-derived neurotrophic protein, there’s an increase in that, and this is the protein that acts in the nervous system to enhance connectiveness and improve communication between the cells. And they found that there are certain receptors that are activated that enhance connectedness between cells and may allow for some of the changes.

One of the issues that has been brought up with ketamine is that these effects are not long-lasting. And in one sense that’s one of the limitations of ketamine. I mean, I go weekly. Some people start to stretch it out to more than every week. They go every couple of weeks. It’s working for me and I’m not having any side effects. I’ve been doing it weekly, but there is a limitation on how long that effect lasts. So people are looking into ways of maybe enhancing it, or finding other ways of using substances that activate those pathways, as another example. And of course, there’s still research into the psychedelics, which people know have much longer durations of action. So that’s a little about that.

Kevin Pho: So as you said, these types of ketamine clinics are being advertised, and from a patient standpoint, how do they sort through all that information, whether they need to ask for something like Spravato or go to these IV ketamine clinics that they see advertised? How can patients sort through all that?

Jim Ellwood: Well, see, one of the things that concerns me, and this is from my own experience: I got a call one time, and a guy gets on the phone and says, “Dr. Ellwood, we have an opportunity you might be interested in. We’re running a laser cosmetic clinic, and we need a medical director.” And I said, “Well, I think you’ve got the wrong Dr. Ellwood. I’m an anesthesiologist.” “No, no, you’re a licensed physician. All we need is a medical director.” And I said, “Yeah, but I don’t really know about lasers.” “No, no. The people who run the setup, they know all about the lasers. The techs are all experienced. They know what they’re doing.” And I said, “Well, what would I be doing there?” “Oh, no, you don’t have to be there. You’re just the medical director.” And I said, “I don’t think this is a good idea.”

And then I had a friend, too, who owns his own home. He had a surgeon using an office there for years. When the surgeon retired, he got approached by a psychiatrist who wanted to run a Botox clinic, and he said to me, “Jim, is that legal?” And I said, “Yeah, it’s legal. If you’re a physician, you can be the medical director.”

So my concern would be, if you go to any outside service, you need to know who the doctor is, who is authorized. You can’t just give ketamine. You have to be licensed, and you have to have a DEA. So you have to know who’s doing it. And if you find out it’s the ophthalmologist who’s writing your prescription, maybe you wonder, is he the one who really knows how to assess it? But needless to say, I would want to know who is the medical person who is sending the prescription.

If you’re going to do it at home, you have to be comfortable with what would happen if there’s a problem. Who is with you? What would you do? What could you expect could happen? And then also, the medication is one thing, but after the experience, who is helping you with it? Who is your therapist? Is it someone who’s like a life coach, or a spiritual guide, or whatever? I mean, I think that’s important, too. You have to know what you’re comfortable with, whether you feel that that’s correct.

And in terms of the mode of delivery, oral medication, I have no experience with it. I don’t know what amounts to an appropriate dose. I can tell you there’s a website called Big Ten Ketamine, where a lot of the ketamine providers go and share information and so forth. The oral doses are striking in how much variation there is. So I guess that’s just individual differences, but again, how much are you taking? How much is absorbed? That’s something I don’t know how you would need to know, but you would need to have the discussion with someone: How do you determine how much I’m getting?

IV, obviously, that would be done at a center. There’s sub-Q, which again, I don’t know enough about. I’ve never given a sub-Q. I’ve given an IM, I’ve given an IV, I’ve taken the nasal version, but I’m certainly curious about how you determine how much. And also, if you’re giving sub-Q, do you know how to correctly inject, and needle safety? Are you making sure the vial isn’t contaminated? Are you sure you’re not putting too much in? Are you not tempted to put it in a vein because you’ve got a needle? I mean, I don’t think most people would think that way, but again, if you’re unsupervised and on your own, I think you have to be very wary. Think about those things before you would go that road.

Kevin Pho: From what I understand about ketamine and the risk of things like sedation and airway compromise, it’s especially in combination with things like benzodiazepines. And a lot of people with behavioral health issues are also taking those medications as well.

Jim Ellwood: Yeah, that’s a good point, because I know at Ketamedical the first thing they asked me was, “What medications are you on?” And I said, “The most recent thing I had been on was Lamictal,” which unfortunately did not help me. But they said they were particularly concerned about that. And I know this from anesthesia, that seizure meds can actually have a very big effect on how you respond to an anesthetic.

So not only would it be the SSRIs and the benzos, but people are taking other drugs, and someone would need to be knowledgeable about how that might interact with the ketamine. And it is true, I am not on any other medications, but many of the people who are using ketamine are on other medications, and that’s a good point.

As a matter of fact, even with the Michael Jackson death, I always point out to people that even though propofol was the problem, he had been giving himself IM injections, with an unpredictable absorption. Who knows what else he was taking? And so many of these things are multi-substance. When Tom Petty died, they found this, that, and the other thing in his system. So it’s true that, again, in an unsupervised setting, if you have other stuff on board, you should make sure that somebody knows what you’re doing and that you know what you’re doing, because again, the additive effects could make a big difference.

Kevin Pho: Now, as a primary care physician, and of course I see a lot of patients with treatment-resistant depression, what are some of the indications where I need to maybe suggest whether ketamine may be in that patient’s best interest? What are some typical scenarios?

Jim Ellwood: Well, I think a typical scenario is someone who has tried, particularly, the SSRIs, because so many of the drugs I tried were all just SSRIs, and for some people they simply don’t work. Because maybe that’s one thing in many people’s depression, but it’s not that in everyone.

So if someone tells you they’ve tried the SSRIs, saying, “Try another one, try another one,” I know that’s the typical approach. I think if you’ve tried a couple without any good effect, or you’ve had intolerable side effects, because let’s face it, if something gives you ED, if something causes other problems that complicate your life, that’s not going to help you. In the midst of your troubles, if you add on other things from the drug effects, that’s a problem.

But I would say, have they used other drugs? Are they in therapy? Because talk therapy can often be a big help, and then in conjunction, even now, with the ketamine, I don’t think it would be so useful for me if I weren’t working along with therapy. So are they in therapy? Have they considered it? Has that ever done anything for them? Have they made any attempts to address what the issues are? And then maybe a medication would be helpful.

I remember when I was working, we had a conference at the place I was at, and it was just, this doesn’t happen anymore. The drug company sponsored the conference, and they were encouraging all these primary care doctors to use their latest antidepressant, to help people. So I raised my hand and I said, “Wait a minute. I’m not knocking the primary care doctors, but should they be the ones who are the primary providers with a mental health problem?” “Well, no, but people can’t afford therapists. Not everybody has time for psychotherapy, so you can give them this medication.” I’m like, “Well, yeah, but is that really helping them?”

Out of context, putting somebody on an SSRI, I’m not saying you can solve their problems, but just medicating somebody so they don’t feel so bad is not necessarily the best thing. I think you could say, let’s do this as a way, and let’s look at maybe some other solutions. But I realize that’s easier said than done.

I mean, I can tell you from personal experience, finding a provider who accepts your insurance is a major, major issue, and it’s a major issue with ketamine. Many of these clinics, the first thing you have to address is whether you have insurance. And it can be pricey, so it becomes hard.

So I guess when anybody comes with a problem, you have to kind of get a sense of where they are financially, what is possible for them, what have they tried. And again, I think one of the big things is that you can go into something with an open mind and just say, “This may or may not work.” And the other problem is the time, the onset time. Telling somebody it could be 4-6 weeks before something works is a reality. And if anybody goes on that, so they don’t become discouraged, I think it’s important to emphasize, look, this may be a while before you feel a difference.

Kevin Pho: Do most insurers cover ketamine treatment, and if not, in general, how much does a course cost?

Jim Ellwood: Well, I have Medicare and Medigap insurance, which fortunately at Ketamedical they accept. I know I’ve had people go and they’re just told, as a matter of fact, at Ketamedical they don’t offer Spravato without insurance. So it must be pricey. I know it’s $500 for an IV ketamine session. And I don’t know what it’s like at other places, but I would imagine it’s in that range. What happens when you go for oral ketamine and so forth, I really don’t know what they charge, but I would guarantee that almost no insurance covers that. That would definitely be out of pocket, so I don’t know what the cost would be.

Kevin Pho: We’re talking to Jim Ellwood. He’s an anesthesiologist, and today’s KevinMD article is “The truth about ketamine: An anesthesiologist explains drug safety.” Jim, let’s end with some of your take-home messages that you want to leave with the KevinMD audience.

Jim Ellwood: I think the important thing is, don’t lose hope. If you have treatment-resistant depression, it can be very daunting. You sort of are set up for failure just from your mindset. You try medications, they don’t work, and you’re convinced that nothing is going to help. I think go the route. Try whatever’s possible. I mean, my doctor was great. We didn’t get anywhere with what we tried, but he stayed with me and said, “Look, let’s just keep looking if we can find a balance point.”

Also remember, even with a medication, the best thing is the combination. That’s been said many times before, but I think getting the help with the medication, getting the help of a therapist, now with telemedicine, thankfully, it’s an easier thing to do.

And more importantly, if you do decide on ketamine, be aware it is a powerful drug. It’s only dangerous when it isn’t used properly. If you decide to do it, make sure you’re doing it in a setting that is safe and that you feel safe in. Because a big thing that’s always mentioned is set and setting: going in with the right mindset and being someplace where you feel safe, not out in the woods tripping with your friends and worried the police are going to find you, or your friend has turned into a demon, or the squirrels are talking. So I think those are important things.

And then also, there’s still a stigma attached to it. I think it’s important for people who are experiencing it to come out and talk about it. And thankfully, I’ve been very lucky, and my chiefs of service have always supported me with my problems, and they’ve helped me get into sessions and find help. But I think that’s the big thing. It’s still awkward. It’s still hard to discuss, but try to realize it’s just one of those things. It happens. In many ways it’s like any other disease. There’s some malfunction that can have a biological origin, and it can be helped.

Kevin Pho: Jim, thank you so much for sharing your story, time, and insight. Thanks again for coming on the show.

Jim Ellwood: OK. Thank you.