Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today to highlight the Northwestern Medicine Ketamine Infusion Clinic is Dr. Brandon Hamm. He's an Assistant Professor of Psychiatry and Behavioral Sciences and Consultation Liaison in Psychiatry at Northwestern Medicine.

Dr. Hamm, thank you so much for joining us today. I'd like you to start by providing us a little bit of an overview of your experience in the field of mental health and ketamine infusion therapy. What led you to specialize in this?

Dr Brandon Hamm: Well, I gained interest in ketamine for mental healthcare when seeing the papers come out about some remarkable results with fast action, treating treatment refractory depression, some of the hardest folks to get treatment responses with. And I think a lot of physicians, broadly, but especially psychiatrists, were paying a lot of attention to what's going on here with this evidence with ketamine, and is it real, is it not real? It sparked attention of everyone, though, you know, some people became a little more interested in thinking about where's that going to go? And then, other folks were a little more dismissive or skeptical about. And I was probably in the middle, honestly. But my fellowship training is in consultation liaison psychiatry. And so, I'm seeing folks in the medical units, and I see some really hard cases of people in bad situations, things like metastatic pancreatic cancer, who are quite depressed and are in dire straits.

And there was one case I recall. I had this gentleman who overdosed on oxycodone with metastatic cancer. And he probably had a prognosis of about two weeks left. And it was just a matter of time. And that day, that pain was so bad that he just took that much. After he was stabilized, he said, "Ah, I don't have as much pain, so I don't want to do that today." And I wondered at that point, "Man, would something like ketamine get that guy a fast response so that he could just live out the rest of his life without a deep despair?" So, that got me a little more interested in it. And I guess it also helped that there was a lot more research done with this innovative tool. And so, there became a lot clearer evidence of the efficacy of the safety. There were more academic institutions taking on ketamine research. And of course, there were increased private practice clinics, then you started hearing more stories about patients' responses with ketamine, some people having significant benefits for their life. And so, it gained my attention, and I noticed that we hadn't had ketamine clinic here and was talking with folks in the department about that. And that was something that we were talking about for a couple of years. And there was a window of opportunity and we started to try and build the clinic.

Melanie Cole, MS: Well thank you for sharing that. What types of mental health conditions do you typically treat at the clinic? Tell us a little bit about the clinic itself.

Dr Brandon Hamm: The setup for the clinic is when a patient is referred by their primary psychiatrist, all the patients do have to have a psychiatrist that has determined that they are comfortable with referring the patient for ketamine infusion. So, we're not looking to be some side thing where the primary psychiatrist isn't in charge of the patient's mental healthcare and isn't aware of the patient using ketamine, having a ketamine treatment. But the patient is referred to me and I take a look at their medical background, the chart and see if there's any kind of clear contraindications that would be unsafe with ketamine or medication issues and also try and size up a little bit about diagnosis.

And then, if it seems like a person that could be a candidate possibly, then I coordinate them being scheduled for a clinic for an initial evaluation, which is about an hour and a half. It's a very formal evaluation that's very granular, looking at trying to nail down a mood disorder diagnosis. There is a lot of different presentations that end up being called depression, and not all of them are episodic mood disorders. And so, we try and get clarity then with a very formal and validated tool utilizing process to clarify depression level and mood disorder diagnosis and go over the more granular contraindications, aspects that would need to be navigated for a person to be a candidate for ketamine. Some people will need clearance from neurology or cardiology based on if they have a cardiac or neurological condition that's not an absolute contraindication. But there's some nuances to it that we would want to make sure we have the right expertise for those aspects, taking a look at it.

And I'm able to show the patient where the ketamine infusions are. And I also talk to them about, based on the diagnosis that is reached, what are potential options that maybe they hadn't considered as far as alternatives to ketamine, that would be potential things that if they weren't sure about ketamine as their next step, it is a more aggressive step for depression treatment, then they could consider further discussing some other options with their outpatient psychiatrist and they may say, "Well, I'm not ready to commit for ketamine right now. I'd like to try one of these other things first and see if that's helpful." But we can do consent for the ketamine infusions at that time and then schedule the next steps for ketamine infusions.

The way that works is that there is an induction and maintenance period. And this is a little bit of the setup that's used in electroconvulsive therapy. And so, there's more frequent initial doses with ketamine. And then, once you get the treatment response, you're able to space out more. And actually, the way ketamine works is that, if you just do a single infusion and a person has a depression response, that only lasts for about four to seven days. However, if you do this induction period, it improves the longevity of the treatment response. And the average patient would last for three weeks and so, will be getting an infusion every three weeks. So, we've got this induction period of six infusions over three weeks, so twice a week. And some patients may need an extra one week of the twice-a-week infusions.

But from there, folks would be going to once a week if they maintain their depression and suicidal ideation improvement, then they would go to once every two weeks and then spaced apart to the once every three weeks. Some patients can last once every four to six weeks with their depression response. And I guess, the other aspect of that is we do have some availability, but we're trying to build a clearer way to get people into integration therapy to, alongside their infusions, integrate some of the things that they have maybe processed in their ketamine infusions, because it's evident that there's an increased learning capability that's in the window probably seven days after the ketamine infusion. So, some patients can gain major insights about cognitive distortions, ways that they're defensive, ways that their self-image is inaccurate or too negative, and trying to concretize and make those kind of insights more permanent rather than fleeting, is one of the goals with psychotherapy, that's ketamine-assisted psychotherapy.

That's the general structure of the clinic, is the initial evaluation, the kind of safety, the candidacy with clearance if needed. We do get a urine toxicology, at the beginning, and a pregnancy screen at the beginning. And if there are other labs or work if it's needed, that kind of thing. And then, it's the initial six infusions and then hopefully spacing out to about every three weeks fairly quickly in the maintenance period.

Melanie Cole, MS: Thank you for giving us such a comprehensive overview of the clinic and how ketamine therapy works. And can you speak just briefly about metrics or criteria that you use to measure the success of the therapy itself?

Dr Brandon Hamm: We're using many metrics that we're tracking, and some of these we will likely be utilizing in academic work. But the depression aspect, there's two validated scales that I use on the initial evaluation. One is Montgomery assessment, the MADRS. And then, there's a self administered-- I'm just going to give the acronym because otherwise, I know I'll get one of the words wrong, the QIDS, for depression severity. And these are actually two metrics that for depression are validated for high-frequency testing. And so, some of the depression tools that are validated are not intended for multiple-times-during-a-week testing, these ones are though. And so, MADRS enables me to do a clinician-administered size-up of the depression severity, and then the QIDS is a patient-administered self-report. And I would have both of those scores at the initial evaluation for a severity index of depression. And then, we would track the QIDS, a person does it before each infusion.

There's several other scores that we're looking at, though. The NIH has PROMIS measures that are validated. And currently, the ones that we're looking at, they're question banks, they're very fast for patients to fill out. They actually are able to fill them out before they come in for their visit. I sent out the questionnaires through my chart ahead. There's a meaning and purpose, depression, anxiety, and social isolation. We're trying to get the positive affect one built out too. But these would be things that are tracked on each visit before a patient's infusion.

Additionally, there's a scale that is the Watts Connectedness Scale that we are tracking for each visit for a patient. And this is an area of depression that's a little overlooked. It's not built into our normal depression evaluations. But when you look at the phenomena of experience for patients with depression, they're feeling disconnected from themselves, from others, from just like the environment, community, cosmos, those kinds of things. Those are major impacts for the meaning of the depression experience and what's so intolerable about it for patients. And so, we're actually tracking that for each infusion visit for patients. And that'll be one thing that we'll be studying in the clinic as well.

We do some of the other metrics. I do a personality inventory for DSM-5 to get a sense of the patient's personality traits on that initial evaluation. When we are doing infusions, there are a couple extra validated tools that we use for safety screening. Patients can get dissociation during their infusion, which isn't necessarily dangerous or bad. But we need it to be to a low level and largely gone before they leave. And so, after the infusion is completed, we do a CADSS dissociation scale that's been validated. It's the one that's commonly used, the vast majority used in ketamine literature for this. And so, we check that at the end of the infusion. If the patient is dissociated at the time of the completion of the infusion, there is a 30-minute observation period that's required after the infusion's completion. And if the person is dissociated, after they finish their infusion, then we double check that at the end of that 30 minutes. If they're still dissociated, they would need to wait a little longer before they leave.

We also do a bCAM for a screening tool for delirium before they leave as well. And so, we have a very formal process for clearing the patient as cognitively safe to leave the clinic at the completion of the visit. Our protocol also does require a patient to have a chaperone to transport them after the procedure, similar to if a person got a colonoscopy at Northwestern.

Melanie Cole, MS: Dr. Hamm, this is such a fascinating topic and field that you're in. And ketamine's been in the news recently surrounding Matthew Perry. Can you please tell us a little bit about what you think of this?

Dr Brandon Hamm: The first thought was it's a tragic death. And it looks like there was publicity about substance use issues, I wasn't familiar with that. But I did see the headlines on that and read the New York Times article, and peeked a little bit more at things, given the ketamine involvement. What it looks like is that he had struggled with some very strong addiction issues, was a two-pack a day smoker, but also was, at times abusing like almost 80 Vicodin a day. So, he had very strong addiction issues that he struggled with for a long time. When he was in heavy addiction, he would binge on things.

And it looks like he also struggled to be honest with folks about whether you're sober or when he would abuse things. And he would try and hide evidence of what he was using. Apparently, he liked to use drugs in his hot tub. And that was Kind of the most pleasant way to do that for him. And he had been telling people he was on the clean streak. It seems there's not a whole lot of content I could see about what his actual ketamine setup was, but he had some experience with ketamine. It sounds like he probably had a ketamine clinician, and that he had an infusion perhaps a week before the event. The autopsy found that he had levels of ketamine that would be twice the normal levels for sedation, for anesthesia. And that means a few things to me.

One, that's not levels that would be done with ketamine infusions for treatment of refractory depression. So, the levels are higher than any patient we would be seeing would get. In a sense like they were twice as high as patients for sedation would be getting under sedation for anesthesia for a procedure. So, it's quite high levels. He would not have walked into that bathtub with those levels. He had to have taken ketamine that, I assume, it would have been oral at high doses to achieve those levels. If he'd had those levels before he got into the bathtub, he would not have been mobile. He'd be in the sedation state. So, it seems to me that he had some recreational ketamine abuse in the hot tub. Was that for suicidal intent or was that just addiction behavior, abusing the substance that I don't know if the substance that he used was given to him by a clinician or was on the street? But I guess the big picture is that representative of the risks of doing ketamine infusions for treatment refractory depression.

Melanie Cole, MS: Well, thank you for discussing that and clearing it up a little bit. So as we wrap up, how do you see Northwestern Medicine's program developing over the next several years? Do you see this for a broader patient selection? Do you see broader criteria or exciting research? Give us quick overview.

Dr Brandon Hamm: I think largely all of the above. We are building our program and trying to expand our access and capacity for that for more patients. We are following the literature on what is effective what indications or different patient psychiatric issues are well-treated with ketamine. And there are several leads on things outside of major and bipolar depression, which are the things that we would be doing ketamine for right now. There are other areas like PTSD, substance use, cocaine, heroin use, that are getting some research. There's some research with even borderline personality disorder and ketamine. This is young research. It's smaller studies. Methodology of the studies isn't as high. And there are going to be some early adopters to go ahead do those things. There are patients that have reported negative experiences with these conditions as well. So, we will see if it does become clear that this would be a more standard of care to provide ketamine to some of these other conditions. We would consider expanding to that here as well.

We do have several research studies that are either under construction here or are going for the Ketamine clinic. A few of those are looking at different side effects of the ketamine for us to better understand things with the medication. Some of those are patient experience-related studies. One of the studies, we got a small grant for a pilot study for randomized controlled trial looking at a psychology modality for augmentation of the ketamine infusion, with the hope that we could see if this could increase the longevity of treatment response or instead of the person being once every three weeks, if they can maybe be more likely to make it to once every four to six weeks.

We're also interested in collaborating with some of the other departments at Northwestern. There's a music theory and cognition professor at the Evanston campus that I'm collaborating with as well. And so, I think there will be a lot of exciting research with the program. We did just get our clinic kicked off and we're planning to get all the research activated now as well, but have been working on the infrastructure to optimize that.

Melanie Cole, MS: Thank you so much, Dr. Hamm, for joining us today and sharing your incredible expertise on a topic that not a lot of people understand. So, thank you so much. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/psychiatry to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.