Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, our discussion focuses on ketamine therapy in a controlled environment and our new suite at Northwestern Medicine. Joining me is Dr. Brandon Hamm. He's an Assistant Professor of Psychiatry and Behavioral Sciences in the Department of Psychiatry at Northwestern Medicine.

Dr. Hamm, it's such a pleasure to have you join us, and I really think this is such a hot topic right now. Before we get into the therapy itself, can you start by telling us a little bit about the evolution of ketamine and ketamine therapy, which has confused both the public and healthcare professionals alike in recent years? We've heard a lot about it in the media. How has it broke onto the scene in ways we might not have imagined?

Dr. Brandon Hamm: Yeah. Well, thanks for having me, Melanie. The ketamine, yeah, you're right, it's been an evolution. And certainly, there's different ways that it's gotten clinicians and the general public's attention based on that evolution. I mean, ketamine came out in the '70s as an anesthetic. And it had its pros and cons as an anesthetic. And predominantly, that was its reputation was for how it enables anesthesia.

However, about 20 years back, started getting a little bit of a look for what else can ketamine do in bench science. And so, there was a signal that this seemed to help with immediate response for depression in animal models. And then when this was looked at with human subjects, it looked to be the case that there's maybe a breakthrough treatment here where we can get some fast response for very strong depression presentations as well as suicidal ideations. Some things that really we're in dire need.

And so, the medication got attention. It was already FDA approved, like I said, as an anesthetic. And so, it could be used, but it was very early in the stages for what's our evidence base in patients for depression treatment. There was a little bit of a cart before the horse with that with some clinics with anesthesiologists being very comfortable using this medication. You know, starting clinics saying, "Hey, I see this depression response. I know how to use ketamine." And so, there's some early clinics doing this treatment really before we had the substantial evidence that we're now a lot later in history with that and in the buildup of studies and science and different clinicians and academics looking at this thing. And it turns out to be it's true the medication works very well for immediate depression and suicidal ideation response. And it also turns out that the medication and with the protocols that are used to get that treatment response ends up being very safe.

Part of the evolution as well is an evolution of a spectrum of stigma around ketamine, because ketamine also has a reputation for substance abuse. And this is something that it's not just restricted to club drug use, but ketamine particularly in European club scenes became a popular drug to get dissociative experiences around, you know, music. And for that reason, it developed a bit of a reputation as more of a thing that would be bad for mental health than good for mental health. And certainly, abusing ketamine is not good for mental health. However, each tool has its ability to be used safely and its potential to have side effects or negative consequences if used improperly.

And so, with ketamine, it turns out to be the case that we can safely use this medication in a therapeutic way when done correctly, which for our clinic is done with the evidence-based medicine approach that's informed by studies that have come out as well as informed by standards used by peer institutions, academic center, institutions that have ketamine clinics.

Melanie Cole, MS: Well, thank you for that. And as you said, it's a tool, yet another tool in your toolbox and in a controlled environment. That's so important to note. So, how do you evaluate and select patients for ketamine therapy and particularly, Dr. Hamm, those with complex psychiatric and medical conditions?

Dr. Brandon Hamm: It's incredibly common for folks that we see in our clinic to have complex mental health backgrounds. And, I mean, so ketamine is often not considered a first-line treatment for depression, anxiety, or for trauma experiences. It's a tool that people think about when other things that are more first line haven't been as helpful for them as they were hoping. So, often, folks that have trialed different treatment strategies have been living with these mental health struggles for quite some time, and they're looking for something that gives them a relief from suffering, that these other trials and treatment approaches just haven't given them thus far. And so, they're thinking, "Could this tool give me what I need?" So, that complexity is common.

That said, the evaluation that I've structured does focus very granularly on a mood disorder history for patients. It also looks less granular. I mean, there's only so much that you need to know or that would be appropriate to get into granularity regarding folks' trauma. But that's also an element that's important for just understanding where a person's coming from, and where their suffering's coming from. And I think the psychiatric evaluation, we aim to do a very comprehensive evaluation of that complexity of a patient's mental health history.

But within that, we also try and get a deep understanding of what's the drivers, what are the elements that contribute to the depression experience for this patient. And for a lot of folks, that's major depressive disorder episodes. For some folks, early life relational trauma has an ongoing impact on their mood. For some folks, their medical issues and grief or even vulnerable hormonal change times contribute to their depression experience. And so, getting a sense of, you know, what is the patient's experience with depression and trauma, and then being able to size up does ketamine seem like something that would be helpful for them and what else would be helpful for them? Those are the goals of the evaluation, and I think we're able to do that very efficiently, but also in a very patient-centered way in our evaluations.

The sizing up if ketamine's going to be helpful is a big part. But also, there are some people, it is not a hundred percent drug. So, it works very well. It's got good odds, but it also doesn't work for everyone. And so, in these evaluations, I also want to size up, what are the things that would be helpful alongside ketamine for the patient's mental health care, which can include things like psychotherapy, of course. And if this doesn't work, if we do a treatment trial and the patient doesn't feel better, what would be some next steps that we can immediately have in our back pocket to help the patient transition from sometimes the hope in this treatment, if they were very far along in their mental health care and they were really banking on this to do the trick. What's a good treatment plan that we can think of in advance.

I also like to collaborate with the patient's outpatient psychiatrist. Most patients that we see do have outpatient psychiatrists. Some folks have been doing mental health care through their primary care physician. But whoever the person that has been doing leadership for the patient's mental health care, we collaborate with them as well. And thinking about the role of ketamine, what are the questions they have? Are they comfortable with their patient going through this treatment? Do they have any other ideas about what would be next steps? That's all important for that initial evaluation.

Melanie Cole, MS: Dr. Hamm, as Northwestern Medicine upgrades its infusion space, speak about the new features and best practices that you're adding to enhance the patient experience during the infusions and the safety monitoring practices that you implement during that type of therapy.

Dr. Brandon Hamm: I'm very excited about this new space. I think it's going to be a terrific upgrade for patient experience. Honestly, our patients have been very happy with their experience with our current infusion space. we've designed it, and the experience and workflow to enable a good patient experience and patient control over and choice within their sensory environment with a layer of having very clear support alongside their infusions.

And so, I feel like we already have the patient able to make choices about their sensory environment and establishing a psychological safety environment. That said, the medical space, there are some things that are going to be enhanced with the new space. One is that the new space will have three infusion rooms that can simultaneously have infusions performed at. And that increases, of course, the appointment selection. So, it increases our access for more times, including for more than one patient if you have kind of around a similar timing for their infusion, if that's what works best for them in the week.

We'll have video in the room so that a nurse can monitor through a central room alongside, both the patient's vital signs, cardiac monitor, and the patient during the infusions. Currently, we have a one-room infusion suite. So, this enables more patients to get their treatment with a more convenient timing. Actually, for our clinicians and trainees, it also is a more efficient central hub for supervising the infusions.

In addition though, we're making strong efforts to optimize the space for patient experience with sensory experience and just a sense of overall comfort. We made an effort to try and demedicalize the environment while maintaining a good balance of medical standards. And so, you know, there's some ketamine infusion or treatment spaces that are very, very casual, more like a living room than a medical space. And we're trying to balance what makes a good patient experience while maintaining medical standards and safety standards. And I think we strike a good balance with that. Patients have choices they can make about the way that they feel most comfortable in their environment during infusions, with visual, auditory, smell, even tactile experience elements. And those are things that we are optimizing more in this new space, like with a projection screen for mindful imagery experience with projections on the walls that are peaceful, that people can do if they choose some more advanced lighting options, auditory options. And overall, it'll be a sleeker, more pleasant room experience for patients.

Melanie Cole, MS: So Dr. Hamm, because as we were saying in the beginning, there've been misconceptions, people weren't quite sure as this was coming onto the scene in a new way. What common misconceptions do you see among referring physicians regarding ketamine treatment, and how do you address them when you hear this, both from patients and referring physicians?

Dr. Brandon Hamm: I mean addressing them is kind of seeing where the person's coming from and responding to their concerns. Some concerns may be valid, and other concerns may be an opportunity for some education in the area where the person's a little less familiar.

I'd say probably three big areas. One is that there's a little bit of distrust in the addiction potential of ketamine and, I guess, the area there is that ketamine is something that can be abused. There are over-the-counter drugs that can be abused. And ketamine has mild to moderate addiction potential when used or abused a certain way.

These ketamine infusions that we do, the subanesthetic ketamine infusions at maintenance of every three to four weeks, that's not addiction. And so, at this point in time, we have good data demonstrating that this doesn't increase a person's risk of addiction to be doing it once every three to four weeks of anesthetic ketamine infusion. And so, sharing a little bit of that safety data as well as the, "Hey, what we're doing isn't the same thing as what's done when a person's using this on the street at high doses, with regularity at a concert or something like that. So, it's having a discussion with the person also validating their concern. We want to be thoughtful about the safety of our treatments.

Another area, I think, is just kind of distrust in ketamine as a treatment, because like I said, it was being used in a, private practice model in different ways or without a standard protocol. And it was kind of like what's going on in these clinics? Are they giving people good treatment or is it more of an entrepreneurial enterprise that's not as legitimate medicine? I'd say now, there's more legitimacy in understanding and visibility of the research done with ketamine to show, yeah, this stuff really works well. And it's safe and there's a little bit more glued together standards of practice. But I guess concern for patients displacing their trust in untrustworthy clinics what is an area that may come up for some clinicians.

And so, I think for, our clinic, I've had the approach of thinking that trust is earned rather than inherited. I think we do a good treatment service for patients. And I think that the clinicians that have referred patients and touched cases of patients that have gotten much better, we've earned some trust with them. And that's a bit of an internal thing for our system. But I think that decreases stigma over time in our system and in the clinician community here. We do have folks that are referred from outside Northwestern to our clinic. And I think they've been happy with the treatment their patients have gotten here.

Another element of misconception would also be that patients that are referred to ketamine. It doesn't have to be that they're the worst depression scenario you've ever seen, or that it's the hardest, most dire mental health crisis that you've ever seen. I think it's held out pretty long in a lot of cases as a treatment consideration as well as transcranial magnetic stimulation. These are treatments that have very high efficacy and some patients are really suffering. And they may trial treatments that seem very similar for many years. It often seems like ketamine or transcranial magnetic stimulation is something that can be considered a little earlier if a person's not made progress over time.

And so, yeah, I'd say one misconception would be that the side effect profile with ketamine and transcranial magnetic stimulation is very good. And these are treatments that are very safe and that patients tolerate well. And they're comfortable undergoing them. So, that's one area, is just reassurance and a little bit of education on this not being a Hail Mary kind of treatment. This is something that can be just a very effective treatment that can be considered for patients that other treatments have not given us adequate response.

Melanie Cole, MS: This is such an interesting topic, Dr. Hamm. There's so much to discuss. And beyond ketamine, speak briefly about other depression treatments like ECT or TMS. You mentioned a few a little bit that you offer and how you determine-- as you said, ketamine is not necessarily first line, so tell us just a little bit about how that works in some of the other treatments.

Dr. Brandon Hamm: Sure. TMS, ECT are other treatments for treatment-resistant depression or treatment-refractory depression. And they both are very effective treatments. TMS, the way this treatment works is that there's a series of magnetic pulse stimulation sessions done over several weeks. And over time, this actually increases activity and connectivity in the brain in a way that is a countermeasure to the way that the brain functions in depression. It's an astonishingly effective treatment and very well tolerated. Side effect profile is really just being able to tolerate that magnetic pulse sensation. Otherwise, just fabulous side effect profile. TMS is often considered in a similar timeline as ketamine for some patients. And it's a really a person-centered approach to seeing what is a best fit for one person or another.

ECT is a treatment that is the most effective depression treatment we have. That's why we're still doing ECT. It's been around for a long time. It is more reserved for cases where other treatments have been inadequate over time. It's often reserved for treatment when depression is severe or dangerous. But ECT is a fabulous treatment in that it has a best track record as far as efficacy. ECT can cause temporary cognitive side effects. And so, for some people, they may choose TMS or ketamine, which don't have those side effects, as an option to trial before considering ECT.

But Northwestern has a program where we offer all these treatments and these different treatments are best fits for different patients. And some of that is what's going on from a mental health diagnosis and history standpoint. And some of it is patient preference.

There's some other treatments that our Neuromodulation or Interventional Psychiatry Department are working towards right now, including vagal nerve stimulation. This is a treatment that also has a randomized controlled trial study with efficacy for treatment-resistant depression, and can work very well. It may be that some patients that feel ECT isn't a best fit for them, would be a good fit for a vagal nerve stimulator or some patients that maybe had ECT in the past and it worked for them, but they wanted to try something different, that would be an option for them.

So, the TMS, ECT, and ketamine are things that we currently have, but we're working towards innovating within our department and trying to expand our interventional procedural, depression treatments as well.

Melanie Cole, MS: Dr. Hamm, as we wrap up, how are you involving residents and fellows in the Interventional Psychiatry program, and where do you see this going in the next bunch of years, and ketamine therapy? What would you like the key takeaways to be here?

Dr. Brandon Hamm: One big message would be that these are very important treatments in mental health care. And our program provides education on and skills building on being able to perform these treatments for psychiatrists in training. And so, the residents have neuromodulation or interventional psychiatry rotations, where they're involved in all of these interventions from evaluations to having some engagement in the procedures. They're not the main doctors in the procedures to be clear, but they're learning how to perform them and it may play some roles in some of the treatments. We have fellows that have different interests and some fellows are very interested in getting some experience with ketamine or getting more experience than they had in the residency with ECT. And so, we make arrangements on a kind of interest-based basis for fellows to get more experience with these interventions.

That said, our program does have interest in developing an Interventional Psychiatry fellowship. That's something that there are a few places within the country that do have Interventional Psychiatry fellowships. And we think that that's something that we can build towards in the years ahead.

Melanie Cole, MS: Thank you so much, Dr. Hamm, for joining us today and really sharing your incredible expertise for other providers. 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.