Dr. Alex Danvers (Host): Welcome to Behind the Miracle, the Sierra Tucson podcast. I have with me today, Dr. Irfan Fauq. Irfan, how are you doing today?

Irfan Fauq, MD: Doing well. Thank you for having me.

Host: Yeah, I'm really excited about this interview. I'm really excited to talk to you. You're one of the providers who I get a lot of really positive feedback about. I know a lot of patients find you to be a really big help. And I also know that you're really passionate about continuing to learn and grow as a provider and kind of dig deep into the science. And so I'm really glad that we'll be able to talk today about the use of esketamine and intramuscular ketamine at Sierra Tucson.

Irfan Fauq, MD: It's very kind of you to say, but I have to give the credit to the patients. They do all the work.

Host: Yeah, good. Yeah. That's a nice attitude, but I'm sure that there's something that you're doing there. I don't know if you know this, but I think fellow Dr. Jack

Irfan Fauq, MD: McClain,

Host: has told me that he sometimes compares how many positive comments he gets to how many positive comments you get. I don't know if that's a one sided competition or not.

Irfan Fauq, MD: I'm going to have to talk to Dr. McClain about that.

Host: Yeah. So let's just start with kind of what's your backstory. What got you into medicine?

Irfan Fauq, MD: It's not that much of an interesting backstory. I was born in Pakistan and, but I grew up in Florida, where I developed a deep love for soccer and hip hop. Education was prioritized in my household, so there was a lot of encouragement to be, you know, a lawyer, a doctor, an engineer.

It was pretty common. I ended up in medicine, and it was in medical school and during some research projects around that time where I developed an interest in psychiatry.

Host: Oh, that's great. Yeah. I know that on your bio on the University of Arizona webpage, it mentions that you like hip hop. And, I wondered about that. It started, early.

Irfan Fauq, MD: That's where it's from, that's where it's from, yep.

Host: When did you first hear about using ketamine or esketamine, Spravato treatment in psychiatry?

Irfan Fauq, MD: You know, I'd heard whispers about ketamine having some benefit in the mental health treatment space all the way back in medical school. And this is, you know, end of the noughts, around 2008, 2009. But it really wasn't until I was in residency when I formally looked at the information available. And was pretty encouraged about the results being shared, and I'm sure we're going to dive into that later on.

Host: Just to kind of continue along that line, was there anything that made you particularly interested in ketamine and escetamine where there may be patient cases or sort of research conferences or anything that kind of pushed you in that direction?

Irfan Fauq, MD: The origin story of ketamine is pretty interesting in my opinion. This is a medication that was initially developed as an anesthetic and found to have a lot of utility and qualities that separated it from other typical anesthetic agents, in terms of how and where and, and what it could be used for.

It moved beyond operating rooms and kind of combat situations and found to also be helpful for other things like its utilization in veterinary medicine. As I mentioned, there were whispers about its utility in other fields like pain management and psychiatry. Honestly, I think I'm just a sucker for this kind of story. An agent that was developed for one purpose, only for it to be shown that it can have a meaningful benefit in another direction; oftentimes unexpectedly.

Host: Yeah, that's actually a very cool backstory. I think probably a lot of the current conversation around ketamine is around sort of the non medical use of it. But it's really nice to remember that it, this is something that came out of anesthesiology and it has always had really valuable medical uses and that those uses can continue to be explored.

So I don't know, maybe it's good to stop now and take a minute and go into what is ketamine, what is esketamine, what is kind of intramuscular ketamine and and what is it used to treat?

Irfan Fauq, MD: Absolutely. Yeah. So ketamine, it's a medication that for a long time, like I mentioned, was used in situations where you need to conduct procedures under anesthesia. It was unique as an anesthetic in that it could rapidly get people in an anesthetized state, but still retain one's airway. So utilization in non traditional settings was pretty prominent.

You know, think emergency situations, combat situations. In addition to anesthesia, we've seen it used in pain management as a fairly potent analgesic. In some cases, it's also been used to lighten the burden of those taking kind of heavier, complex opioid regimens. In more recent times, we've seen its development within the space of certain types of psychiatric illness.

And without getting too lost in the weeds, ketamine itself, it's a mix of two different types of ketamine molecules. And as ketamine was developing its kind of growingly positive, reputation in psychiatry, esketamine was then developed by the FDA. And esketamine basically took one of those ketamine molecules and then isolated it.

And in February of 2019, the FDA provided an indication for treatment resistant depression, which is defined as failing to respond to adequate trials of two or more antidepressants, and major depressive disorder with suicidality. So looking more broadly at the literature, ketamine's benefits have also been noted in other cases, related to post traumatic stress disorder, obsessive compulsive disorder, substance use disorders, bipolar depression and various forms of eating disorders. But that data is ongoing, and we're still collecting that, but it does seem quite promising.

Host: Yeah, that sounds a lot like something that you know in my neuro department, we use TMS where there's a lot of early research showing hey, this is really good for treatment resistant depression. It's an alternative which I think is something that's really needed for a lot of people going through really serious depressions. And then now there's even more research coming out as it's being applied to other disorders and maybe the case. It's also waiting for FDA approval as of now for other indications.

Irfan Fauq, MD: Absolutely. In fact, our closest university, University of Arizona is exploring how to use agents in this space for the multitude of other disorders that I previously mentioned.

Host: Yeah, so what kind of patient profile do you think might benefit from esketamine or intramuscular ketamine treatment?

Irfan Fauq, MD: The patient that would benefit most would be, we see it all the time here, it would be the individual who has tried a lot of conventional approaches, especially pharmacologically, to treat their mood, but really haven't been able to find that sense of sustained wellness and functionality that, you know, obviously every one of us deserves.

The patient who looks at life and struggles to see hope in being able to continue, that's the patient who might benefit from this kind of treatment. And as we're able to collect more data, there may be an expansion of the types of cases that the treatment might be considered for.

Host: I think that that's a really hopeful message that there's this alternative treatment that people might not be as aware of. How have you been using esketamine here at Sierra Tucson?

Irfan Fauq, MD: So we've been using esketamine, under the brand name is Spravato. It's delivered through intranasal cartridges. We've been using this medication at Sierra Tucson for its previously mentioned indications, uh, for the better part of the last two years. There are generally positive responses that we're seeing in patients, and that's allowed us to further consider how we can develop a more robust program to offer this medication or its parent medication, ketamine, for those who would benefit most from it.

Host: Yeah, that's great. And I know I've heard a lot about this from the patients and from the therapists and other providers here that this really seems to help people turn the corner. When we talk about sort of expanding this, we've been talking about adding intramuscular ketamine. What would that do for treatment here at Sierra Tucson? How would you add that into your sort of tool belt?

Irfan Fauq, MD: We would typically use the intramuscular formulation of ketamine for the same indications; treatment resistant depressive conditions, as well as depressive conditions that are predominantly characterized with suicidality. We will consider its use in those that suffer from some trauma syndromes as well, which are often those same patients that have been struggling with severe depression, suicidality, and basically diminishing returns from current treatment approaches. I wanted to say though, there's a difference between IM ketamine and intravenous ketamine in terms of the delivery method, but the actual chemical is the same. It's just the delivery method is different. So with intravenous, it's typically delivered as an infusion, over a certain period of time.

And, the intramuscular ketamine is delivered as injections as, discrete quantities. But essentially we are still utilizing the same chemical, ketamine that a lot of people have heard about. In the outpatient setting and other levels of care, they might use infusions of ketamine rather than intramuscular ketamine, but, the data is quite consistent across the different formulations.

Host: Yeah, that's really good to emphasize, right? I think if somebody maybe has found good success with ketamine in the past and they were thinking, hey, is this the same type of treatment that I'd be able to get at Sierra Tucson? Essentially, it's yes, right? This is the same chemical, it's just a different delivery form. So, what do you think benefits are for, either Spravato, esketamine, and IM ketamine? Like sort of over what we currently do, when we added this to the repertoire of techniques we use here at Tucson. What benefit did you start seeing?

Irfan Fauq, MD: I would say one of the biggest draws is that it is rapid acting, where promising results can be observed in some cases as early as after the first dose. Instead of waiting several weeks like with other medications, this is an intervention that can be used in more acute or subacute time settings, and potentially ideal for treatment settings like ours.

Other potential benefits include this medication being one that has very few drug drug interactions and generally doesn't carry many barriers, although there are some, when it's used in patients with more complicated medication regimens that one might associate with the treatment of severe depression.

And then additionally, its side effect profile in itself tends to be quite well tolerated.

Host: That's great. Yeah. So I think, just to sort of summarize back to you, I know that you know this, but, for my own comprehension, there's this fast acting action and then there's this element that doesn't really interfere with other medications. Right? So if you've got a regimen that works for you, you don't necessarily have to go through a lot of changes. There can be periods of buildup or withdrawal from medication. So you can just sort of do this more quickly.

Irfan Fauq, MD: Typically, right, there are some exceptions to the rule, but even those regimens can be modified so that this medication can be delivered and that its efficaciousness can be felt fully.

Host: Are there any drawbacks that you see to the treatment?

Irfan Fauq, MD: I would say just like with any other treatment, nothing is perfect. Even with careful selection of those who might benefit the most from this operating approach, sometimes we won't see the positive shifts that were hoped. This might be due to a variety of different factors, which can be troubleshooted on an individual basis.

Just like with other treatments that are considered fairly novel, sometimes expectations and hope can outweigh results, especially in early adoption. Which can, you know, if you think about the patient, it can kind of set them up for disappointment just in and of itself. So having a meaningful discussion around managing expectations is key.

The actual ketamine experience can be jarring for many, where a feeling of a lack of control from being acutely under its influence can be difficult to tolerate for some. Again, a discussion around expectations, very important. And finally, this isn't a treatment for everyone. And there are conditions in the psychiatric space that would prevent its consideration as a treatment option, so that needs to be considered as well.

I would love for this to be the panacea that we were all looking for, but our search continues.

Host: I think that setting expectations is a really important thing. I know a lot of people take antidepressants, but evidence suggests depending on the study, maybe only 40 to 50 percent of the people who take it actually see benefits. And so that leaves, in some ways, a big hole in coverage and a big gap in terms of what's the next step.

And we don't need to have a magic bullet as long as we have other possible next steps, right? And so this maybe helps to kind of fill that gap even if it's not always the right answer.

Are there any types of patients you would recommend not get the treatment?

Irfan Fauq, MD: In our program, we do have exclusionary criteria that would rule out certain cases for consideration. Usually they center around whether they have some discrete medical issues like certain cardiovascular or neurological risk factors, whether there are some psychiatric presentations that wouldn't benefit from this type of treatment, or if someone's pregnant or lactating. Or if they've demonstrated an intolerance to this medication, whether that's through hypersensitivity or allergy, in the past.

Host: Okay, so it sounds to me like that's something that really, through a careful physical exam, maybe some blood work or maybe some other, history, you could kind of rule out, but it doesn't sound like it's like, oh, only certain types of depression. It sounds like, this is really something that a medical appointment is needed to figure out for you, but it's not something that maybe you can sit at home and be like, oh, I've got this type of depression, and I can figure it out that it's going to be good or bad.

Irfan Fauq, MD: You know, there are certain types of depression that have features that may not be conducive to this. If someone experiences perceptual distortion, psychotic symptoms, with their depression, maybe this is something that needs to be reconsidered in terms of considering ketamine.

But I would say for the vast majority of people, I'm looking at kind of medical risk factors. I'm looking at treatment responses in the past, should they have had this. And then if they have other psychiatric elements that really might not be benefited from this particular intervention.

Host: How do you feel that this kind of treatment integrates with the other modalities and treatments that we provide here at Sierra Tucson?

Irfan Fauq, MD: I believe ketamine therapy is a natural addition to the armamentarium of mental health treatment approaches that we have here at Sierra Tucson. There is a central theme that's woven through all of our treatment modalities that attempts to create symptomatic remission, prevent future episodes, and improve overall quality of life.

And I think it also shows that Sierra Tucson is willing to adjust and adapt its programming with the latest literature coming out on how to best treat those who suffer from mental illness, especially those who seem short of hope given their mental health journey.

Host: Yeah, I think that's actually something I've really enjoyed about my time here at Sierra Tucson is it does seem like we're willing to embrace new programming, embrace new treatments. And so I think, it's nice to see that we're having success with this esketamine treatment, and so we're kind of building up into a larger program. Do you think there are benefits or drawbacks particular to Sierra Tucson or to this type of big residential facility?

Irfan Fauq, MD: Wen you look at the data around ketamine therapy, you'll see a lot of graphs and score reductions indicating rapid relief from challenging symptoms related to depression and suicidality. But we also see an agent like ketamine being able to induce a degree of introspection and amplification of one's subjective consciousness for personal growth.

And that can lead to inner healing, if not better insight to make that growth. We see how it can make the work someone does in therapy feel more impressionable and enduring. And, an agent that assists with those things, and can potentially see benefits within days versus months, is a natural fit for a program that is time limited, intense, and wraparound, like Sierra Tucson's residential program.

Host: I really appreciate that answer, and, I hope that I didn't ask it in a leading way because that was really something that was on my mind as I was asking it. You're obviously the expert in this particular treatment, but one of the things that makes sense to me intuitively about this is that, if you're having these kind of deep insights, it might be easier to capitalize on those while you're also getting, a lot of deep talk therapy, a lot of group therapy, a lot of time sort of apart from your normal life where you can reflect, more deeply. You just mentioned that this type of treatment where it's a short course, right? You take ketamine for a limited period of time. Typically, we have patients here at Sierra Tucson for four weeks. And I guess a course of ketamine treatment might be four weeks here, might be six weeks other places. Do you think that this tells us something interesting about the mechanism of change? Is there something that's different about treatments, or different about the type of healing that goes on in treatments that are shorter and maybe insight based?

Irfan Fauq, MD: A lot of the studies, particularly when you look at those where they use intravenous infusions or intramuscular injections of ketamine, they've looked at what effect one dose versus more would have. Typically, the more would include around six doses over a two to three week period. Esketamine is usually prescribed in the form of an intranasal delivery method.

Other oral formulations like lozenges or trochees have also been used. While there's a loose structure of what a ketamine course typically looks like, often involving up to six doses, it's not atypical for patients to receive maintenance doses. Essentially doses that are delivered over a more chronic setting, usually on a scheduled basis that has been discussed with their psychiatric provider, such as once a month or every couple of months following an initial treatment course.

If you look at the data, I've seen cases of people being on maintenance schedules for up to 24 months. Now the question around mechanism is an interesting one. Often, researchers will dive into specific mechanisms that might explain how the benefit of ketamine for the treatment of various mental health conditions are explained.

There are some ideas around specific mechanisms, however, research is ongoing regarding specifics. In the most optimistic sense, when looking specifically at resistant depressive conditions and associated trauma syndromes, ketamine allows for a break from that usual mindset that sets the trajectory for illness.

It allows the individual to consider different views, and invite a degree of flexibility towards new beginnings, while being less encumbered by the challenging, intrusive mental exercises and rumination that those who suffer from depression often have difficulty releasing themselves from. There is registration to what makes us feel connected and whole, and something that is often absent in those that suffer from these types of affliction.

Host: Yeah, I think that's a really interesting answer because it touches on a few different pieces. One is this idea that maybe with other antidepressants, like an SSRI is often given in the first line, it's kind of expected that you'll be taking it ongoing for the foreseeable future. And, that can be difficult for patients, it can be difficult for patients if, especially if they have side effects. But what you emphasized to me, more so than I thought you were, is that, with these treatments, esketamine, and, intravenous or IM ketamine; it's not just one dose, you had your moment of insight, your aha, and you kind of move forward. You often do see a trial showing, it sounds like benefits from more than just one dose.

Irfan Fauq, MD: Absolutely. In fact, they've looked at head to head studies, what is the effect of one dose of ketamine versus six? And you'll see that the impressionability of the therapy that's being offered at the time is far more deeper, far more enduring. The durability of response is also extended, between the two different approaches.

While a single dose has been shown to have its own benefits, especially when it comes to suicidality, when it comes to the insights drawn and the changes that need to be made in one's life to move forward; definitely having a multi dose course would provide someone with the platform to potentially reach that outcome.

Host: I think the other piece that I just want to emphasize in your answer is this idea of kind of, maybe habits or patterns of thought that you're talking about where, it sounds like one way to conceptualize this is people get stuck in maybe a cycle of rumination. And if you of can get kicked out of that cycle, kicked out of that loop, then you have this opportunity, to start to learn a new pattern, You're not stuck in that same pattern that you keep getting drawn back to. You get into this place where you're like, well, what other patterns exist? You know, what other possibilities are there? And that's where you can start to build a positive future trajectory.

Irfan Fauq, MD: Absolutely. It's almost like if you can take a break from all those depressive gremlins pulling at your shirt and at your pants and kind of pulling you back; if you could just release yourself from them even for a momentary window; it just allows for deeper understanding. Like I said, deeper impressionability of the therapy being offered

Host: I think ketamine is kind of interesting because it's part of this new movement of consciousness altering drugs that are being used in psychiatry. But, do you see any connections between ketamine treatment, and other medications like psychedelics or MDMA, which are currently in clinical trials for treating psychiatric disorders?

Irfan Fauq, MD: While ketamine and those other agents in the psychedelic category, whether it's psilocybin, DMT, LSD, MDMA, among others, there's certainly differences, whether that's in mechanism or in utilization. But it does appear that the psychedelic space and its potential benefit in treating certain psychiatric conditions is quite promising. And that's creating a groundswell of attention and interest on what that actually means on a functional level, on a treatment level. I am aware of advanced trials, and I'm sure you are as well, that are in late phases evaluating the safety, stability, and benefit of psilocybin and MDMA specifically.

We may hear of those results fairly soon, as early as next year regarding potential indications and how that may be applied.

Host: It does feel like there's this kind of groundswell, like you're talking about of new approaches. And, it does feel like maybe minds are being changed a little bit about the utility of these substances for helping heal people, which is nice. And I think, one thing probably the two of us have in common is that we are really into the data. So we're, cautiously optimistic, but wait until the data is out to do anything.

Irfan Fauq, MD: Absolutely. I need proof.

Host: So I mean, this leads a little bit to another question about, maybe a broader take or opinion on mental health and psychiatry. Do you think that ketamine, is going to just continue to grow in popularity in the coming years? Or do you see it as something that kind of remains like a niche tool for people who have a really specific problem.

Irfan Fauq, MD: I'm going to hedge. I'm just going to say it's really hard to say. You know, it's not uncommon for the excitement of a shiny new intervention to bolster the public and professional impression of it, even before meaningful endpoints around efficacy have been established. Ketamine therapy within psychiatry seems to be one of the first of several agents that may be able to provide an alternative treatment approach to those that are suffering the most.

So far, the data is very promising, but it needs to be tempered with a certain level of cautious patience as insight and strategies are further developed and adjusted to be able to utilize this type of treatment in the most effective way possible. That said, it's a really exciting time for psychiatry.

Host: It feels like a really exciting time for psychiatry. And I actually am really glad to hear your take being more cautious, because I think certainly what I've heard in my reading and, listening to podcasts and interviews and things with people, one of the takes that I've heard from a lot of thinkers is in the 60s, there was this rush towards using substances that maybe wasn't tempered, that was a little bit over enthusiastic and that was sort of saying this is going to change the world. This is going to be revolutionary as opposed to let's take things one at a time and really work through the evidence in a careful way. And, it seems like this time around, as we're talking about these as treatments, the scientific community is being a lot more cautious, a lot more measured. And that, ultimately, from my point of view, from a scientific point of view, makes me feel like, oh, we're going to get better data, we're going to get more solid recommendations that are specific and that are trustworthy, and not just sort of this enthusiasm for a panacea.

Irfan Fauq, MD: Absolutely, absolutely, 100 percent agree. And then, not to be too political, but I have to mention, the war on drugs just really set this whole process back. But it's exciting times though, and I genuinely look forward to how we'll be able to utilize these new medications, to, like I said, help, help those that need it the most.

Host: And keep getting you all those positive reviews that make the other doctors envious.

Irfan Fauq, MD: I really got to talk to McClain.

Host: All right. Well, I think that's a good place to wrap up. Dr. Irfan Fauq, it's been a pleasure. Thanks for being on Behind the Miracle.

Irfan Fauq, MD: Thank you for having me. And, I look forward to hearing future episodes.