Psychiatry & Psychotherapy Podcast - Cancer: Depression, Anxiety, And Hypoactive Delirium - A Dive Into Psycho-Oncology with Mona Mojtahedzadeh, M.D.

Episode Date: March 5, 2020

In this week's episode, we sat down with Shawna Chan, Mona Mojtahedzadeh, M.D., Salman Otoukesh, M.D., David Puder, M.D. and discussed different aspects of mental health in humans bravely facing cancer. Below is a link to the notes which go beyond the podcast episode in content and depth and hopefully equips you to have more empathy, compassion and knowledge. By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Hello and welcome to the Psychiatry and Psychotherapy Podcast. I'm here to talk about getting rid of burnout, increasing job satisfaction, and feeling like an expert in what you do. One thing that created a lot of burnout and angst for me was trying to get continued medical education right at the last minute. So why not join the CME membership and do CMEE while listening to this podcast? Go to Psychiatrypodcast.com, sign up, sign in, take the test, and the certification is email to you in seconds. Welcome back to the podcast. This is going to be an episode on PsychoOncology. So kind of like where psychiatry meets oncology.

And I have some amazing guests with me today. I have Shauna Chan. She is a fourth year medical student at UCI who interviewed with me for psychiatry. And then subsequently we decided to do an episode together. She was interested in psychoancology. And I also have a graduate of Loma Linda psychiatry residency, now a graduate of USC, C&L. And she is now working as a psychoancologist, as City of Hope. Mona.

Mojtahed, Zadeh. Mourch Ta'et Zadeh. Does that sound good? Okay. And I actually have her husband, who is an oncologist, a stem cell, bone, marrow transplant physician at the City of Hope. So he did internal medicine and then oncology and then subspecialization. Salman Otukesh.

Salma Otukesh. Dikish. It's so good to have you guys. Thank you. Thank you. We're so excited. Mona, you were one of my favorite residents that's come through in a while. Am I allowed to say that? Other people are going to be like, oh, am I not the favorite? No, you said one of the favorites. One of the favorites. You can have like thousand favorite residents. And if you've heard the episode that we did on estrogen and progesterone, which someone actually just sent me a message yesterday thanking me for like the nuance that was a part of that episode. That was an episode that Mona was a part of.

And so I'm excited to have you guys. We are so excited to be here. I was telling Salman in the car while we were driving that, you know, it's just very energizing to come to your podcast, knowing you personally because you were my attending and then knowing that you come from Loma Linda, the whole energy, enthusiasm, the good deeds behind it, I just fall back in the vibes immediately.

Every time I listen to the podcast and what we were driving here. Oh, that's fun. That's fun. Yeah, so I'm maybe just start, because I don't think a lot of people know what a psychoancologist does. So maybe just kind of share what that looks like. So we really like any other consul service, you know, what I am doing at City of Hope, which has been a really gratifying experience so far, it's inpatient and outpatient setting, console service. We work in a multidisciplinary team and most of the population that we see there are cancer patients. what I see that has been impressive for me working there most has been that the whole idea of whole person care that I try to carry with every patient encounter,

I see that very much implemented there with every, every, you know, service that sees for all those patients. but also just seeing patient also as a broader picture in a context of their family, when the patients are impacted by cancer, usually the whole family members or beloved or close to people, they are all impacted. So what we do in the psychoncology field, I don't consider myself psychoncologists yet. I've started working there like since mid fall last year and I've been learning. It's like an ongoing experience of learning. But it's very beautiful because you just see how the wide range of areas where you can be impactful in that patient's life and not just by treating the symptom or the symptom or the disease that you are being consulted for.

That's beautiful. Yeah. I'm so excited that you pursued your dream, right? Because it's just kind of like a dream. And it's kind of fun because your husband's an oncologist. Yes, yes. And so you have that connection. Actually, I'm the lucky one that I have the Mona in my life and my actually medical life

and the personal life because at the end of the day, you know, when I see a patient with the cancer, cancer by itself bring a lot of burden to the patient and the family. And City of Hope, there is a very famous sentence. and the city of hope everywhere, you can see that they are saying that in the road of healing body, the art is not destroying the soul. So having said that, most of the patients coming to us, for example, for the stem cell transplant,

the process of getting into it has a lot of pressure on them. And after they receive the stem cell transplant, because it's a kind of new life for them, exactly like a baby, even, even the vaccination should be exactly like a newborn baby. And at that time, we do have a very specialized team. And one of the main person of the team, of course, is a physician transplant. But the second person is the specialized psychiatrist.

That they are in close contact with the patient almost every day, daily basis, because they're going to stay in the hospital. And then nearby after that for almost 100 days, to make sure that everything is right. And they should come to our center and see us and psychiatrists in most of the time, like twice weekly. Wow. And I want to jump in here.

And there's this whole division of supportive care, supportive care division, where it includes psychologists, social workers, psychiatry, pain, palliative. And so the whole service, you know, is like hand-in-hand collaboratively working. Sometimes psychiatry gets involved, sometimes not, but it's just beautiful to see that, you know, that collaboration from very direct clothes.

Yeah, yeah. With cancer patients. Yeah, so I want to get into kind of some of the pearls that we can, you know, give to a provider that is seeing someone who's struggling with cancer. And so I was thinking we could start with kind of talking about some of the some of the differential diagnostic thoughts around you know is this depression is this normal grief is this hypoactive delirium are these cancer symptoms are these symptoms of the

medications that are used to treat cancer and there's a lot there right we could probably just talk about that for six hours so we'll probably just touch the tip of the iceberg and and give some of the big kind of things so maybe i'll have Shauna start, what does depression look like for cancer patients? So I think depression is a very interesting thing to look at within that patient population because there are certainly symptoms like anorexia, insomnia, fatigue that could be due to their treatment or due to the recent diagnosis versus an actual clinical diagnosis of depression. So there are some different approaches to diagnosing whether a patient has depression.

There's the inclusive approach that counts any of the major depressive disorder criterion, regardless of whether it's due to the medical condition or a psychological cause. And this approach can result in falsely elevated rates of depression. So there's also the exclusive approach that excludes anorexia, fatigue. However, this then results in reduced sensitivity for detecting depression. And lastly, there's also a substitute of approach that excludes somatic symptoms related to somatic illness. So it'll exclude fatigue, weight loss, psychomotor changes, and replace that with cognitive affective symptoms, such as irritability, tearfulness, feeling punished. And the interesting thing is,

I guess, between these different approaches, it's been found that they each have advantages and disadvantages, and ultimately it's hard to decide which is the correct approach for every single patient. Yes. In the recent years, there has been increased in prescription of antidepressants in cancer patients and that has not necessarily found to be a bad thing. It is very much individualized, you know, case by case, different. And as you're saying, there's a wide range of differentials and I got to keep in mind all those differentials when I go see a patient. And always keep in mind drug, drug interaction. So I don't start antidepressants like, you know, right ahead from the scratch.

Yeah, so maybe we let's start with, when is this just adjustment disorder? So adjustment disorder, you know, they're just struggling with the adjustment to having cancer. It's not actually, like there's not the sort of the neurovegetative symptoms of depression. Yeah, any, what did you find when you looked at this, Shana? Yeah, well, I think kind of to add to that, when someone receives a new diagnosis, something like cancer, having a distress response is almost like a healthy response. So it is said to be the most common psychiatric diagnosis in patients with cancer adjustment disorder. And for adjustment disorder, kind of like how we treat adjustment disorder in other patients, psychotherapy tends to be first

line and there's less evidence for using medications to help patients with adjustment disorder. Yeah, I would agree. Like I think it's really normal to have. have a difficult time with that new diagnosis, you know, sort of struggle. Exactly. Yeah. Yeah. Do you, I mean, I'm sure you see that pretty ubiquitously. Usually the consoles that you see, you know, they're like simple word depression, but

you go there and you see the patient and you give him every right to feel fat right now or her. And it's really, yeah, sometimes you don't, what I, what I do, a lot of times it's just validation and acknowledgement of the symptom. And then trying to drag out the important features of, you know, where I really see it as a major depression. And even adjustment disorder is where you are adjusting poorly, where it's impacting all your life,

it's impacting your personal life, it's impacting your function. So even that is sometimes a heavy word for the person who's going through normal grief process or, you know, can still be happy. if it's distracted about the... Yeah, when do you tend to think this is not just an adjustment disorder, this might be more depression? If I want to go by textbook criteria, I might miss still some...

I might overdiagnose or underdiagnosed sometimes. So to me, again, if I want to just use my clinical judgment, and Hedonia is a very important is a very important feature for me. If the person is not able to enjoy anything, even out of context of being in the hospital in that setting. I ask the patient sometimes, if you were not diagnosed with cancer, if this stressor was not here,

do you see yourself being able to enjoy life? I mean, depending on what the answer is, sometimes they're like, no, I just don't, you know? So hopelessness and adonia, And really going along with the other symptoms that we have in depression, that helps a lot. Yeah. So when you see patients, like when are you alerted to this might, this might be something that you need to refer or, you know, like, is there certain symptoms that kind of like jump out at you? So actually, I wanted to step in, but I decided to wait a little bit.

I really do appreciate the job that you guys are doing and dealing with the cancer patient. I mean, my main difference in some certain point with my other colleagues is when I see, we see a lot of patients with the cancer. So cancer is becoming something not unusual to us compared with the other people. But when we see the patients and I see my other colleagues or the people who are, working in our team, they're saying that, oh, you know what, that patient has a cancer, and I think it's a little bit depressed, so I asserted this or that. So majority of the time, I'm the one that I disagree with them, and I say, hey, we need to

seek attention from the psychiatrists to talk to the patient, because we don't know, as you said, whether this is the adjustment disorder, or this is the normal grief, or this is the real depression or not. To me, I cannot realize and distinguish between these things. But do you guys, I'm sure that with five minutes talking to the patient, you can. And the other side is the medication that usually we are using for this kind of patients, specifically, for example, for a stem cell transplant patient or the patient who are under the chemotherapy, they have huge side effects if we are using some kind of medication that we really don't know whether there is an indication for it in the setting of the psychiatry or not depression i'm seeing that um usually they are giving the patient

okay let's start hold hold on let's start ad event let's start this or that and then a couple of days we see that there is a change in the patient that we cannot realize what's going on until we go back and review all the medication and then I will stuck with, for example, most likely adivan, Haldol or Cerecol, what's going on? Why? What's the indication? And then we will call you guys. And most of the time, I mean, no, really, it's really helpful because after you guys come in,

talk to the patient and trying to adjust the medication and get rid of the medication that we don't know it's interacting with the other medication, immune suppressant, or the chemotherapy that we are giving to the patient, and now patient get back to the normal and on track. So that's the main thing. Yeah. Yeah, the thing that really jumps out at me, specifically when I get consoles, sometimes I cover CNL,

and then in my work here in the MEND program, so in MEND we take on cancer patients for like IOP partial levels. So these are more severely anodontic, you know, high anger, tearfulness, several hours a day. So pretty disregulated is the way I'm going to define it. You know, the first thing that I'm thinking about is I'm thinking, are any of the meds that are on board making this worse, right? And one of the big things that I think therapists don't think much about,

and I think primary care physicians probably don't think much about, is more of that hypoactive delirium. and how many of the meds can can sort of promote this hypoactive delirium. So in hypoactive delirium, you can have that sort of, they can look apathetic. They can have suicidal or passive suicidal thoughts. But it's really distinguished because of that poor concentration, poor cognition and sort of sedation, right,

where they're just not able to focus. it's not able to concentrate anymore, not able to read books, not able to watch TV, if that was like sort of their normal baseline, you know? Yeah. Normally they could watch a movie

all the way through. Now they can't, now they're just like, they can't even focus on that, right? Right. When you're talking to them, they can't have the ability to comprehend well.

Right. You have to repeat your question. You have to repeat your phrases multiple times. And then the history that you get from the nursing that this is the fluctuation, like this past 24 hours, this person is fluctuating,

sometimes more cooperative with care, sometimes more apathetic, sometimes less. Yeah. Do you see the hypoactive delirium? A lot. Yeah? I didn't actually, I knew about this diagnosis, but this is the thing that we are missing all the time.

And I will get calls from the nurses on different patients that they're saying that, hey, this patient is not his or her baseline is acting too much or was talking normally yesterday but now is not talking so most of the time they are saying that even the nurse is telling me that i think he or she is a little bit depressed so we need to start something on it yep yeah so this is these kind of things i mean they know that there is something wrong but because lack of the knowledge they can't find the real because they don't know, so they will use the depression to describe that. So I don't have enough knowledge to go to that.

So at this time, this is the time that I can text or call or consult Mona. Oh, man. Shana, what did you find out about when you looked at hypoactive delirium in this population? Yeah, so something that I think helps differentiate hypoactive delirium versus depression is that you would most often see hypoactive delirium in the palliative care setting in older patients rather than younger patients. Generally, it's due to hypoxia, metabolic disturbances, and hepatic encephalopathies, and it's also associated with the higher risk of mortality. And kind of like we've been discussing, a distinguishing feature that helps is that degree of

cognitive impairment and the waxing and waning of it. Yeah, so it has a higher risk of mortality. It's not going to respond to therapy or to SSRIs. And I think a clock draw is really helpful. If they can draw a clock, like put the circle around, put the numbers around the clock, like you would see it on a wall, put it till 10 to 11. If they can do that, they're probably not hypoactive delirium.

That is very useful, yes, the clock's drawing. Or count down from 21 by 3. by three's, say the days of the week backwards, stuff like that where you have to like focus, concentrate. I think those are the quickest ways of sort of delineating that this is more of a hypoactive delirium. Any other thoughts on that? No.

It's a really good learning session for me. And Dr. Puder, you mentioned something very nice about the drug interactions. I remember when I was, well, at Loma Linda in a clinic, we had a patient that she was complaining of attention problem. And it was also clinically, you know, present in her encounter. So she was on amytripthaline for pain, low doses. She was also on well-butrin. I know we're going to go on this in detail afterwards. This is a good one to bring up, though. But I think this is the time. And then so well-butrin, the dose of

well-biltrin was increased. And she then came back complaining of cognitive problems. Right. And that was when you taught me at that time. This is a 2D-6 inhibitor. And it's probably, raising the amounts of amytriptylene more than intended? Yeah, so you have the, amyptylene is commonly used for pain. So you'll have primary care physicians or different doctors throw on a little bit of amytriptylene at night, which helps us sleep sometimes, right? But it's highly anticholinergic. So, you know, just like Benadryl is anticholinergic, you have amytriptylene, very anticholinergic.

and the breakdown of amatripline always and the tricyclics go through 2d6 so if you have a 2d6 blocker like fluoxetine paxil you know prozac paxil paxil or wabutrin um you can have increased levels of the amatryptylene and therefore increased levels of that anticholinergic and that is my like it's just it's just the the easiest win when I see a patient coming on that. But I feel bad because, you know, I'm sure that this is going on a lot more than I can diagnose. And I feel bad for these patients who now are sort of sent into this hypoactive delirium.

I know what it's like, you know what it's like to take Benadry on night when you're sick, take some NyQuil, there's Benadryl in there. Like when you wake up, you're just kind of a little bit more lethargic. You're a little bit foggy. You're less emotionally reactive. It's harder to concentrate. So that's hypoactive delirium. And also steroids.

Yes. Steroids can cause hyboactylure. And when you inject people with the chemo agents, what do you give as well? Benadryl, right? It's commonly used. I think everywhere that pre-medication before chemotherapy,

we will give Benadryl and the steroid. So both in order to get less hypersensitivity and reaction and cover the possible side effect of the chemotherapy. and the steroid also. Yeah. Yeah. And then being in the hospital increases risk of delirium, hypoactive delirium. So just being in an ICU, being in a hospital, there's much higher rates.

You know, people coming in all night, waking you up, checking your vitals, new people all the time, you know, it's stressful. And then having, you know, a comorbid infection, which is very common if they're in the hospital, right? Yeah. So all of these things. In the cancer population, they direct effects of the brain tumor, whatever, if they have a brain tumor. If they have leptomenegial disease, these are all different risk factors.

I was just thinking, you know, about different medications other than steroids. And we always, it's great to be, you know, informed and mindful of what cancer medications people are taking, even though we're not. oncologists, but there are a lot of times just side effects of the chemotherapy regimen that they're taking. What kind of do you know, what kind of chemotherapy regimens do you usually give patients that you suspect delirium? If the patient has a delirium, we are not processed to give anything that have a C and a side effects. For example, if the patient has leptominangel disease, one of the chemotherapy that we might try is high dose metatrexate. So high dose metatratexate has a CNS penetration.

Sometimes we use only intratical metatrexate, which goes directly to the CNS and it goes to the brain. But unfortunately, there are lots of side effects comes with it that we cannot prevent the patient with any kind of premedicate patient with a state. terawid or with Benadryl. The common side effect for the metatrexate, either if we are using it as a high dose,

which has a systemic effect as well as CNS penetration, or giving the intratical metatrixate is subacute, acute, or chronic locoencephalopathy, and bringing a lot of damage to the brain from the moment that the brain is going to be exposed to this medication and for the rest of the patient's life as a sickle of it. So these are the things that this is only one aspect

of the treatment for the patient. We are treating the patient, but with the expense of giving a lot more side effect to the patient later on. Yeah. Yeah, you know, when you're trying to keep people alive, there's sometimes like a risk benefit that we go through and it's tough.

Yeah, I also think like a brain radiation. I've seen it's going to, you know, anytime there's, you know, a hit to the brain, you can get pushed. Your sensorium is going to get pushed. Yeah. So even if, even if you don't get into the hyperactive delirium, which is like that sort of agitation, pulling out their lines, throwing things, hallucinating, you know, visual hallucinations. You can have cognitive deficits out of it sometimes. Cognitive, yeah, even if you don't get to that hyperactive delirium, you may get into the hypoactive. And then so as a nuanced psychiatrist,

you're looking at the med list thinking, okay, how do I minimize any anticholenduric medications? Ativan is gonna make this worse 100%. Any benzodiazepine, laurazepam, you know, clonopin, clonazepam. And I'm glad that you're bringing this up because I think it's an ongoing discussion in every council service. Oh, really?

about the side effects of like delirogenic side effects of benzodiazepines, anticholinergics, and cancer population is it more difficult to minimize their use sometimes because they are being used as an adjunct for nausea or hypersensitivity syndrome, but still it is it is something that we still play a huge role in, you know, just educating and letting everybody know that this person is suffering from hyperactive delirium as much as possible to minimize use of the delirogenic medications. Yeah. And on my website, in my resource library,

I have a nice Excel sheet that goes through every medication, and if it's anticholinergic, and how anticholinergic or cognitive, I'll share that with you. You're going to like this. I really need that. I wanted to ask you to send it to me, so I'm going to send it to you.

Anything else on hyperactive or hypoactive delirium, it's so important, and I'm glad we touched on that. Let's talk about suicidality. So patients with cancer, you know, to hire two times greater risk of suicide. Is that what you found, Shana? Two times greater risk of suicide versus the general population. And again, in cancer patients, often a fleeting wish to die can be normal. But if someone has persistent suicidal ideation, plan, or intent, that's when it begins to get concerning.

Yeah. I'm glad that you mentioned that sometimes it is. So we often receive counsels for suicidal ideations. And when we go see the patient, it's not really suicidal ideation. I'm sure you had the experience. What do we call the term wish to hasten death, which is basically a term when you are as a reaction to suffering in the context of a life-threatening condition from which the patient has no way out other than just accelerate his death. And really it's because the amount of suffering. and they know that there are advanced cancer age. But this is not a wish to die, really. And if we can decrease the suffering, you will see the patient shifting from that wish to wanting to live longer, really. Yeah. Yeah. What questions do you ask specifically, Mona, to sort of delineate if this person is experiencing just the first,

fleeting sort of passive desire to be dead versus, you know, this is more of an issue, like this is a chronic ongoing thought process. I usually look at the circumstances like, okay, how much physical distress the patient is going through, but how much like everything factors around it. But my policies usually direct questions asking the patient directly if, like the exact thing that I'm thinking, right? I've just explained to you, I will just ask them,

do you think it is a reaction to your suffering? Do you think if you were not in such and such pain or like pruritis or burning or all these symptoms or respiratory distress, would you still want to die? You know, I would just ask them directly a lot of the times and also do a like more symptom history. Yeah.

And the family members are very helpful also in giving you, important collateral that helps you distinguish. And I actually had a question about suicidality and this population that came up during my palliative care rotation. This patient wasn't specifically a cancer patient, but he was an elderly male who his whole life had been very active, very independent, and he had a stroke. And following the stroke, he wasn't able to tend to his needs.

And to him, his independence was the most important thing. and he expressed to us that he wished to die and he just wished to be discharged home. And I guess my question was, like, in a patient like that who is expressing suicidality, like at what point do we put them on a hold versus we say, okay, we're going to respect your wishes? It is not one answer, you know, net answer easy. But I think that really you look at the context and if you diagnose clinical departments, that is a whole different story. So you cannot allow that patient to go with their wishes to die.

If it is like a suffering, a lot of like they're going through suffering and you just try to work with them to ease their suffering. I don't know. What is your input, Dr. Puter? I think it's, I think it's dangerous to almost have a blanket statement because people are so individual in the situations are so, you know, so different. Like if this person, you know, like let's say it's their. you know, third time that the cancer has come back and they've been in the hospital for three months

and, you know, they're like, you know, I think I'm ready for nature to take its course. I think I'm ready to just, you know, not have so many of these treatments that are keeping me alive and just to allow my life to come to an end. I really respect that. I really do. I don't know if you, you probably have these conversations more frequently than I do with the specific population? Yes, we do.

And it depends on the patient. If the patient is a cancer, there is a publication in New England Journal. I think it was 2017 or 18. And they showed that early involvement of the psychiatrist and palliative care from the time, the initial time that the cancer was diagnosed, no matter the stage, would have a huge impact on the patient quality of life and actually the overall survival of the patient, which before that, everyone was kind of thinking, okay, we will save palliative care and psychiatry for the last option and resort when we did everything for the patient, we threw all the treatment

and everything, and now we are desperate for the help and for the help and patient, is kind of very depressed because of not having access to the treatment. And actually, I was starting doing it during my fellowship and my thought before that was it's inappropriate, but when I was talking to the patient and giving them this information and then follow them through this, I saw that how much they are really happy throughout the treatment.

However, in the patients who are coming after receiving a lot of treatment and now, for example, wants to go for a stem cell transplant. One of the major criteria before going through a stem cell transplant is getting the clearance by the psychiatrist. So every patient should go as a part of the pre-planned check, see different kind of doctors, but one of the most important one is a psychiatrist. Mental health clearance. And mental health clearance.

Not necessarily psychiatrist, right? Because, yes. Because we have to make sure that after the transplant, will able to cope with this new life and specifically following the instruction about what to how to get the information correctly from the different person, how to follow me as the transplant physician, taking a lot of medication, making sure to come to all the appointment, not missing any appointment, not going to the birthday, not going to the trip for a while for for one or two years and all these things.

I mean, it's not easy, but having such people like you guys, palliative care, supportive care, psychologists, psychiatrists on board will make our life and patients life a lot more easy. Yeah. Well, I hope so. I hope it makes their life better because that's what we're trying to do. You know, we want to make people's life just a little bit better in the midst of the struggles that they're going through.

Okay, so anxiety, another big category of symptoms. 10 to 30% of cancer patients have significant anxiety. Shauna, what did you find out about sort of the prevalence or the commonalities? So most patients who endorsed having significant anxiety actually have an underlying problem with anxiety already, and then with everything that's going on on top of it. that tends to get exacerbated. And in patients who have undergone treatment, they may be in remission, those anxiety symptoms can still persist and remain for them for a long time.

When addressing anxiety, the most difficult thing is really fighting that underlying cause for anxiety because a lot of medications can cause anxiety, medical conditions, anything that causes difficulty breathing can also cause anxiety because patients are going to feel breathless and that chest tightness. Yeah, specifically, I mean, think about how calming different breathing practices are, like yoga breathing or, you know, four seconds in, hold it for four seconds, four seconds out, hold it for four seconds, four seconds in, you know. So it's like that kind of square, four second breathing is calming.

So it kind of brings us into that more parasympathetic place, that rest and relaxation place. And think about like how many diseases cause you to have short, fast, breathing, you know, so naturally you're moving out of that nice, you know, parasympathetic sort of nucleus sort of directionality. You know, you're moving out of that parasympathetic into more of that sympathetic system just by having a disease that's causing you to have short breaths. I could go on about that. I think it's interesting how I've talked to people who put people on vents. And there's one doctor specifically who has found that certain breathing patterns on vents makes the kids more relaxed so that they can laugh more. And so thinking about how breathing relates

to anxiety. Okay, go on. In terms of treatment for anxiety, we kind of talked about how benzos are pretty tricky to prescribe, especially in this population. But benzos have been used preferably short-term and SSRIs, SNRIs are better for long-term treatment. But psychotherapy actually has the best evidence for treatment of anxiety. So things like supportive therapy, educational therapy, and even complementary approaches like acupuncture, massage therapy, creative art therapy, those can also be really helpful in patients with anxiety. I was going to say that sometimes you see this anxiety.

I mean, you see it a lot in cancer patient as a normal reaction. to this whole diagnosis, treatment, because of the uncertainty of what's going on, because of the fear of loss of control, the fear of dependence on their loved ones, future dependence. And a lot of the time, this anxiety peaks at the crisis points where you either have the diagnosis,

you either want to start treatment, you have a recurrence in diagnosis, you want to go to infusion for your therapy. And sometimes, it is as an anticipatory anxiety where because of the difficulty of the experience you went through, then before even you start the treatment, before even going to your doctor appointment, you start with feelings of anxiety. And it is very common in cancer patients.

And then when I was talking about impact on family members, anxiety is one great example where presence of anxiety in one, in one, um, partner increases the chance of anxiety and the other partner. So if the, let's say the cancer patient is dealing with his diagnosis, but if the partner has anxiety and is not being addressed properly, that can add to the patient's anxiety. So as a symptom, this is important to look at. There is this fear of cancer recurrence in anxiety where this is just also in studies it's been shown that it's more common in the caregivers of patients with cancer at sometimes,

and 70% of patients go through that, even more so after they're treated, after they're in remission, they still remain with this fear of cancer recurrence that can be, you know, can be misdiagnosed with an anxiety disorder, but it's just a part of their journey going through it. One thing that I think about is what medications are they on that might be worsening the anxiety. So I immediately think, you know, the steroids, a big culprit. So I look at the timing of when the steroids was given and when the onset of the anxiety was, right? So getting that history of when the anxiety started, when what medications started, you know, thinking through. Yeah.

Is it this, because steroids can cause, you know, hypomania, mania, psychosis, depression, anxiety can cause delirium. It can't cause any psychiatric issue, right? Right. And then the second thing is, you know, are they on some sort of dopamine blocker, like anti-aimetic? Which they are always. A lot of the times, prochlor, parazine or thorazine.

Yep. So that's a nice anti-emetic, but it's a dopamine. And so with dopamine blockers, you can get acesthesia, which is an inner restlessness needing to walk around external restlessness. So inside they just feel this need to move all the time. And I think that that is a solid win when we catch that, you know? I think of you every time I hear acosthesia. Why?

Because you had it, did you have a podcast episode dedicated to acesia? Not something like, I talk about it enough. about it enough. It's just very common. In every, in every episode on schizophrenia, I talk about suicidality with. Suicidality, acesthesia. Yeah, it's a very horrible feeling. And whenever I post on it in social media, there's someone who puts up a comment like, oh, I've had that and that was like the worst week of my life. Yes, this inner feeling of restlessness where you're not necessarily worrying about anything. Yeah. It's like a bodily, a bodily, a bodily, restlessness, yeah. And, you know, it's one of those things that we can catch and then we can

treat. We can take them off the dopamine medication. Metaclypropramide can cause that as an anti-emetic also with dopamine blockage. Yeah, that's good. Yeah, it's good that you, we already discussed like the respiration, how it can affect anxiety, hypoxia, it can be a symptom of pulmonary to emboli, this other medical comorbidities. So it's not always a primarily anxiety problem in the patient. But I wanted to talk about pain too. Pain can cause anxiety, but the interesting thing that I read recently was found was that anxiety and depression have more huge burden on pain than pain has on them.

So anxiety can really amplify pain and untreated anxiety. Yeah, I was thinking about that. we didn't mention pain with hypoactive delirium, but opiates, right, can worsen delirium, but then untreated pain can worsen delirium. Yes. So it's like, what are you going to have? Finding the middle path between this.

You have less pain, right. And then anxiety, you know, opiates can decrease attachment pain as well. So it's like, you know, are they worried about leaving their loved ones? and that's part of the anxiety. So maybe if they get that treatment for their pain, their physical pain that comes to cancer, maybe it helps with that sort of psychic pain as well. The problem is when they're on chronic opiates

and then they get like a hypersensitivity to depression or, you know, sometimes it can make depression worse or anxiety worse long term or you can just make them less functional. Or like a lot of chronic opiate users are just like in bed often because they're just not, you know, needing to seek out connection with others or, you know. Yes. Any substance like that the patient is now deprived of while they're inpatient. We got to keep in mind like marijuana, nicotine, they're not having access to that anymore here.

So how is that anxiety partly? Is it related to that poor access to some sense as part of the withdrawals of whatever they were using? if they're coming out of surgery where they were hugely sedated with medizolum, like strong benzodiazepines, propophol, and now they're coming out of this, they're either delirium or not, but this anxiety can really drive from

some withdrawals of the sedative medications, especially in older ages where you have slower metabolism, and as you go along, you see this anxiety kind of fading away more slowly than a young person who comes out of surgery. That's good. Yeah, and because benzos are the treatment of aceshesia, I've had one patient who was on risperdol who getting them off of the clonopin unmasked the aceshesia underneath. So it wasn't even the withdrawal from the clonopin. It was actually just not having the clonopin that was treating the aceshesia. So it can get, there can be some like nuance there. And so getting the full medication history when the medications are started, when the anxiety was started, you know, and thinking, especially as a psychiatrist,

what are all the different things that might be leading to this heightened level of anxiety? Okay, shall we get into effect sizes? Okay, so we're going to go through some of the different treatments, and then the last portion we're going to get into some of the nuance of the P450 system. So let's talk about effect size. Yeah, so effect size is the difference between the treatment and control group expressed in standard deviations.

So, for example, if an effect size is one, it means that the treatment arm moved one standard deviation away from the control group. When looking at effect sizes, 0.8 is considered a large effect size. 0.5 is moderate and 0.2 is small. Yeah. And so the point of this is for us as clinicians to decide if this treatment is worthy to continue to prescribe based on how strongly it's going to make an impact in someone's life, right? So let's talk about this meta-analysis on exercise. What do they find? So this is a meta-analysis of almost 5,000 cancer patients,

and it was looking at the impact of exercise on cancer-related fatigue. And these authors found that exercise had a mean effect size of 0.32 on reduction of cancer-related fatigue during cancer treatment, and that effect size increased to 0.38 following cancer treatment. Yeah, so how much exercise is recommended by American College of Sports Medicine? 150 minutes of moderate intensity exercise per week, actually. How would that would be, I was thinking, two to three hours a week. That's a lot.

That's a lot. How many of your patients exercise? Is that a lot? It could be hard for a normal person, let alone someone who's struggling with cancer. I do know because I'm in this sort of strength community that there are some people who continue to lift weights, squat, deadlift in the midst of going through chemo, going through radiation.

And there's a couple of these case studies that are well known in our community of people who have had like, you know, cancer and continued to get stronger in the midst of it or just maintain and how valuable they found that for themselves in the midst of it. You know, like if I'm not losing weight, I'm not dying.

type of attitude. That's correct. I mean, I was amazed and almost every day when I see patients in the clinic, some of them I truly am learning about the way that they are looking into the life after the cancer. Let me give you an example. I had a patient that it was like a two or 63 years old, very good guy. very nice guy with the transplant and initially we had a problem with obesity. So overweight, but when I see the patient in the clinic, I said, hey, I can't imagine if you

lost like 200 pounds in one year and a half after you got the transplant and what are you doing? He said that, you know what, I'm biking. I said, you're biking where you cannot bike, you know that. because outside you cannot go outside and do the biking. I said, you know what? I found my way. And I said, okay, I'm interested to see what you're doing. And he told me that he designated a kind of room in his house.

And he put a bike there. There is a huge camera back on the bike on the ground. And there is a screen on the wall. and he said that, you know, there is a program that you can buy for it and it's a virtual biking and you can do it like you are in the middle of the game or biking racing with other people like in Paris, like in London. And you can do it like for two or three hours a day as long as you can. Wow.

And you see, this is the way that I see, wow, people can find a way even if they are dealing with the cancer or the side effect of the cancer no matter what. I mean, I think it depends on the person and the way that they are looking to the life. Sometimes with the cancer, they are looking in the life that, okay, my life is over, that's it, I will fight, but not for more than that,

but another people will look at it as a new opportunity that the life gave it to them, no matter what would be the end point. So this is kind of difference that I realize that the patient, I can divide my patient between these two. Yeah. One more thing about cancer-related fatigue. Medications have been considered like psychostimulants, such as methamphetamine, modafone, medaphanol has also been used.

But looking at studies that compare the effect sizes of treatment with pharmacotherapy with these psychostimulants versus exercise, we actually see that exercise is a lot more effective than these medications. And even psychotherapy is better than medications for treating cancer-related fatigue. Yeah, let's go into psychotherapy a little bit. Like what have we found the effect sizes for psychotherapy on like anxiety, depression, stuff like that? Can I talk about fatigue a little? Yeah.

About 40% of cancer survivors struggle with fatigue. That's a huge number. And then 100% of those cancer patients going through active treatment struggled with fatigue. I had a patient yesterday telling me, she said, I've always been very active. I've always heard of the term fatigue, but I never understood what it felt like really when I experienced it.

And she said it's hugely disturbing. No matter how much you rest, it's not going to help. And it's really in proportionate to the level of exercise, to the level of activity. So this is disturbing and I'm glad you brought it up. Yeah. And I would also, for fatigue, put in the differential there, hypoactive delirium. Again. Because you can get that with fatigue.

And also look at the medications that could be making someone feel tired. Okay, let's talk about psychotherapy a little bit. So what did you find in the studies on psychotherapy? In studies looking at CBT for the treatment of depression and anxiety and cancer patients, it has shown to be effective. But some of these trials haven't pre-screened patients, so they're looking at patients that haven't necessarily already been diagnosed with anxiety or depression. So that could be problematic.

and it's also very much for newly diagnosed cancer. It can help the person how they look at that diagnosis, how they look at the start of treatment and the change that it's going to impact on their life, put on their life. Yeah. I think there are very highly beneficial, newly arised psychotherapeutic methods specific for cancer patients that can be applied actually to any. one in medical comorbidities too, but more for advanced cancers.

Yeah. You have... Yeah. We have, in our program here, our effect size is about two for physical issues, so for pain, and for about two for the psychological issues. And, you know, but this is like psychopharmacological treatment, you know, optimizing their sensorium, psychotherapy, you know, 30 sessions. three hours each session.

So it's quite a big dose, but we're getting a really good effect size. And I think for the, for most studies, 0.6 to 1 is what you're around what you're going to get in like individual weekly therapy. It'll go up if it's longer term therapy. Also think about, I think with cancer patients,

like what are their sources of strength that they've utilized throughout their life? So if like spirituality is an important thing for them, how do they reconnect with that or connect with their, you know, spiritual mentors if they have one. So kind of like thinking about how they can existentially approach their struggles within their own sources of strength as well. I think it's really important. Can we talk about ACT? Yeah, sure. So for the acceptance and commitment therapy, go ahead. So ACT is a CBT variant that aims to change the function of distressing thoughts at the individual level and teach patients to reduce

the influence of these thoughts on their behaviors. And there is actually a really interesting study that looked at ACT versus what the authors called treatment as usual, which just comprised of commonly used cognitive and behavioral components. And this study actually found pretty impressive effect sizes for ACT versus treatment as usual. For the improvement of distress, the size was 0.89. For anxiety, it was 1.25. For depression, 1.69. And for overall quality of life, the effect size was 1.35. Yeah, that's nice.

That's good. So the other modalities that I was talking about, like dignity conserving psychotherapy for advanced cancer, meaning-centered psychotherapy, and then life narrative, psychotherapy, existential. A lot of these help with advanced cancers and a lot of the times with demoralization,

which is also one of these diagnoses that can be misdiagnosed with depression, this sense of hopelessness, a motivation, and mostly in if the person is single, jobless, you know, again, advanced cancer and later stages of their lives. Right.

Purpose meaning. To give them tools to be able to find a purpose and meaning. and come up with the legacy of their life. Yeah, Victor Frankl's work on Logo Therapy and looking at how people found meaning in the midst of horrible things, like the concentration camps, you know? You know, cancer is kind of like one of those like life events

that I've seen people come out and find even more meaning or more thriving in life. Not that that always happens or always needs to happen, but sometimes it does, and it's like, oh, wow, what led to that transformation? You know, I get curious about that. Do you see this ever with some of your patients where they just, there's like, they almost start living more?

I do see, but it's like a spectrum. It depends on the patient. I mean, fortunately or unfortunately, I don't know which one is the correct word here. There is not one factor involved in this kind of patient, whether they truly find a meaning and purpose at the middle of the crisis in their life. But I do see, and it's really amazing for me. And to be honest, sometimes I will consider myself and I put myself in their shoes and see what would be my

reaction, what would be my thought. And I can't come to any conclusion to myself that, whether I would come to this point that this patient now is looking at life differently in a purposeful way or not. I had a couple of the times I was thinking about this and I was talking with the mona about it. And this is difficult. This is difficult. And the goal is finding a purposeful tool and the way that you look into the way that you look into life after having a cancer. But I don't know what would be, for example, my reaction if it comes to me.

And I don't think there is any wrong or right answer to this. Yeah. Yeah. I think dignity therapy is so cool. The idea of dignity therapy is that you allow your patient to share details that capture their essence and to say, things that they wish to say. So you ask patients a set of questions where you explore things like, like, when did you feel most alive? Or what are your hopes and dreams for your loved ones?

And after this interview, you compile all these responses into a kind of beautiful narrative. And that helps the patient preserve their sense of meaning, purpose, and worth. And it also serves is something that can be really therapeutic for the family once the patient passes. Thanks for sharing. That's very important. That's really good. Okay. Next we'll look at the effect size for pharmacotherapy.

And I think what's really important to notice here is the effect sizes are going to be smaller than psychotherapy and exercise because we're comparing it against a placebo, which placebos themselves have a powerful effect. on people. And so, you know, there is no placebo for exercise or for, for therapy. So although the effects sizes are smaller, that doesn't, it's because you're basically comparing it to something that also works, right? Okay. So go through some of the effect sizes. So looking at pharmacological trials, effect sizes range from 0.26 to 0.61. Deciproamine, for example, was found to have an effect size of 0.26, and paroxetine was found to have an effect size of 0.47.

And then looking at psychosocial interventions such as education, relaxation training, these have an effect size of 0.46 to 0.74. Yeah, an interesting modafinol for fatigue was pretty low. The effect size was like 0.1 or 0.7.4. 0.09. Yeah, so I think it's really important to note that these are compared to placebo. So I think as someone who's, you know, looking at studies, there's a little bit more nuanced to that and that discussion because plasebos are powerful. Plessibas are powerful, yeah. Let's talk about choice of medications. We have about five more minutes. So we're going to,

we have, I don't know, 40 pages of notes on medication. So there's a lot of new here. Maybe we'll have to do a part two, but in the meantime, we will give you these notes in the resource library for you to look over because there's a lot of nuance specifically with like the P450 interactions, so how medications are broken down. But let's try to go through some of the pearls in the last couple minutes. Yeah. So let's talk about tamoxifen. So tamoxifen used for the treatment of breast cancer is an estrogen receptor blocker that decreases levels of estrogen and that's thought to... Yeah, yes, so estrogen receptor I always like to...

I remember this from medical school and I don't know why I hold on to it. It's estrogen receptor blocker in breast cells, but it's estrogen receptor agonist in hypothalamus. So, but in breast cell, it actually prevents growth of breast cancer and cells. that's cool and given yeah and so you we want this tamoxifen to be metabolized by 2d6 into the active form and so if we're treating someone with a 2d6 blocker they may not be able to get the active form of tamoxifen endoxifen is the active form yeah endoxifen so an endoxifen has like a hundred times higher affinity for the estrogen receptor than the parent compound than when it starts out.

So I've had patients who are put on this and then they come see me. And this one specific patient was on fluoxetine, Prozac, which is a 2D6 blocker. And so I had to change them, which was sad because they were doing so well on this one. They did well on the second one, but we don't want to change things that are doing well in general. So we had to change it to something else, right? And the other situation is if they're on like paroxetine, paxil, which is a heavy 2D6 blocker, we're going to have to change it to something else.

Yeah. What do you think? Well, as I said in the beginning, it's a learning session to me. So I feel very lucky to be here. And now I know a lot of things that most of my colleagues I don't know. Yes, that's true. Actually, tamoxifen is a really, really good medication. And these days we are using it extensively as a hormonal therapy for the patient who they are,

we call it ER, PR, or estrogen, or progesterone receptor positive cancers. Because as you mentioned, the mechanism is, they are going and blocking the estrogen receptors that the breast cancer cells, they love those receptors and they will go find them. Wherever there is a sturgeon, they will go find them. And that kind of is feeding the cancer cells. So when we are using the tamoxifen, we are blocking that kind of feeding and the food court for the cancer cells.

And it's really, really important, the type of the medication that, that we might use sometimes to help people, for example, for the depression or going see another doctor and save them an appointment and waiting line. But at the end of the day, our purpose of giving that specific medication like flaxatin is good, but it's not good for the patient down the road. And it's really good to know this kind of information

and I will try to share this information with my colleagues. So it would be better than nothing, but... Good. Good, yeah. There's actually this really cool study looking specifically at SSRI use in breast cancer patients taking tamoxifen. And the study actually found that patients taking strong SIP-2D6 inhibitors, such as peroxitine, had increased mortality compared to patients taking weak inhibitors, such as Vemoisin. Because they had reduced efficacy.

of their toxin. Yeah. So this is a good, this is a good pearl. So what are the, so it's good to go over like, they're strong, level of strength in 2D6,

SIP2D6 inhibition in terms of SSRI, SNRIs. It sounded like Paxil or peroxitine and Prozac are one of the strongest. Zoloft and symbol of, Zimbalta can be in high doses and have 2D6 inhibition. So in lower doses, Zoloft under 200 milligram doesn't have significant 2D6 inhibition.

But one of the very lowest ones are EFexor. And then myrtazepine is not in that category, but it has very low 2D6 inhibition properties. So we tend to go more with those. And then Lexopro, Selexa are in the, And in between, you know, after X, Affector, if you couldn't use that, Lexa ProSlexa would be your next option. Yeah. And I think there's other reasons to use Afexer-Venlo-Faxing.

Or hot flashes, tamoxyphine can cause anxiety, hot flashes, and as a side effect, potentially, where SNRI, such as a FXER, can play a role there. Yeah, and Shana was sharing me from her reading that she found that hot flashes are a good thing. Oh, yeah. So hot flashes can possibly indicate a better prognosis because when less estrogen is present, women tend to have hot flashes. So having a hot flash might be an indication that the tamoxifen is working. It's working. It's good to share with patients when they're suffering from it. And then how we can manage that. And then we try to treat that with the effects or the desophant the vaccine. And the death of the vaccine, actually, there were some good studies that show that that could be helpful because you don't, even if you're on a 2D6 blocker, you still get the active form of the, because FXer turns into death of vanilla vaccine. So desolate vaccine is a medication we can give, which is the, uh, the active form. Yep. And it doesn't go through the 2D6.

So you, um, you can, uh, still get the active form if you have a 2D6 blocker from one of the other meds that they might be on. Very good. I think we're going to have to bring this to a close today. This is like amazing. Man, we could like, we could totally do a whole series. We could talk for hours. I think bottom line for medication, as you said, prior response to treatment is so important. We still want to keep that element in mind.

And like the medical comorbidities, drug-direct interactions, I just want to kind of wrap up that in pharmacotherapy of cancer patients with psychiatric for comorbidities, root of administrations, a lot of time you have a patient where you just cannot take any oral or sublingual because they haven't passed their swallow evals. So you need to think about medications that you can give IV and also length of, you know,

onset of action of the medication, like given the time that the patient has left, where do you, you might start thinking about psychostimulants as the mode for increased energy. less for depression, but more for energy and more active lifestyle. Yeah. Because of the rapid onset.

Yeah. And so I'll have Mona take a look at these notes, co-author them with myself. Thank you. And we'll put these up and maybe we'll come on for part two if I get some comments that you guys would like to hear more. Great. Thank you very much.

Thanks for having us. Yeah. Thanks for having us. Thank you for coming. It was awesome. I think people who are treating this population are really going to appreciate this. And I'm sure also some like patient who's struggling with depression or anxiety,

you know, who has cancer is going to listen to this as well and hopefully find some value. Great. Thank you so much. Thank you.