Chemobrain, Steroid Rage and Other Ways Transplant Meds Affect Your Brain

Chemotherapy, steroids and some of the anti-infective medications that patients receive during a stem cell transplant can affect how the brain functions. Learn which drugs cause problems and what to do about it.

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Chemobrain, Steroid Rage and Other Ways Transplant Meds Affect Your Brain

Monday, May 1, 2023

Presenter: Adrienne Mishkin MD, MPH, MS, NewYork Presbyterian/Columbia University Irving Medical Center

Presentation is 20 minutes long followed by 34 minutes of Q & A.

Summary: Chemobrain and steroid rage are common side effects of drugs used during a stem cell transplant. This presentation reviews the causes and symptoms of these problems as well as the prospects for full recovery from them.


  • Chemobrain can be caused by any type of chemotherapy. It can start weeks or months after chemotherapy. It does not usually get worse and can improve with time.
  • There are a lot of psychiatric side effects of steroids used to treat graft-versus-host disease (GVHD). The most common ones are feeling anxious, agitated, irritable or moody. About a third of patients on steroids will have mild to moderate psychiatric effects.
  • Knowing what to expect can be helpful for people at risk for chemobrain and steroid side effects. Family caregivers can help by reporting symptoms of these issues to the patient’s healthcare team.

Key Points:

(02:14): Patients with chemobrain often report feeling “delayed” and not as focused as they used to be. It can take longer to think of what they want to say and they may have short-term memory problems.

(02:39): Chemobrain is less severe than dementia.

(04:17): Chemotherapy can damage neurons in the brain, which can affect the speed with which one can do certain tasks, and the hippocampus, where memory is stored.

(06:50): Chemobrain can be treated with cognitive retraining therapy.

(10:09): When steroids are stopped or significantly reduced, most people feel low, tired and/or sleepy. Some will still have anxiety, mania, or confusion.

(10:35):  About 40% of patients who are treated with steroids will have some kind of psychiatric side effect in the first week after taking steroids. Almost two-thirds will have symptoms within two weeks, and most within six weeks.

(11:31): The psychiatric side effects of steroids can last up to two months after the last dose of steroids.

(11:57): Steroids can cause exaggerated emotions and trouble sleeping.

(13:06): Steroid side effects may be lessened by changing the dose or switching to other medications.

(14:55): Several antibiotics, antivirals and antifungals can cause psychiatric side effects, especially Voriconazole (Vfend®)

Transcript of Presentation:

(00:01): [Steve Bauer]: Introduction. Hello, and welcome to the workshop, Chemobrain, Steroid Rage and Other Ways Transplant Meds Affect Your Brain. My name is Steve Bauer and I will be your moderator for this workshop.

(00:13): It's my pleasure to introduce today's speaker, Dr. Adrienne Mishkin. Dr. Mishkin is assistant professor and psychiatric liaison to the Blood and Marrow Transplantation and Cellular Therapies Program at NewYork Presbyterian/Columbia University Irving Medical Center. Her interests include psychiatric care of patients with life-threatening illness, cancer, sickle cell disease, infertility and sub-fertility, medical post-traumatic stress, clinician mental health, surrogate decision-making, public health, access to care, and equity. Please join me in welcoming Dr. Mishkin.

(01:06): [Dr. Adrienne Mishkin]: Overview of Talk.  Hello. My name is Adrienne Mishkin and I am a psychiatrist. I work with the stem cell transplant and cellular therapies program at Columbia University Medical Center at NewYork Presbyterian Hospital in New York City. Today I'm going to talk with you about some of the medical treatments that are part of transplantation that may have an impact on your brain, mood, or other psychiatric symptoms. We're going to focus on chemobrain and steroid rage, but we are going to cover some of the other medications that commonly cause psychiatric side effects as well.

(01:47): The learning objectives of this talk are that participants will know about chemobrain, what causes it, and how it looks. They'll also learn about steroid rage, its causes, treatments, and how to handle it. And they'll learn a little bit about some of the other common medications in transplant that impact the brain, mood, and cognition.

(02:14): Chemobrain has several symptoms including delayed speech, thinking and memory. So, what is chemobrain? Patients who take chemotherapy often report feeling that they are not as focused as they used to be. It takes longer to think of what they want to say. They may experience short-term memory problems. In general, the theme tends to be that they feel delayed.

(02:39): Chemobrain is less severe than actual dementia. So, this is important in contrasting with dementia. In dementia, patients often experience severe memory changes, personality changes, and even outright confusion. We do not expect those symptoms to come from chemotherapy. It's usually described that the patient will feel it takes them longer to come to the same conclusion, longer to come up with the same word, phrase, or idea, longer to get their thoughts across, but not that they ultimately say something that isn't consistent with their previous personality and way of thinking.

(03:17): And I think that's really important because things that change your brain can feel pretty scary, so it's important to know that we would not expect you to be not yourself. If you are not yourself, we would expect that to be due to some other acute medical cause and not chemotherapy.

(03:37): Chemobrain can start weeks or months after chemotherapy but it does not usually get worse and can improve with time. The symptoms of chemobrain can start weeks or even months after taking chemotherapy. But once it happens, it does not continue to get worse over time. And some people actually improve even years into their recovery.

(03:54): The medical term for chemobrain is chemotherapy related cognitive impairment. So, is chemobrain real? Well, yes, everything you experience is real. But most people ask this question meaning: Is it medically something that we can explain? And yes, we can. The medical term is chemotherapy related cognitive impairment, and there are specific biological explanations for this phenomenon.

(04:17): Chemotherapy can damage neurons in the brain, which can affect the speed with which one can do certain tasks, and the hippocampus, where memory is stored. The neurons, themselves, are being damaged by chemotherapy. Neurons can be long and spindly or they can be tight and thick. The neurons that happen to be flimsier are more likely to be injured and impaired by chemotherapy, which is why people have certain specific things that work slower and other parts of their brain that seem to be working fine.

(04:43): The hippocampus is the part of the brain where memory is stored, and the cells in the hippocampus tend to be affected by chemotherapy. Then there are the other cells in the brain that can be inflamed, and that can also contribute to the experience of chemobrain.

(05:02): So I'm going to show you an image of fMRI, which is a type of MRI that is done when the patient or subject is doing a task, and they're looking at how much blood flow is going to different parts of the brain while the patient does the task. So, in this image, patients A and B were actually identical twins doing a memory task. And you can see that there's more blood flow in the A brains and less blood flow in the B brains, which is a way of measuring how much activity is going on in the brain. The more activity there is, the more blood you need.

(05:42): And you can see that in the first two images, the A brain has much more activity than the B brain. But in the other images, there's less of a difference, and that goes hand in hand with what I mentioned, that certain parts of the brain and brain function are more affected than others.

(06:04): Chemobrain can be caused by any type of chemotherapy. So what causes chemobrain? It can be any type of chemotherapy. Methotrexate is a commonly known cause and a common medication used for transplant patients. Any chemotherapy that you have injected into your spine might be more likely to contribute. Of course, the purpose of injecting chemotherapy into the spine is to make sure that the chemotherapy reaches the brain and protects the brain from any cancer. So of course, chemotherapy is more likely to get to the brain. And not while not chemotherapy, radiation that includes the brain also contributes to cognitive changes and it's a very common treatment that's given along with chemotherapy, so I've included it here in the chemobrain section.

(06:50): Chemobrain can be treated with cognitive retraining therapy. So, what about treating chemobrain? Can we do anything about this? There actually is a type of therapy called cognitive retraining therapy. It is specific mental exercise that can help sharpen you. It's also possible to find ways to rely on those things your brain does best. Everybody can do this to some extent. You don't have to have cognitive impairment to want to do this.

(07:17): I'm a person who has an easier time with languages and words and a harder time with math and numbers, and so I always translate things into a way of thinking about them in words. I rely more on the part of my brain that works better, and I rely less on the part of my brain that works worse. And there are more complex ways to do this with the support of a trained clinician.

(07:40): This type of therapy can be done with a psychologist, psychiatrist, physical therapist, an occupational therapist, or as part of an integrated center for cognitive retraining therapy. And there are ongoing studies of what the best methods are.

(07:56): The medication, Namenda®, which has also been used for dementia, has been studied for protection against chemobrain. There are some signs that this may work, but it's a little bit too early to really say for sure. And there's one study where it was shown to protect brains from the cognitive effects of radiation.

(08:12): Thiamine, which is just a vitamin, is also being studied for protection against chemobrain. Thiamine is a vitamin. Very often, when people have a deficit of thiamine, it can correlate with problems with the brain, nervous system, and spinal cord. So, this is, potentially, a hopeful thing that could be added that pretty much has no downside.

(08:34): Now we're going to talk about steroids, which are the other very common part of a transplant that uses donor cells. Everybody is getting treatment for immune suppression, and a lot of patients wind up having treatment for graft-versus-host disease (GVHD) or other similar conditions. Steroids are widely used in the transplant arena.

(08:56): There are a lot of psychiatric side effects of steroids. The most common ones are feeling anxious, feeling sort of agitated, irritable, an elevated mood, but in a cranky way. It varies tremendously, but in general, the most common experience patients have is that they feel that their emotions are being amplified in one way or the other. It could be amplified sadness if you're feeling sad.

(09:29): About a third of patients on steroids will have mild to moderate psychiatric effects. Then there are some less common symptoms that we really need to be on the lookout for like actual psychosis, meaning seeing things that are not there, hearing things that are not there, having beliefs that are strange and magical, or not being able to get yourself together to focus on what you're doing. Of the people who have been on steroids, almost one in three will have a mild to moderate psychiatric side effect, so it's very common. Only 6% will have a severe psychiatric side effect, but of course we need to know about those and how to handle them.

(10:09): When steroids are stopped or significantly reduced, most people who felt sort of amped up on the steroids feel the opposite when the steroids are finished. They feel low, tired, sleepy. Some people can still have anxiety, mania, confusion, but most people feel depleted, like my little cartoon man there.

(10:35): Psychiatric side effects from steroids may take several weeks to occur. So, when after taking steroids are you expected to have these side effects? This is the tricky part. It could really be any time. About 40% of patients will have some kind of psychiatric side effect in the first week after taking steroids, but plenty will have their first symptoms later. Almost 2/3 will have those symptoms within two weeks, and most within six weeks. It's very common that the first psychiatric side effects do not occur during the first few days, and so later, when they occur, everyone thinks, "How could this be from the steroids? You've been on them for a week already." The average number of days before psychiatric side effects begin is 11. So, it's important not to discount the role of steroids in causing these symptoms, especially if there's no other obvious explanation.

(11:31): The psychiatric side effects of steroids can last up to two months after the last dose of steroids. This is probably something people starting steroids don't want to even think about, that they could have psychiatric side effects the whole time and then even after they're stopped. But it's so important to know that even if it's been a few weeks since your last dose of prednisone, these symptoms are still very likely to resolve over the next few weeks.

(11:57): Steroids can cause exaggerated emotions and trouble sleeping. So, what do you do? Expect that when you take steroids, you're going to feel at least a little bit emotional. At minimum, for most people, they feel a little bit anxious, they have a little bit of trouble sleeping. And most of their feelings, whether it's sadness, happiness, excitement, anger, are going to feel like they got taken up a notch.

(12:17): If you're feeling overwhelmed, you can do things just to make your room quieter, more peaceful. You can dim the lights. You can make sure that just one visitor is around, somebody who's able to sit and be quiet with you, or somebody that you feel safe, and if you're going to express a lot of emotion, they're not going to judge you or make you feel bad about it later.

(12:41): Patients should promptly report suspected side effects from steroid use to their doctor. And of course, if you start feeling excited or distressed to the point where you really can't take it, where you're feeling that you can't sleep at all, or you're thinking that life is not worth living, if you're starting to think that your close trusted loved ones are no longer trustworthy, or anything sort of strange, you're going to want to let your doctor know right away.

(13:06): Steroid side effects may be lessened by changing the dose or switching to other medications. So what else should you do? So, in that scenario, it is not necessarily feasible for your doctor to completely stop your steroids, because if you're taking them for graft-versus-host (GVHD) disease, there may be no good other choice. However, the schedule of steroids sometimes can be changed so that you take them first thing in the morning and then mid-afternoon, and that can help with not messing up your sleep as much as it would if you took the steroids in the evening.

(13:34): Sometimes you can take other medications to counteract the effects of steroids. Zyprexa® is one example of such a medication. It's often used for nausea and appetite in patients who are going through transplant and other types of cancer treatments. So, there are ways to counteract the effect of steroids. Sometimes it may require that you be in the hospital to be fully safe. You may be able to have the oncologist or a psychiatrist come visit you to advise you about how to reduce the risk, keep your environment calm and treat any other symptoms like anxiety, insomnia, or distress that you're experiencing.

(14:22): What are the other common medications used in transplant that can affect your brain function? Well, there are lots of medications in transplant, so I'm going to go through them category by category, reviewing some of what has been seen and which ones are most common. On all of these slides, I have bolded the most frequently occurring psychiatric side effects, and that way you can quickly take a look at the slides and know which ones are most often occurring.

(14:55): Several antibiotics, antivirals and antifungals can cause psychiatric side effects, especially Voriconazole. So, antibiotics, antivirals, and antifungals are very common, even as prophylaxis for transplantation. And several of them have a lot of psychiatric side effects.

(15:09): Voriconazole (Vfend®) is far and away the most common cause of very concerning psychiatric side effects. Patients experience auditory and visual hallucinations on voriconazole (Vfend®). Usually, patients know they are hallucinating. They will actually report "I'm seeing things that aren't there", but it can be quite distressing.

(15:32): Posaconazole (Noxafil®), which is often what we switch to, can somewhat cause confusion and psychiatric side effects, although much less commonly and less intensely than voriconazole.

(15:45): Cipro®, another common antibiotic, can cause mental excitation that's not like enthusiasm. It's like feeling too amped up, kind of like what we talked about with steroids, poor sleep, feeling dizzy.

(16:02): Cefepime (Maxipime®) can cause delirium and clarithromycin, Bactrim and Valtrex also have some risk of causing delirium.

(16:09): Delirium or confusion is a common response to some medications used in transplant patients. Every time I write delirium here, it basically means confusion, being out of it. Some people might feel like they're out of it at certain parts of the day, and other parts of the day, they're feeling themselves. But this is an extremely common syndrome in patients getting cancer treatments, and that makes sense when you see how many of the medications can partially contribute.

(16:36): Medications for delirium may cause helpful sedation but also further impair thinking. Okay, so now medications for symptoms. Nausea medications, although they may have positive effects, depending on whether you're having anxiety or insomnia, can often cause more sedation than intended. So Ativan®, Zyprexa®, Remeron®, Compazine®, all of these medications can cause sedation. In some cases, you may like a little bit of sedation, and there's nothing wrong with feeling a little bit more relaxed and being able to take a nap. But it's also important to realize that they can impair your thinking.

(17:08): Opiate pain medication, of course, also causes sedation and sometimes confusion, typically more confusion than the medications that I've listed here for nausea.

(17:17): Keppra®, which is for seizure prophylaxis, can cause almost any different type of psychiatric symptom, because it can change patients' personality. And any time I see someone on Keppra, and they're acting in a way that the family says is not their normal personality, I suggest that the team consider changing to Depakote or Dilantin, which are also for seizure prophylaxis.

(17:42): Several chemotherapies can change brain function including insomnia, mood changes, and delirium. So here are some chemotherapies that contribute to changes in brain function, Cellcept® being the most common. As you can see, Campath®, Cellcept®, and busulfan all can cause insomnia and Bulsulfan can cause mood changes. The rest of these agents can cause delirium, which is medically induced confusion, and can be anywhere from just not knowing the correct date to not being able to recognize where you are, why you're in the hospital, and being truly distressed. So how much of a concern this is depends on how confused and how distressed you get with your delirium.

(18:22): So, I've given you all this information about medications that you may have no choice but to take and telling you that they can have psychiatric side effects that you obviously don't want to have. So, what can you actually do with this information that's useful?

(18:39): Knowing what to expect can be helpful for people with chemobrain or steroid usage. I believe that knowing what to expect really can help people stay calm, even when the symptoms are taking place in your brain. When you go into steroid treatment, knowing that when you are taking steroids, you may feel more emotional, that's not information you'll forget, just because you're having a psychiatric side effect. It doesn't mean you won't remember, 'oh, that doctor I saw talk at the survivorship symposium said that this happens all the time.' For a lot of people, just knowing that it's common, knowing what the cause is, and knowing that it's probably going to resolve on its own really helps, even in that moment of feeling distress.

(19:19): Caregivers can also help identify symptoms of chemobrain or steroid side effects in transplant patients. For the caregiver, of course, knowing what to be looking for that might be related to the chemotherapy treatment or the antibiotics is important so that you can apprise the team if you see any of these symptoms come up.

(19:35): You can consider asking for Namenda or thiamine for potential protection against these problems. These are not well proven treatments for chemotherapy related cognitive impairment, but they are very low risk.

(19:48): Oncologists should know of any previous psychiatric history while treating cancer patients. You should make sure that your oncologist is aware of any previous psychiatric history you or your family has, or other risk factors, so that the oncologist can be vigilant about any psychiatric symptoms and changes and can call a psychiatrist or health psychologist for assistance in your care. And now I will take questions. Thank you.

(20:14): [Steve Bauer]: Q & A. Thank you, Dr. Mishkin, for this excellent presentation. We will now begin the question-and-answer session. Our first question is: Can you speak to the effects of steroid creams used for localized GVHD? I seem to be experiencing some of these symptoms, such as agitation and anger, but only for about 24 hours after using the cream.

(20:53): [Dr. Adrienne Mishkin]: Hi, thanks for that question. That's interesting. You would think that something you put on topically would not affect the inside of your body. But actually, we do absorb everything we put on our skin. Even sunscreen gets absorbed into your body. It's not as common to have psychiatric side effects from topical creams with steroids in them as it is from ingested or IV medications, however, it is possible. There are reports of that happening.

(21:26): I think it's more common with the very strongest types of creams, but the one they sell over the counter, I want to say it's cortisone 1% or 2%, which is sold as an over-the-counter steroid cream, you would not expect to cause psychiatric side effects, unless you ingest it. But with some of the stronger ones like Betamethasone cream, something that you would be taking for GVHD, yes, it's definitely possible for that to be absorbed, and therefore to cause internal side effects.

(21:59): [Steve Bauer]: My daughter is on Keppra® and Cellcept®. What can be used to help with insomnia?

(22:10): [Dr. Adrienne Mishkin]: It's hard for me to make a specific medication recommendation without seeing the entire list of a person's medications and condition, so this is not direct medical advice. But Keppra® and Cellcept® do not rule out any of the typical medications that are used for insomnia. So, I wouldn't change typical recommendations. Things like Ambien®, Benadryl®, Trazodone®, Belsomra®, all of the medications that are commonly used for sleep, could be considered in the same way that they would be if she were not on those particular medications.

(22:54): [Steve Bauer]: Is there any connection between GVHD and dementia?

(23:02): [Dr. Adrienne Mishkin]: So, this is a great question, and there are two different parts that I'll speak to. One thing is that it is actually possible is to have GVHD that directly affects the brain. This is so uncommon that there is no actual data to say that having an episode of brain GVHD causes chronic problems for the brain, none that I've found at least. I've only seen two patients with brain GVHD, and I've only had one patient recover. So, the long-term data are yet to be determined.

(23:47): However, GVHD, in general, is treated with steroids. And steroids do contribute a small amount to chronic cognitive changes. For approximately 7% of patients who have cognitive changes from their steroids, those changes will be permanent. The vast majority of people recover from any brain fog related to steroids. Some people do have chronic damage to the brain that results in dementia, but this is a very small percentage and it's something that, if you're not actually experiencing any symptom of that, it's not something I would say in the long run you should be worried will happen later. If you have GVHD, and you're taking steroids for GVHD, and you're already having some cognitive symptoms associated with those steroids, those are the patients that I would say should be concerned and seek additional medical advice about that topic.

(24:51): [Steve Bauer]: I'm four months post-transplant and I definitely have chemobrain. Will this be lifelong or will it go away? My transplant was for AML.

(25:05): [Dr. Adrienne Mishkin]: At four months post-transplant, you're probably still having a combination of factors affecting your focus. So, you may be having exactly the syndrome of chemobrain, but that doesn't mean the only factor is the chemotherapy itself. You're probably still on some kind of immune suppression or steroid. You're probably on some prophylactic antibiotics and possibly prophylactic antivirals. Some of those slides that I was showed each item separately, so people may ask " Does this particular treatment contribute to confusion or dementia?" But in reality, most people are not taking just one of these medications. Most people are taking these medications in combination. So the part that is from the chemotherapy, strictly speaking, is probably mostly irreversible, it may improve a little bit over time. But the effects that are from steroids, 93% of the time, reverse later on when you're off steroids. The effects that are related to antibiotics, antivirals, or antifungals will mostly improve. The effects that are just related to fatigue and having been sick for a long time will improve.

(26:26): So, for most patients who are several months out of transplant and experiencing these symptoms, technically, the part from the chemotherapy may not get that much better. But a year from now, would I expect you, overall, to feel less burdened by those symptoms? Yes, I would, because it's not really just one thing.

(26:49): [Steve Bauer]: Do you recommend any type of activities to stimulate repair of the damaged neurons?

(27:03): [Dr. Adrienne Mishkin]: No. I don't think that you can actually repair the specific damaged neurons. We know that people can beef up some parts of the brain. Whether you could work on those specific parts...I think people like the idea that they're fixing the part that's broken. But the healthy parts of your brain are probably easier to strengthen. So, it's just like my example with language versus math. Or, if I hurt one my ankles, I might wish that ankle was better, but actually working out the healthy ankle is likely to make it strong enough that I can actually walk because I'm leaning on the healthy side.

(27:46): So I think any of these exercises with cognitive retraining or doing all the things people should do as they age, doing crossword puzzles and reading and just using the rest of your brain, can strengthen the other parts so that you're more able to function, even though there may be one part that still does not work exactly how it worked before. And again, we're talking about parts working slower than normal, not that they can't work at all.

(28:16): [Steve Bauer]: I've had mania from prednisone in the past. Does that mean it'll happen again if I need to restart prednisone?

(28:30): [Dr. Adrienne Mishkin]: Not necessarily. Anyone can have mania from prednisone, and it might depend on whether something like that has ever happened to you before in another context. But my recommendation for a patient who specifically had that happen before would be, if they need to start steroids again, that the steroids be given together with a small dose of Zyprexa®. When people Google Zyprexa®, they're going to say, "That psychiatrist told me I need an antipsychotic," and technically that is what it originally was for. But it's quite effective for mania. People with psychosis, for example, schizophrenia, might take 30 or 40 milligrams in total a day.

 In patients with cancer, we usually give something more like five milligrams at night and it helps people sleep. It helps with nausea and appetite. And it helps to protect you against something like mania or confusion. So, the safest plan would be, if you need steroids again, to take them together with something that balances things out so that you don't wind up manic again.

(29:41): [Steve Bauer]: Has meditation been studied as a useful tool to improve cognition post-transplant?

(29:54): [Dr. Adrienne Mishkin]: Not that I'm aware of.

(29:55): [Steve Bauer]: After transplant in June 2022, I started on a maintenance treatment, with Revlimid in September ,and then got chemobrain in February of 2023. Is it common for chemobrain to take that long to kick in?

(30:22): [Dr. Adrienne Mishkin]: Yes. So strangely, people do often have these side effects starting later on. I don't have a great explanation for why that would be. Some of it might be that, early on, the patient is just sick, and so everyone assumes it's due to their illness. But we do know there's some evidence, for radiation specifically, that even patients who are evaluated quite specifically for what's happening cognitively, sometimes do have symptoms that start six months or even longer after the radiation. This may be more hard science than my practice. I'm a clinician. I see patients all day. But this is very common, even though it seems totally counterintuitive.

(31:14): [Steve Bauer]: Are brain games beneficial in improving chemobrain and memory loss?

(31:20): [Dr. Adrienne Mishkin]: So yes, brain games can be. But again, what you're targeting, really, is making sure that no other part of your brain goes unused. The idea of doing brain games - Lumosity®, crossword puzzles, any of these things - is to make sure that you are using all the parts of your brain because the expression "use it or lose it," is actually true with the brain. You want to exercise all the parts of the brain that you can.

(31:47): If you just sort of stare at the ceiling or watch a lot of TV (and sometimes when you've been sick, people might even encourage you to do less stuff) that might feel right when you're recovering. But it is good to use all of your brain. But are you necessarily really recovering the part of the brain that got affected by cancer, or are you just strengthening everything else so that your total functioning is better? I think it is more likely to be the latter.

(32:19): [Steve Bauer]: Are there any apps, programs, et cetera that a stem cell or bone marrow transplant patient can use to help with chemobrain caused by the heavy-duty chemo used with transplant patients?

(32:36): [Dr. Adrienne Mishkin]: So again, the kind of program that I would recommend is called cognitive retraining. And I think it is something you have to do with a professional. I'm not aware of an online do-it-yourself cognitive retraining program because some of it really has to do with assessing what parts of your brain are working best, what's easiest for you, and what parts are harder. Without somebody else looking from the outside of your brain, it would be very difficult to do that on your own. It's not only super specialists or sub-specialists like me who can do this. A psychologist can do this and there is physical therapy, occupational therapy offices that also offer some cognitive retraining. So there are lots of options of ways to get this type of treatment.

(33:28): [Steve Bauer]: Does COVID add to the chemobrain effects, or does it present differently, even if someone has not been given Dexamethasone for COVID-19 treatment?

(33:45): [Dr. Adrienne Mishkin]: So, I'm not sure if your question is about COVID versus chemobrain or if it's about COVID and chemobrain, so I'll answer both. I'll answer the latter first because it's simpler. There are not yet good studies of patients who've had COVID and chemotherapy and any additive effect. But there are lots of reports comparing COVID's cognitive effects to chemobrain, and the reports are very similar. Reports of the cognitive symptoms associated with chronic inflammatory illnesses, such as chronic fatigue, or some of these newer syndromes, even mom brain, are similar.

(34:36): It's the sense that you cannot quite think of the word you want as quickly as you normally would, or that maybe it even takes a few minutes to think of that word. It could be that you go into a room and then you can't think of exactly what you were planning to do and it takes you a few minutes to remember, but it doesn't necessarily get worse over time like dementia would. In true dementia, you would have symptoms like that, and a year later, you might be confused on a much larger scale.

(35:09): These syndromes, the symptoms don't really change very much and they don't progress to personality changes, or not recognizing people, or anything like that. So, we think that these are probably similar syndromes because they're the effects of general inflammation in the brain. But there are not data to say that if you get COVID and then have chemotherapy, or vice versa, what the additive presentation is expected to be.

(35:40): [Steve Bauer]: Okay. Our next question' comes from a long-term survivor. How does total body irradiation along with chemo and Prednisone affect the brain? I am 28 years post-transplant, have been off all meds related to BMT for 27 years.

(35:58): [Dr. Adrienne Mishkin]: Wow. That's a long time. That's great. I'm not sure if that information at the end was part of the question or just letting us know. Certainly, after 27 years, whatever side effects you had back then would be what they are. I wouldn't expect them to change now. The radiation probably had the single worst effect on the brain, of those things that you mentioned. People who have irradiation that includes the brain usually do have some kind of permanent cognitive deficit. And they're not always only in the category that I mentioned in terms of chemotherapy. You're asking: What about combining those three things? I think in this world of post bone marrow and stem cell transplantation, pretty much everyone who got brain irradiation also got chemotherapy and some type of immune suppression, if not exactly steroids, something related to steroids. So, I think all of our data are really referring to patients who have had all three. And I would say, typically, after brain irradiation, you do see some cognitive changes for a lot of patients, more than half, I think.

(37:19): [Steve Bauer]: Are there any books that you can recommend for emotional health when facing chronic illness?

(37:31): [Dr. Adrienne Mishkin]: That is a big question. Honestly, I hope that this is not a cop out, but I don't think that there is any book that I would recommend universally. When I recommend a book to a patient, it's usually because I really think that the author of that particular story, or memoir, or document, would connect with that particular patient and their perspective. And I don't think that there are good "one size fits all" narratives that equally apply to everyone. Actually, one of the things I always worry about, because I treat almost exclusively bone marrow transplant, cellular therapy, and stem cell transplant patients, is that if you read a memoir by someone who had a much less lethal type of cancer that sometimes they can be sort of overly positive in a way that's sort of unfair.

(38:37): A lot of memoirs are written by breast cancer survivors who have been through plenty, but it's not necessarily applicable to someone going through a stem cell transplant. So often, the literature that's available is less applicable when you have a very unusual diagnosis or you're going through a very unusual condition. I cannot say that I've located literature that I believe applies to all of the patients in general.

(39:09): [Steve Bauer]: Are there any psilocybin treatments for anxiety, depression, et cetera after a bone marrow transplant?

(39:20): [Dr. Adrienne Mishkin]: So, psilocybin is really still being researched for use for psychiatric symptoms. I'm sure lots of people listening to this presentation were part of research when they were getting their cancer treatments. But when it comes to treatments that are under research for things other than cancer, a lot of the time, cancer patients are actually excluded from the research population because researchers are trying to look at the treatment in an isolated way.

(39:57): So, psilocybin is a good example of where, at this point and time, they would still only be testing it in patients who have essentially no other medical comorbidities. They would also probably be testing it only on people who are severe sufferers of depression. Most people who have had a major medical problem and go on to have depression, even if they might be just as depressed, would be considered a different syndrome of depression related to adjustment to illness or something like that.

(40:29): So, I think that research for patients with cancer will come only if depression and anxiety are successfully treated, in an isolated way, with psilocybin. To be realistic, patients who've had bone marrow transplants would probably not be recruited and while they might not be excluded from the research, they probably wouldn't be specifically studied until there was evidence created specifically for cancer and depression.

(41:00): So unfortunately, once you've been down a path of having this unique treatment, it means that the data that you might want to have for patients like yourself may take even longer to create because first, they have to prove that it works. Then, they must prove it works in cancer. Then, they must prove it works in cancer after a particular treatment.

(41:26): [Steve Bauer]: Does chemobrain eventually clear in most patients? And how long can chemobrain last after the treatment has ended?

(41:44): [Dr. Adrienne Mishkin]: Yes. So, it depends on your age and your neurological functioning prior to getting chemotherapy. The range is wide. I would say, for the vast majority of people, they feel it is not fully reversed later. Younger patients are sometimes able to recover more of their cognitive functioning. There was one poster I saw a few years ago that showed a series of patients who were transplanted around their early 20s who did actually recover cognitive functioning, at least on testing.

(42:23): I think the answer's sort of somewhere in between. You might not have the exact cognitive functioning you would've had if you'd never had chemotherapy, but more than half of patients do not have the full cognitive functioning they would've had without chemotherapy. And more than half the patients with cognitive changes are still very much able to function, sometimes by using these compensatory strategies that I described before, such as "I know that I tend to forget things, so I just write them down" or "I know that I can't always think of the word off the top of my head, but I know I can just describe my way around what I want to say". So, it doesn't necessarily affect them in their lives as much as it initially seems like it's going to.

(43:12): [Steve Bauer]: Is my occasional aphasia seen in patients who have had chemo to the brain?

(43:19): [Dr. Adrienne Mishkin]: Yes. Trouble finding words is the single most common complaint.

(43:29): [Steve Bauer]: Okay. This is a little longer question, but here it goes. I am an AML patient and had a BMT seven months ago. For the first six months, I was mostly focused on just getting through the day with constant nausea, digestive issues, and other physical challenges. Once I began to feel physically better, I started to suffer anxiety about the remaining relapse risk and flashbacks of the struggles I experienced while being hospitalized, something like PTSD. Is that common? And what can I do to help myself?

(44:10): [Dr. Adrienne Mishkin]: Yes, that's extremely common. So, I'll tell you a little bit more about my role. I evaluate patients coming in for allogenic transplantation at my center, and anyone else who wants to. And I'm available to patients who have gotten any type of transplant through video visits after their transplant has happened. And I also see patients in the hospital. There are a good number of patients who, after they met me once for their pre-transplant clearance, never want to see me again. They don't feel that they need anything. And then I hear from them six months, 12 months, or sometimes even 24 months after transplant. And I think it's exactly what you're describing in your question, that when you start to feel physically better, that sometimes is the moment when you suddenly start to mentally let in everything that's happened to you. Or maybe in your mind, you thought, "Okay, I can handle this for six months, or I can handle this for a year." And when you don't feel 100% back to normal at that time point, the significance is very different.

(45:26): So yes, 100%, starting to get anxious about what's happened to you six months later is very normal. And you can't even really say whether it's post-traumatic stress, yet, because in a way, it's still going on. This may be the moment that you finally feel well enough to really absorb everything that's happened and start to process it. You may have the symptoms of PTSD, but technically, PTSD is post, so that's why I phrased it that way.

(45:57): I think that this is really the time to speak with a mental health professional. Right? Obviously, I'm a psychiatrist, but listening to me for an hour or whatever this is, is no replacement for getting your own treatment. And I know that seeing a psychiatrist has all kinds of different meanings to different people, and depending on where you're located geographically and what kind of insurance you have. It may be feasible or not. But there are other types of professionals who can serve the role of helping you process what's happened.

(46:30): There are a lot of social workers who have private practices where they do therapy. There are nurse practitioners in psychiatry. There are psychologists. And sometimes if you're in a location geographically where none of those things are available, there's probably some experience on your primary team of talking with patients about their experience as well.

(46:52): If you're feeling like you might have post-traumatic stress, or you might be headed towards post-traumatic stress, then I think it's extremely important not to be alone with that and not to assume that your family can help figure out what to do. Instead, reach out to your medical providers and ask for their input. There are, of course, some doctors who are not psychiatrists who just go straight to, "Here, have an Ativan," and that's not usually what I would recommend. But just talking with your oncologist about things like "What is the risk for relapse? When do people start to feel like this is over?" For most diagnoses, around two years is when the doctor starts to feel more relaxed that you're not really going to relapse.

(47:45): Even if your oncologist is not the kind of person to be giving you therapy, you can still have a discussion with your oncologist or their staff about when will they start to feel more relaxed, and when do patients usually stop worrying, and what can be done to help you manage those feelings.

(48:06): Maybe you could have your labs done more often, or less often, depending on which makes you more anxious. Some patients want their labs done more often so they can feel reassured they're not relapsing, or other things like that. If it's possible to get into therapy, to really talk about all those feelings, I think it's very valuable.

(48:28): I spend 50% of my time just with one bone marrow transplant program supporting those patients. I know not every program has that, but every program should have someone they can refer you to in the area, because it's really important to talk about what you've been through, not only with your family, but with a professional who can listen objectively and advise you.

(48:55): [Steve Bauer]: Do you have any statistics or flowcharts on how to discern between CAR-T neurological side effects versus the [inaudible 00:49:07] and steroid toxicity side effects you covered in your slides?

(49:12): [Dr. Adrienne Mishkin]: So, the side effects of the CAR-T are really completely, completely different. The time course, first of all, is extremely different. So, in the first week after a CAR-T, the cytokine release syndrome, it's not something that could happen. It's what happens. People have headaches, nausea, trouble breathing, body pain, and just feeling crappy. So that's the expected side effect that starts about a week after CAR-T.

(49:52): Then there's something called ICANS, which happens in the first month after CAR-T. This is going to happen in up to 62% to 67% of patients, depending on their primary diagnosis. We have leukemia patients being affected slightly more often than lymphoma patients. This causes an expressive aphasia. That means when people talk to you, you know what they said, and when you talk, you can't get your words out. Some are dysgraphia, which is where your handwriting gets tiny and weird, and lethargy, which doesn't just mean feeling like sitting on the couch. It could mean you can't even be woken up fully. It can progress to global aphasia, meaning you can't speak at all, seizures, being obtunded, which means we can't wake you at all, or even a coma, which is very rare in comparison, but can happen.

(50:47): The treatment for this is steroids. Patients who have ICANS and are treated right away with steroids, they pretty much wake up within almost one to two days. So, this a very different syndrome that's more on the neurological end, where people actually can be unconscious, can be unable to speak, can have seizures. But we work with neuro-immunology most of the time for patients who are having post CAR-T side effects.

(51:24): [Steve Bauer]: After long-term dosage of prednisone, I was prescribed Zoloft®. I'm no longer on prednisone but haven't stopped the Zoloft®. How might this be affecting me?

(51:42): [Dr. Adrienne Mishkin]: Well, it depends on the dose of Zoloft® and whether you need it. In terms of side effects from Zoloft, the main long-term side effect of SSRIs is decreased libido, meaning a decreased interest in sex and a longer time between starting a sexual act and being able to have an orgasm. About one in three people, regardless of sex and gender, will have sexual side effects related to an SSRI. Other than that, the side effects are pretty idiosyncratic. There are people who poop a lot more often when they take Zoloft than when they don't. There are some people who poop less. People get hot. Some people get sweaty, but not necessarily hot.

(52:27): But most of the side effects are pretty subtle and pretty much individual. And for the average patient who's been on Zoloft for more than six months, the only side effect you would expect would be decreased libido. So, whether you actually need Zoloft or not is I think a different question that I can't really answer based on the information you've given.

(52:49): [Steve Bauer]: I'm sorry. He also stated 50 milligrams of Zoloft®, if that has any effect.

(52:56): [Dr. Adrienne Mishkin]: 50 milligrams of Zoloft® is a low to medium dose, so a full dose of Zoloft® is 200 milligrams, and a baby dose would be 25. If you did want to get off of Zoloft, I cannot tell you whether that's safe for you or not based on not knowing your psychiatric history. I can tell you that there is no withdrawal from Zoloft®, so even if you just stopped it, most likely you would have no withdrawal at all because it self-tapers over the course of several weeks. If you wanted to decrease 25 milligrams, there would be nothing biologically dangerous about doing that on your own. But of course, I don't know whether you've had any psychiatric risks such as having suicidal thoughts or anxiety that would prevent you from being able to take care of yourself or anything like that. So, I cannot advise you about whether this is a good idea, only that from a biological perspective, that's not a medication that needs a lot of tapering.

(53:56): [Steve Bauer]: Closing. On behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Mishkin, for a very helpful presentation. And thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way.

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