Sleep in Transplant: More than Just Getting Your Z's!

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Sleep in Transplant: More than Just Getting Your Z's!

Sunday, April 30, 2023

Presenter: Timothy Sannes PhD, MS, UMass Memorial Hospital

Presentation is 40 minutes long with 18 minutes of Q & A.

Summary: Problems with sleeping can exacerbate the fatigue and depression that often accompanies a stem cell transplant. This presentation reviews many sleep issues like insomnia that can complicate recovery after transplant, and describes effective remedies for these problems.

Highlights:

• Problems with sleep can affect memory, thinking, concentration, and moods. Poor sleep can weaken immunity, raise blood pressure and affect all organ systems.
• Cognitive behavioral therapy for insomnia (CBT-I) is a structured program of multiple sessions to treat sleep problems. Cognitive behavioral approaches have proven more effective than medication for treating insomnia,  and are the recommended by American College of Physicians as the first line treatment for insomnia. 
• Sleep issues can often be improved by using the bed only for sleep or sex, restricting daytime naps, and maintaining a consistent bedtime and waking time.

Key Points:

(04:36): Many people do not regularly get the recommended seven hours of sleep per night.

(07:49): Insomnia is defined as recurring problems initiating sleep maintaining sleep or awakening too early for an extended period of time. It must also cause distress or impairment in the rest of our lives.

(12:31): Sleep problems may persist even after depression and anxiety improve.

(15:30): Stem cell transplant recipients often report sleep problems before, during and after transplant.

(17:11): Post-transplant sleep problems may be associated with peripheral neuropathy, restless legs, and chemotherapy.

(19:39): Cognitive behavioral therapy for insomnia (CBT-I) is a structured program to treat sleep problems.

(21:35): Sleeping pills like hypnotics have risks that need to be carefully evaluated before use. Extended use of hypnotics for sleep issues can increase the risk of other health problems.

(25:37): Alcohol, caffeine, and smoking can cause sleep problems.

(29:09): Leaving the bedroom for a relaxing alternative if you cannot fall asleep can be helpful.

(30:47): The blue light of cell phones is “activating” (stimulating) and counterproductive for good sleep.

Transcript of Presentation:

Note: In this presentation, when the speaker uses the term bone marrow transplants, it includes stem cell and cord blood transplants as well.

(00:00):  [Marsha Seligman]:  Introduction. Hello everyone. Welcome to the workshop, Sleep in Transplant: More than Just Getting Your Z's. My name is Marsha Seligman and I will be your moderator for this workshop. It is my pleasure to introduce today's speaker, Dr. Timothy Sannes.

(00:16): Dr. Sannes is a clinical health psychologist and an attending psychologist at UMass Memorial Hospital. He is also an associate professor in the Department of Psychiatry at UMass Chan Medical School. Dr. Sannes provides flexible evidence-based support for cancer patients and their families. He has extensive experience in sleep medicine and has conducted research in daily hormonal rhythms and wellbeing. Please join me in welcoming Dr. Sannes.

(00:50): [Dr. Timothy Sannes]:  Thanks so much, Marsha. It's great to be here on this virtual platform. I can't see everyone's face but suffice to say that I'm here on a sleepy day in Massachusetts. It's raining but I'm not going to reference naps or anything I have in my future.

I'm really, excited to be here and talk to everyone about a topic that I'm really passionate about, and talk with many of my patients about, which is sleep. So, let's jump right in.

So, like Marsha mentioned, I'm an Associate Professor in the Department of Psychiatry at UMass Memorial Chan Medical School. And I see folks both before, during and after treatment, primarily, bone marrow transplant. So, this is an area I've been in for several years.

(01:53): Overview of Talk. Our learning objectives today are to talk about the consequences of poor sleep on health, what constitutes enough sleep, and then talking more specifically about hematologic stem cell transplant. And then, finally, what we know, in evidence-based in terms, about what is effective for falling and staying asleep, and improving sleep quality.

So, I'll go through that based on the following outline and talk about why, in general, we care about sleep, and then explain the difference between true clinical insomnia and just disturbed sleep. I'll talk about wat we know, in broad terms, about cancer and the unique challenges in stem cell transplant. Then I'll send you out of here with a couple of basic evidence-based treatments.

(03:18): So, how much sleep do we need? This is probably a question that some of you have had in the past. And to be quite honest, there's not one number. So, everyone is different, which is never a very satisfying answer. But you can see here that the National Sleep Foundation has put forth recommendations around the general differences across age groups.

(03:48): Experts concur that adults need around seven hours of sleep per night. And quite interestingly when we asked the question 'how much sleep do we need?' the National Sleep Foundation assembled a group of experts in 2015 to come up with the number seven. So, most individuals need around seven hours of sleep, in adulthood, to achieve restful sleep.

Of course, those of you that have children know that kids, both newborns all the way up to school aged children ,often need more sleep. And there are clearly barriers to how we allow sufficient sleep to happen in our busy everyday lives. But suffice it to say that seven is a general number accepted as the minimum number of hours of sleep needed for restful high sleep quality.

(04:36): Many people do not regularly get the recommended seven hours of sleep per night. But what do you know? A lot of folks don't get that. And this heat map shows, across the country, estimates of the percentages of people that sleep less than seven hours per night.

So, this map is quite similar to maps of other health problems, such as diabetes, obesity, heart disease, there's a quite similar geographic pattern. And so, are the two related, in terms of poor sleep quality, sleeping less than seven hours? I would guess that they are, but you can judge for yourself. You can see that overlapping trend in the southern rust belt, whatever that general geographic trend is of poorer sleep across the country.

(05:33): Lack of sleep can affect memory, thinking, concentration and mood. And so, what are those health consequences? Why is sleep important?

Probably many of you in this audience have had a few nights of poor sleep, if not worse. And so, you've probably experienced some of those issues that are at the top of the slide. After a poor night's sleep, you may have trouble with memory. You may notice your brain isn't functioning at quite the same level in terms of thinking and concentration. You might notice you're a little bit edgier, some mood changes. These are all again backed up by pretty rigorous studies. People who have poor sleep have a higher risk for accidents, in general, that includes car accidents, that includes accidents at work.

(06:15): Poor sleep can weaken immunity, raise blood pressure, and affect all organ systems. And then, we get into the real health consequences. So, obviously, relevant to cancer, there's weakened immunity. Even after one night's sleep, there's a robust impact on the immune system. Higher blood pressure with poor sleep is also a known relationship.

And poor sleep cuts across almost all organ systems. We know that poor sleep is associated with weight gain, risk for diabetes, low sex drive, heart disease, poor balance.

And there are even more stark findings in terms of health consequences, such as increased risk for cancer, and an increased risk for suicide. So, I didn't put those on this slide, but pretty extreme outcomes of poor sleep that have been observed across the research literature.

(07:21): Sleep problems are getting worse over time. Unfortunately, this is getting worse. This is a little bit of a dated slide, but I've seen more recent estimates that adults reporting one or more symptoms of a sleep disorder - not insomnia - I'll get into that in a second - is, across time, getting worse. So, this is one or more symptoms of a sleep disorder, poor sleep, and I'll break that down here in a second.

(07:49): Insomnia is defined as recurring problems initiating sleep, maintaining sleep, aor awakening too early for an extended period of time. So, what are we talking about when we talk about sleep problems? I've talked about the general importance of sleep, that it's not great across the country and it may be getting worse. But those are really around sleep quality. To meet criteria for insomnia, individuals have to have more problems than just waking up tired many days in a row. You must have one of the top bullet points. The first is difficulty initiating sleep, maintaining sleep or having early morning awakenings. And those have to occur for at least three nights for at least three months. Basically, this occurs despite having an adequate opportunity for sleep. And there are a couple other bullet points, that we won't spend a lot of time on, that basically these sleep problems are not attributable to something else.

(08:41): So, something that is incredibly important is medical evaluation, is making sure that things like obstructive sleep apnea or restless legs are ruled out, which obviously have an impact on sleep.

(08:56): Insomnia can cause distress or impairment in the rest of our lives. But I put the last bullet point in italics, because pretty much every "disorder" that we psychologists have is always predicated on fact that the symptoms someone experiences are impacting their life, and that's what clinically significant distress /impairment means. So, several folks in this audience have probably had sleep problems that actually crossed over and affected their lives, and that's always our threshold.

(09:30): In insomnia, the person has the opportunity to fall asleep, but their ability to either fall asleep, or stay asleep is reduced and they may have early morning awakenings. I mentioned sleep opportunity. This is not the same as ability to sleep . Essentially in insomnia, individuals have the opportunity to sleep. They have the eight hours available in the evening. They're not shift workers driving through the night. They're not someone, like me, with a newborn who has very few hours available. Whereas someone with just sleep deprivation really doesn't have the opportunity to sleep. But if they did, they would be able to take advantage of it, and I think that's an important distinction.

Then, what about cancer? Obviously, that's one of the reasons that we're here. It's one of the areas I specialize in. And I think it's really, important to think about how complex this problem is.

(10:30): Insomnia has significant overlap with daytime fatigue and depression So, this is a Venn diagram from a few years ago, but I think it starts to highlight that this is multifactorial.

And on this slide, we have fatigue, depression, insomnia. But I suspect there' are several other overlapping bubbles that are related to one's wellbeing. So, we talk about quality of life for instance. We talk about anxiety. And that's not on this slide but suffice to say that insomnia has significant overlap with daytime fatigue and significant overlap with depression.

And in fact, the relationship between depression and insomnia or anxiety and insomnia is one that's hotly debated in my field in terms of which comes first. If you treat sleep, can you actually just improve depression without doing anything else?

(11:28): Cancer is also associated with elevated fatigue and depression in cancer. And these are academic questions. But I wanted to highlight this because in cancer, we know that fatigue is common. We know that cancer patients have higher rates of depression than the general public, and so it's not a huge surprise and insomnia is following that trend.

The other piece of this slide is that there are a lot of other factors that impact these domains that cancer patients experience. And so, you can see some of those such as pain, body mass index, not coping well with significant life stressors, such as cancer.

And then, there's the biological factors, things like inflammation that are often treatment-induced. There's a lot behind the story and we're just really talking about the problems with insomnia today. But I think this highlights that this is a complex issue.

(12:31): Following cancer treatment, sleep problems may persist even after depression and anxiety improve. And so, when folks go through cancer treatment, they often experience problems with high levels of distress, higher levels of depression or anxiety. But I wanted to put this study up there because this, along with several other studies, suggests those elements of wellbeing I just mentioned - depression and stress, anxiety - often improve after treatment. But this study, and many others, have suggested that sleep remains a problem after cancer treatment. So, even though folks may adjust to their lives, feel better about where things are headed, sleep seems to be something that remains an issue.

And so, this study wasn't specific to bone marrow transplant, but I think it really did a really good job of breaking out the time trend of before treatment and after treatment. And they also showed, in this study, that men were at higher risk of maintaining sleep problems if they had insomnia before treatment.

There are also some other demographic factors: not being married was related to having better sleep after treatment. We're still learning about individuals' risk factors and their sleep following cancer treatment, but obviously, this is BMT InfoNet and we're here to talk about transplant.

I want to highlight a couple things that we know about transplant, specifically. Even though we've learned a lot about sleep over the years, a lot of that knowledge is not drilled down to stem cell transplant.

I think that's important to highlight, because some of this slide, and what I'll talk about ,is really what in research we call descriptive. It just describes the problem. When I get into the second part of the talk about treatment, and what you can do about it, it's important to remember that not all the recommendations have been tested in stem cell transplant.

Some of what I'll share, I have to extrapolate or go outside of that what we know in the research, to hopefully improve sleep for many of you in the audience.

(15:30): Stem cell transplant recipients often report sleep problems before, during and after transplant than the general population. And what do you know? This is a prevalent problem in stem cell transplant. A lot of patients report sleep problems before transplant, even more during transplant. But then, it typically improves.

For those of you in the audience that experienced big problems with insomnia, I hope that it improved post-treatment. But there's a subset of patients for whom it really doesn't improve, around a quarter of patients, which is a little bit higher incidence than general population.

Within that subset, maybe 3% or so experience hypersomnia, so sleeping a lot more than we would like. This time trend may or may not match with your experience, but the idea is that sleep problems are pretty bad, they're particularly bad during treatment, and after treatment, they hopefully get back to a more normal rhythm.

In terms of medical factors. I put a silly joke on the right side of the slide because anyone who's been in the hospital knows it's not a great place to sleep. During transplants, there actually is some data around specific conditioning regimens and sleep, and I have those up here so you can look back to this slide. Those medical factors and treatments seem to be related to poor sleep.

(17:11): Post-transplant sleep problems may be associated with peripheral neuropathy, restless legs, and chemotherapy. Post-transplant, the medical factors that seem to be related to poor sleep are things like peripheral neuropathy, restless legs. Chemotherapy actually confers some risk of restless legs in some regimens, and so those, obviously, are medical factors that can have a huge impact on sleep.

(17:29): Steroid use can disturb sleep and increase risks of sleep apnea. For those of you that have had experience with steroids, they not only can disturb your sleep in the moment, but over time they increase one's risk for sleep apnea. So, these are medical factors that we know are important.

(17:56): In one study, sleep was impaired before transplant, but it improved, whereas fatigue remained. The first one really highlights this sleep problem quite well and talks about treatments. The second one  really highlights the idea that fatigue may remain even if sleep improves or isn't as impacted. Fatigue is a huge contributor to quality of life and that paper did a really good job of pulling apart fatigue and sleep. So sleep, according to this study of bone marrow transplant patients, was impaired before transplant, but it improved, whereas fatigue remained.

And so, that's the disentangling of what we know about the contributors to both fatigue and insomnia. That's a broad overview of why I think this is important, and potentially something that is impacting some members of the audience.

I tried to highlight the unique challenges in stem cell transplant. But what do we do about it? So, the behavioral treatment is where I spend a lot of time. It's not all I do with patients, but it is a very, very important and effective treatment.

(19:39): Cognitive behavioral therapy for insomnia (CBT-I) is a structured program  to treat sleep problems. I have background in and work with patients on a system called cognitive behavioral therapy for insomnia (CBT-I). This is a structured program. I always joke with the folks I see. We're not in the business of Freudian therapy, where we see folks every week for 30 years anymore. We try our best to have targeted evidence-based treatments for patients, and this is one of them.

This structured program is typically four to eight weeks, around six sessions. There's a large focus, particularly at the beginning, around assessment. That's a sleep diary where you will document how long it takes you to fall asleep, how long you were asleep, how many times you woke up, et cetera, et cetera, et cetera. You think about all the different components of sleep.

(20:37): Then, the other components of cognitive behavioral therapy for insomnia, or CBT-I, are listed there, I'll break those down. If you were to see someone like me, or a sleep specialist, and they were going to implement this, it is really like other medical interventions. We check blood pressure. If anyone has had heart challenges or issues in the past, you wear a monitor for an extended period of time. With sleep, we have you use a smart watch to report on your experience. That's incredibly important. Getting started with someone who might treat  you with CBT-I means you're going to have to fill out a lot of information around your sleep patterns.

(21:35): Sleeping pills, like hypnotics, have risks that need to be carefully evaluated before use. I understand that a lot of people have tried sleeping pills and have maybe asked the primary care doctor if there's any medication they can take for insomnia. I'm not a physician, I don't write prescriptions. As a health psychologist, I focus on the behavioral approach that we're discussing.

But there are these medications that you see advertised on television at times They're called hypnotics. They're easy to take, just like any pill. Theoretically, you can take it once a day, you can take it at night and they're widely available. And so, there are a lot of primary care doctors that do prescribe these.

But there are some risks involved, and that's on the right sideof the slide here. There are more than listed on this slide. We do know that there's a high risk of psychiatric disorders in people by taking these medications. Also, accidents that can come from lack of sleep can come from taking these medications, as well, which is a little bit scary.

(22:43): Extended use of hypnotics for sleep issues can increase the risk of health problems. There's some data that there's a risk of death and higher mortality by taking these medications for an extended period of time. And just to be clear, I'm talking about hypnotics, I'm talking about sleep medications. And there's some more recent data that shows hypnotics can increase the risk of cancer, which of course we would never want to do.

I put this slide up here to question what the long-term outcomes of sleep medication are. But how does this stack up to what I started with which is behavioral treatments?

(23:28): Cognitive behavioral approaches have proven more effective than sleeping pills for treating insomnia and they have become the recommended first line treatment for insomnia.  When they are compared head-to-head, you don't need to be a statistician to figure out the gist of the slide. Cognitive behavioral therapy for insomnia (CBT-I) is better. So, the total score, lower is better. The medication really doesn't add a whole lot. It's really the behavioral approaches that are driving the positive effects in this study, probably one of the better ones that have been done to date, comparing, over time, medication versus cognitive behavioral therapy for insomnia (CBT-I).

So this has led to CBT-I being the recommended first line treatment for insomnia. This is a busy slide and has a lot of acronyms. I don't need to go through all of those types of treatments on the left. You may recognize some of them, like sleep hygiene. I'm not going to spend time on paradoxical intention, it's basically trying not to sleep and actually pushing yourself to do that.

(24:42): CBT-I, at the bottom of the chart, is really the combination of the former four or five components. The data is clear, so much so in fact, that the American College of Physicians recommends cognitive behavioral therapy for insomnia as a first line treatment for insomnia. Compared to some other types of treatment, the behavioral treatment is really what should be implemented first. And so, again, I can break down some of these but we'll do that as we go through what CBT-I is made up of.

(25:37): Alcohol, caffeine, and smoking can cause sleep problems. These are several drivers of sleep problems. So, alcohol, not good for your sleep. Caffeine, drinking it after noon, during the day, doesn't help your sleep. Smoking cigarettes doesn't help. You've probably heard of these. And this is probably what we generally categorize as sleep hygiene. So, things that in general, don't promote good sleep.

You may have even talked to a primary care doctor that described these to you or gave you a handout about ways to just shift these behaviors and see if that improves your sleep. Exercise is one. Exercise, overall, helps sleep but if you exercise in the evening, it actually can harm your sleep. So, these are helpful tips.

But when we really get down to insomnia or really disruptive sleep problems, it's the bottom of this list that becomes super important and they really inform the components of cognitive behavioral therapy for insomnia.

(26:59): Stimulus control means using the bed only for sleep or sex and minimizing other activities in bed like watching TV.. Stimulus control. So, that is a complicated term. It sounds complicated but it's really basic. It's really that you use your bed for sleep or sex and that's it. I'm going to try to send you out of here with a couple tidbits that will maybe help you in your daily life, and this is one of them. Try to be honest around what you bring into the bedroom or the bed.

Some people have a TV right in front of their bed. It's comfortable. It can feel relaxing. It does not help your sleep. I can guarantee it. So, this is just one example of things that we can do in our bed other than sleep that can activate our stress system or our wakefulness, so that over time, our brain learns that the bed is where we do all kinds of stuff other than sleep.

And so, breaking these down even further in terms of the components of cognitive behavioral therapy for insomnia. So, I'm a big believer in making our treatments accessible for patients. And this is one where I feel like it's hard to implement.

But I want to be transparent. You can find a lot of this information online. And you may try some of it yourself to see if it makes a big difference.

So far I've talked about sleep hygiene, on the far left. I've talked about some of the recommendations that are fairly straightforward, things you would know based on healthy behavior.

The stimulus control, however, is a little bit more challenging. That's where I said only use your bed for sleep or sex.

(29:09): Leaving the bedroom for a relaxing alternative if you cannot fall asleep can be helpful. And the second piece there, which I've worked on with patients for many years, is leaving your bedroom when you cannot fall asleep. That is tough. It's a difficult one for folks to wrap their head around and incorporate into their schedule. We don't have time to get into where you might go, what you might do, but it's got to be relaxing. Popping yourself down in front of the television, more often than not, isn't as relaxing as people think it is, and is actually is quite activating.

(29:41): Sleep restriction or limiting sleep time can actually improve sleep. The components to the right on this slide are sleep restriction, where we recommend is that people spend less time in bed. It relates to what I was just talking about. It's restricting people's sleep time to the point where they get very tired. And what do you know? After that third or fourth night of sleep restriction, they really conk out on the fifth night.

And then, there's the other three on the right of the slide. Relaxation is just practicing ways to relax. Some data suggest it's helpful, but I don't think it treats insomnia. It's probably not as effective as cognitive things that we address, things like thinking about sleep, worrying about the ability to sleep.

We wrap up and we try to drive home these behaviors and help folks maintain these behaviors after our meeting. But I mentioned stimulus control, and I mentioned how we really should try to only sleep in our beds. Yet I still use my phone for my alarm clock.

(30:47): The blue light of cell phones is activating and counterproductive for good sleep. I'm guilty, every now and again, of looking at my phone in bed, so I get it. I understand that our phones are, on some level, addictive. And what do you know, they also put out blue light. Blue light is known to activate the sympathetic nervous system, the awake part of our body. So, when we pull those phones out, not only are we fighting against our ability to avoid thinking about social media or politics or whatever we pulled up, but we're also actually physiologically challenging our body to relax ,because the blue light is activating.

(31:28): Worrying about not getting enough sleep can make the problem worse. I put this slide in here just to demonstrate how powerful cognitions about sleep can be. We often worry about sleep. I know I need to get rest for the next day. I know this is important for tomorrow, I have a huge presentation and I sit there and I stare at the clock.

Or on the right side of the slide, maybe we're in education and we've taught class all day. We're really tired because we didn't sleep the night before, and oh, my gosh, do I have to do this again tomorrow? We can build ourselves up to almost dread going to sleep if we haven't slept for several days.

(32:10): Forcing ourselves to try to sleep or dreading going to bed are counterproductive for sleep. These two pictures, I think, highlight those negative cognitions. You could even go a step further and say, "Well, I dare you to try to go to sleep right now." I dare you to do it, right now. Close your eyes. And I think Dr. Zhao, my colleague who's spoken on this before has actually offered bets to patients. I’ll give you $100 if you can fall asleep in the next minute". And so, that's hard it turns out. Forcing ourselves to sleep is contrary to what we're hoping to do. And so, in this type of therapeutic approach, we address those cognitions, we're honest with ourselves about the dread, the anticipation we might have around sleep.

(33:04) Components I talked about. So, I just want to highlight a couple. Certainly, getting the TV out of the bedroom, and using your phone less are not easy fixes but they're certainly effective. For some patients I've met with actually moving the phone from the nightstand across the room was enough, that was it.

(33:42): A consistent, regular bedtime and wake time can help with sleep problems. So, there's advantages to what I've mentioned before. But if you're really going to dive into trying to change your sleep schedule, I would argue that a regular wake time is critical, really critical. We're all guilty, at some point, of trying to catch up on sleep. After a long work week, you get to sleep in on Saturday, it's the only time you've got. Or you stay asleep six hours most of the week, you sleep 10 hours on the weekend. It can feel good. But in terms of helping your overall body adjust to that Monday night, when six hours are allowed for sleep, in the long run, it really sets you up for problems, knowing what your body needs.

(34:35): Avoiding daytime naps can improve nighttime sleep. I mentioned on the slide avoiding naps, That's within reason. Think about the impact naps have on your daily life, how tired you are when you wake up? Rolling back naps sometimes can really impact how tired you are at the end of the day. It's 9:00 P.M., things are winding down. 10:00 P.M., you lie down but you're still not really that tired. If you had napped earlier that day, that might be a target to roll back on.

I mentioned that I want to make interventions accessible to folks that psychologists have. The information's out there. But how many psychologists does it take to change light bulbs? You have to want to do this. It's challenging. Any behavior change is challenging. Things like obesity, diabetes, hypertension, these have very effective behavioral interventions associated with them. They're incredibly effective.

(35:45): Changing our behavior can be hard work but CBT-I can be effective if followed. Now, can folks do them? Not always. It's hard to change our own behavior. Sometimes I use the analogy of physical therapy. You could look up a lot of physical therapy exercises on YouTube. Now, can you do those regularly? Will you follow up with someone that will keep you accountable? Maybe. And it's worth having someone that's almost like a coach or helps you through some of these exercises so they really can be implemented in your life. That's the eventual goal.

So, acknowledge that it can be challenging. If you are motivated and you really want to dive into this, where would you go? This is quite hard work. There aren't a ton of folks that offer CBT for insomnia.

(36:45): Find a therapist who offers cognitive behavior therapy for insomnia. This is a map of those that are registered, which truth be told, I'm not registered as a licensed CBT for insomnia provider, so I'm not making it on this map, although I have extensive training in this area. So, this really highlights, though, that it's pretty challenging to find someone to walk you through this.

So, I've given you some tidbits around what you might consider implementing, some of the key components of CBT for insomnia. It may be that you have to branch out to behavioral health providers that have some training in this, could help you implement some of this, identify barriers, and not necessarily have to seek out an expert on this map because they're just few and far between.

(37:35): Apps are available for help with sleep problems. There are also several apps that are available. And I'm not endorsing any of these as scientifically superior to the others. But here are just a couple. You can see on the left that have been vetted scientifically and they all have some advantages, but also some disadvantages.

How much can you interact, continue to go back and interact with the app? How much feedback do they give you? There are certainly many apps out there that could guide you through this.

I don't have time to dive into this, but there are a lot of other types of insomnia treatments that have shown some promise. These are broad strokes. These are probably more effective for not actual diagnosable insomnia, but more sleep problems.

(38:32): Some other treatments can improve sleep quality but not necessarily help with actual insomnia. So, things like light therapy, melatonin, exercise have shown some promise in improving sleep quality. However, the jury's still out in terms of can they really be an effective insomnia treatment.

Also, I think many of these principles can be implemented without a professional. There are books out there, and the authors are not paying me to promote any of these materials, but there are several books out there that can walk you through how to implement these types of skills.

So, I hope this has been helpful in empowering you to at least think about sleep, to maybe put some practices into play in your own life that may improve your sleep quality. Bringing it up with your healthcare professionals is a good starting point. See if there are things that are realistic for you to implement and work with your team to improve your sleep and hopefully your health overall. So, with that, I'm happy to wrap up and take questions. Thanks so much.

Question and Answer Session

(39:48): [Marsha Seligman]:  Thank you Dr. Sannes for this excellent presentation. We will now begin the question-and-answer session. Our first question is, do you have any sleep statistics extrapolated for CAR-T patients and do they match your stem cell slide?

(40:17): [Dr. Timothy Sannes]:  That is a great, great question. I've seen some descriptive data, just talking about what we know of the problem. And I've seen similar sleep disturbances for patients that are undergoing CAR-T, so they have poor sleep in the hospital, higher sleep problems going into the treatment. Down the road, I've not really seen anything around [insomnia treatment for] CAR-T, but this is a newer type of therapy, so stay tuned. I suspect we'll see a similar pattern.

(41:02): All I've really seen, to date, has been around disturbed sleep leading up to it, and much worse sleep in the hospital. So, a really good question, I think there's more to come.

(41:15): [Marsha Seligman ]: The next question is how long should you try to fall asleep before leaving the bedroom?

(41:23): [Dr. Timothy Sannes]: Great question. The general timeframe is about 30 to 45 minutes. And so, a lot of people say, "Well, it takes me about 15 minutes to fall asleep." That's normal, what we would expect. It's when you get to that 45 minute, you get into an hour, you're watching the clock, that can become problematic over time.

It's something I work on with patients a lot. It is unique to individuals, but how you implement it is challenging. How often are you looking at the clock? Where's the clock? Having your phone on is not ideal because that typically sucks you into another world, thinking about other things. But can you turn the lights down on the clock? Is it not necessarily right next to your face?

So, the first thing you see when you look at when you haven't slept for some time is that number. And those little tweaks sometimes are things that we dive into when we do this type of treatment.

(42:39): [Marsha Seligman]: I have to take mirtazapine for my sleeping since transplant, 14 months now. Any side effects I should be concerned about?

(42:53): [Dr. Timothy Sannes]:  Great question. So, caveat, again, I'm not a prescribing physician, so I'm not writing for mirtazapine myself. And just for the audience, mirtazapine is also called Remeron. It's an antidepressant, but actually has beneficial effects for sleep and appetite, which are pretty common symptoms in cancer patients.

So, in the short term the data is clear that mirtazapine helps sleep. In the long term and addressing in true insomnia, it's not as clear. It doesn't seem to be quite as effective. So, that's one of those where , if you were to work with a sleep specialist, would get into the minutiae about how bad maybe sleep was before you started where and how it's improved.

So, is it falling asleep? At the beginning of the night, is it staying asleep throughout the night? Is early morning awakenings a problem? And that might be unique to your experience. But if it works, I mean I'm certainly not here to say, "Hey, roll back any medications you're currently taking." The difference is, I think with mirtazapine, is it's not the sleep aids that I was referencing before earlier in the presentation, which are hypnotics. And again, that's like Lunesta, Ambien, those kinds of things.

(44:25): [Marsha Seligman]:  What about sleeping over 10 hours? Is that an issue?

(44:31): [Dr. Timothy Sannes]:  Great question. So, oversleeping. So, if you remember there was one slide where I referenced a small subset of transplant survivors who have this hypersomnia, and that's what it sounds like may be going on.

But a few questions. Do you feel well rested when you wake up? If you only sleep eight hours, is it a completely different story? How's your quality of sleep throughout the night? When you wake up in the middle of the night, how long does it take you to fall back asleep? If you're lying in bed for an extended period of time within those 10 hours and not sleeping, that would be something that someone like me might target.

As I was suggesting on the earlier slides, we have a wide range of what each individual needs. It may be that your body actually needs more than seven hours. Tweaking that a little bit, you may find you have more energy through the day, you may have more restful sleep and you don't actually need those ten. But that would be something that you would have to work with someone closely on.

(45:41): [Marsha Seligman]: We have a few questions regarding using CBD oil, marijuana, melatonin, things like that. So, several people would like to know your thoughts about that.

(45:57): [Dr. Timothy Sannes]:  Certainly. Medical cannabis or CBD oil, that genre is, I feel, a bit of a cop out [in my answer].. People like me to say, "We don't know." But to be honest, that landscape is rapidly shifting. We researchers often can't keep up with the amount of use, or even modalities of use.

So, you mentioned oil, and that's important maybe in terms of how you use it. So you're not smoking it and maybe there's an advantage to that, but we have not done those studies. We don't know if edible preparations versus oil have a big difference. The main thing that cancer patients use cannabis for is pain. What we have seen is analyzing sleep quality as secondary outcomes in those pain studies. That's a roundabout way of saying it doesn't really seem over time, to be highly effective.

Initially it helped people fall asleep, but we also know that cannabis changes your sleep architecture, so how much REM sleep you get and how deep your sleep is. So over time, it doesn't seem that cannabis is a great treatment for insomnia, but I know that a lot of times it does help folks in the short term.

I think a lot of the more medical pharmacologic interventions that I was referencing are in the same boat. They can help folks initially, but if these sleep problems continue over months, over years, then that's where we really must come back to those behavioral treatments, breaking the cycle so to speak. Does that answer most of the questions I get? There's melatonin as well.

(48:10): [Marsha Seligman]:  Yes. Someone did ask about melatonin as well.

(48:14): [Dr. Timothy Sannes]:  Yes. Oftentimes that's medical interventions, pharmacologic intervention, that is tired first. A lot of people get benefits from melatonin. It's produced naturally by our body. It can reset the sleep wake cycle for some people.

What I was trying to highlight in my presentation is there is poor sleep quality, there's waking up tired, and then there's true insomnia. It may be that on the former, something like melatonin, something benign is actually enough to reset things. Many of my patients take melatonin and it does seem to help a lot of people.

(48:57): [Marsha Seligman]:  Does napping during the day or early evening affect your sleep for the night?

(49:04): [Dr. Timothy Sannes]:  So, the short answer is yes. We try to limit our naps. But what I was suggesting earlier is doing a sleep diary. So, at the beginning when I talked about treatments, I mentioned a sleep diary and I will always have folks document naps.

When I've done these in really great detail with patients, what do you know? There are many nights when they didn't sleep quite as well. It took them a while to fall asleep. They're waking up more. And on those days, they often had naps earlier in the day.

Now, I think the participant meant to ask about earlier in the day versus later in the day. Later in the day, closer to bedtime, there's a good chance that naps will be more impactful in harming your sleep quality. So, that is something that we try to roll back.

And at the same time, your body may be able to adjust to a brief nap. Do we take naps in bed? I usually say no. The one thing that is not well studied, but I've found sometimes can help, is making a nap more like meditation, an intentional 20-minute power nap thing. It doesn't work for everyone but getting in bed and hitting snooze 10 times with the covers over your head, that almost always sets someone up for a poor night’s sleep.

(50:33): [Marsha Seligman]:  Do you recommend Trazodone at night to help with sleep?

(50:39): [Dr. Timothy Sannes]:  So, again, not a medical recommendation, I don't write for it. But that's not in the class of the hypnotics I mentioned, so it doesn't have all those long-term poor health outcomes that I referenced. Trazodone [has the effect of] a tranquilizer and it does help a lot of folks sleep.

A lot of folks report a hangover the next day, for lack of a better term. And so, that's maybe in the class that I was mentioning around marijuana or cannabis where, , in the short term, it can help a lot of folks. Probably not the best for long-term use. Even though a lot of people do take it, it just truly knocks you out, and so we don't know a ton about what the long-term health effects are.

So, it's worth talking to your healthcare professionals about and maybe there's a balance between having some psychopharmacologic help like Trazodone, but then also trying to improve some of these behavioral aspects that could improve sleep quality over time.

(51:54): [Marsha Seligman]: Are there any foods or rituals that can improve sleep?

(52:01): [Dr. Timothy Sannes]:  Great question. So, I think I might focus my response on the word ritual, which is real. And actually, it is related to food because there's pretty clear data that if we eat within an hour before we go to sleep, it changes the blood glucose in our body. It may not feel activating, but there's more sugar, there's more physiological stuff happening if we eat half an hour before we go to bed. So, that's a ritual that I would dissuade you from doing, eating late.

In terms of a ritual, I do think that for some of the more mild sleep problems, making sure that you have some wind down time. And when I say that, people probably think, brushing their teeth, washing their face. I mean, having some ritual you do each night, whether it's reading a more relaxing book, or giving yourself a half an hour of no screen time before bed. Sounds easy to implement. I know it's difficult. But I have had folks that I've worked with where that and moving the phone off night table was enough.

So, ritual before around bedtime, I think, is a very good thing for your body and what it learns. If it wasn't clear from how I described our treatments, your body learning about what one does in bed is a huge driver of insomnia. So, certainly, rituals are important.

I'm certainly not a nutritionist. I'm not going to comment on what types of foods might or may or may not be helpful. I think just that word ritual is something to consider.

(53:55): [Marsha Seligman]:  Someone would like to know if you think that sleep patches are helpful.

(54:02): [Dr. Timothy Sannes]: Sleep patches. And the sleep patches include, well, I guess I'm not sure if you can interact with the individual asking a question. I'm not as familiar with sleep patches.

(54:18): [Marsha Seligman]: Well, the same person would like to know if what type of mattress is beneficial and the temperature in the room.

(54:29): [Dr. Timothy Sannes]: So, we're really getting into some specific recommendations, that's okay. My understanding is for sleep patches, these are typically melatonin. And so, the idea is that they would give it to your body in a more regular way throughout the night. So, there may be some benefits in that. I don't know the research around patches versus taking melatonin orally, but maybe there's some advantages there. And then, the next follow-up was around temperature in the room and types of beds?

That is very individual. Whether or not you're comfortable in your bed is pretty important. That's something that you'd work on with a behavioral sleep specialist. If you're shivering at night, certainly not an ideal sleep environment.

Typically, our bodies run hotter at night, which many of you may have experienced. And your partner, whomever you're sharing bed with, might have different requirements; they may run a little hotter than you. Those are the types of things that we sometimes tweak a little bit.

I'm not going to comment on the specific brands of bed or anything like that. But I think that is a very individual comfort level thing. Some people are side sleepers and they recommend softer beds for that. Some people sleep on their back and they recommend more stiff beds for that. And so, these are important nuances. It’s one size fits all recommendation.

(56:21): [Marsha Seligman]: We are running out of time, so this is going to have to be our last question. Someone would like to know what treatment is used for restless leg syndrome.

(56:32): [Dr. Timothy Sannes]:  Great question. And that is something that I did not spend a lot of time on. I'll try to make it brief. I group that in the same category as obstructive sleep apnea. You can get a sleep study where you actually go into a laboratory, do polysomnography. They hook you up to some machines and that type of medical assessment is important for restless leg or obstructive sleep apnea. And there are medications that can help with restless legs, and Gabapentin is one. And again, I'm not prescribing these but they certainly have efficacy in treating restless legs, which can greatly improve sleep quality.

(57:16): [Marsha Seligman]:  Closing. Thank you so much, that was so helpful. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Sannes 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. Enjoy the rest of the symposium.