2014 Learning Conference
Hilton Americas Hotel § Houston, Texas § July 10–12 This transcription of Dr. Alan Pocinki’s “Breaking the Cycle of Chronic Pain, Poor Sleep, Depression, and Fatigue” was provided by Christina Cole. Many thanks for her gracious help in doing the work! The video of Dr. Pocinki’s session is available on the EDNF YouTube channel, http://bit.ly/EDNFYouTube, or directly at http://youtu. be/9TxKDVkaDFM
"For most people pain is probably their primary driver behind depression, fatigue and poor sleep. These things are inter related. If you are depressed you are going to be more sensitive to pain, your sleep is going to be bad, your fatigue is going to be bad; as long as you're in pain it's going to be hard to get your depression under control, it's going to be hard to get restful sleep and your fatigue is not going to improve. How do you break this cycle?
I rarely include references in my slides because a lot of what I say, up until recently, has not been supported by any medical literature so I'd echo what Clair said, it's nice to start finding some things. This, I just came across literally on the plane yesterday, viewing some abstracts
from last year's (2013) Myopain conference. It's a big international conference on pain management and Dr. Mease was the coordinator of the program, and he got up to make introductory remarks and said: "Every patient with chronic widespread pain requires evaluation of their sleep, since poor sleep and depression are independently associated with pain." This is just huge because pain specialists don't know anything about sleep, so for a pain specialist to get up at a pain conference and say "pain patients need to have their sleep looked into," is pretty ground-breaking.
So how do you break the cycle? The basic approach is you have to address everything together. As I said: as long as you're in pain your sleep/depression/ fatigue are not going to get completely better; as long as you're depressed, pain/sleep/fatigue will not improve much. The big hurdle, the big obstacle here is there is no magic formula, no magic pill that will work for everybody. Everybody is different. We can go around the room, and as you've seen in some of the surveys that Clair presented, 60% of people will have this, and 40% of people will have that.
No two patients are going to be the same in terms of their symptoms. There is tremendous variability in how people respond to their symptoms; two patients with identical medical problems can have different sensations and reactions to them depending on their life situations, their support systems, and whether or not they tend to be a generally optimistic or pessimistic person. Then there are physiological factors. A big one is how healthy were you before things started to fall apart? Do you have other medical conditions unrelated to EhlersDanlos that are going to complicate matters? I'd like to put in a plug for the Genelex people because pharmacogenetics is really a big factor. Individuals respond differently to medications and understanding what their pharmacogenetic background is takes a significant amount of trial and error and the guesswork out of coming up with medications.
Every patient requires a comprehensive treatment program that's also going to be individualized to their particular situation. How do we go about addressing pain/depression/fatigue/poor sleep? Clair eluded to this one study on pain, the different types of pain, and so figuring out what kind of pain somebody has is pretty essential in deciding what's going to be the optimal treatment for them. Muscle and joint pain tends to be primarily mechanical in this condition but there are inflammatory components, there are some neuropathic components. Visceral pain, means pain typically in Ehlers-Danlos, is going to be abdominal pain coming from the internal organs and that can have inflammatory/mechanical/neuropathic and even occasionally ischemic, being lack of blood flow causing pain. I could easily talk for an hour about headaches, 15 or 16 different types of headaches that patients with Ehlers-Danlos are predisposed to. It's certainly not a question of "Oh you have headaches, here take this pill or here do this." A lot of patients and doctors themselves are discouraged, they'll treat somebody's headache and maybe the
headaches get 60% better, and that's because you've only treated one type of headache and there are still other types of headaches that persist.
The biggest issue in approaching pain is don't underestimate it. This is a major problem for patients, this is a major problem for parents and it goes without saying unfortunately for physicians too. It's hard, especially for young people, to recognize how much pain they're in. We have this unfortunate system of asking patients to rate their pain on a scale from 0-10. If you've been in pain for much of your life, you don't know what zero feels like, so it's really hard to tell where you are. Conversely there are lots of patients who recognize they're in pain, but say things like "Oh it's not that bad, I'm used to it, I've learned to live with it, I don't really want to be taking lots of pain medications." That's not helpful. Living in pain is perpetuating the vicious cycle of poor sleep, fatigue, and depression.
How do we address depression? Depression is different things for different people. I find in this construct, to be useful, a pharmacological approach when you get to the point that depression is bad enough and a big enough factor in pain, sleep, and fatigue to warrant medication for it. This is not 100% scientifically and pathophysiologically accurate, this is a construct that I modified from a pamphlet many years ago that patients have found very helpful in understanding why, for example, a particular medication might relieve some of their symptoms of depression but not all of them. So you'll see that a lot of physicians reach first for serotonin drugs in treating depression. Serotonin drugs are great for anxiety, worry, and obsessive compulsive tendencies, but they really don't do much for pain, fatigue, cognitive impairment and motivation, which tend to be pretty widespread features of depression in patients with Ehlers-Danlos Syndrome. Depression, like pain, tends to be something that patients under estimate. They say "Well of course I'm depressed, wouldn't you be depressed? My quality of life is terrible, I'm in pain and I can't do the things my friends do. It's normal and understandable for me to be depressed." That's very true, but it doesn't mean that it isn't worthy of being addressed in some way.
Like pain, saying that "I am depressed and I am used to being depressed ,it's not that bad I can deal with it. I don't need to take medications and I don't need counseling, I can just suck it up and deal with it" is not a helpful approach to getting better.
A couple of points to highlight. You don't have to be sad to be depressed. Again to go back to that Venn-diagram; you can have problems with fatigue, poor concentration, and lack of motivation and not be crying or sad all the time and still be depressed. Similarly, the concept that deficiencies of these various neurotransmitters shown in the diagram can be significant even in the absence of what are generally considered the diagnostic features of clinical depression.
Sleep, again very much like pain and depression, requires different types of approaches for different types of sleep problems. Some people will primarily have problems getting to sleep, others will have trouble staying asleep and others will get to sleep ok but will wake up and can't get back to sleep. There are many factors that affect this: pain, anxiety, worry, and environmental factors can't be overlooked (ex: getting a new mattress and pain/sleep becomes better).
Again, the theme here: don't underestimate how bad your pain is, don't underestimate how depressed you are, don't underestimate how bad your sleep is. I hear over and over, I ask
people how they are sleeping and they will say "fine" or "I don't really sleep that well and I never have so I'm used to it and I've just never been a good sleeper." Again, you can't really expect your fatigue, pain and depression to get better if you're not getting a restful night's sleep. The big problem with sleep is that a lot of people do not sleep well and aren't even aware of it, that's the concept of "sleep misperception." Very often I hear from people "I'm a great sleeper. I can sleep anytime, anywhere, 10, 12, 14 hours. I have always been a good sleeper." When I say to them "I think that means you're not a good sleeper" they're really having trouble getting their minds around that concept. If you sleep 9 hours and you wake up tired, something's wrong with your sleep. They say "no, I sleep fine." Well you just said you slept 8 or 9 hours and you wake up tired, or you sleep 8 hours and a couple hours later you'll lie down and have a nap. I hesitate to tell people that's not normal, because normal is so different for different people when trying to explain this or asking a patient "do you feel rested when you get up in the morning?"
This idea of sleep misperception is actually not unique to Ehlers-Danlos in the concept of nonrestorative sleep; there are studies showing as many as 90% of patients with sleep apnea are not aware that they have it because they're asleep. A lot of patients with periodic limb movements can be moving around and thrashing all night and not be aware of it. The most common features of non-restorative or poor quality sleep in Ehlers-Danlos tend to be a lack of deep sleep and frequent disruptions of continuity of sleep, which we call arousals. The only real symptoms of those are feeling tired when you get up in the morning. It's not anything else you're going to be aware of. Because of this, sleep studies are really helpful; we really just don't know what's going while you're asleep without the sleep study. The problem is that most sleep specialists are not trained to recognize the type of sleep disorder we see most often in Ehlers-
Danlos patients, and so I see a lot of patients come in with reportedly normal sleep studies that are clearly not normal.
Home sleep monitoring is really helpful because it often can be difficult to sleep in a sleep lab; unfortunately the best of the home sleep monitors, the company went bankrupt about a year ago, so we're limited in what's available now. One of the most helpful things we have now are the movement based monitors: Fit Bit, Jawbone, and Basis; things that can tell you a little bit about when you're asleep and when you're awake, but not all the sleep stage information that we'd like to have.
As I mentioned, the most common sleep disorder we see in Ehlers-Danlos patients is characterized by frequent arousals, which are these disruptions to the continuity of sleep and awakenings. In the sleep lab we define awakening as a disruption of the continuity of your sleep that lasts more than 30 seconds, turns out that most people need to be awake for at least 2 minutes to remember having been awake. If your sleep is disrupted for less than 30 seconds, we call that an arousal. In this first horizontal bar, these are what we call "hypnograms", showing sleep stages through the course of the night. You'll see that this patient starts off in green, which is shallow sleep, then there's a big chunk of blue, which is deep sleep, then shallow, then the reddish-brown is REM, then the patient cycles through mostly shallow sleep and REM for the rest of the night, with most of the deep sleep being early in the night. The lower bar is a fairly typical sleep study for a patient with Ehlers-Danlos who slept for 7 hours and thought she slept pretty well and woke up feeling like she hadn't slept. You'll see right away by looking at this that there is no red and no blue. She has no deep sleep, essentially no REM, nothing that looks like a normal cycle. What you can't see here, is that she remembered waking up twice and she actually woke up 23 times. In addition to the 23 awakenings, she had 125 arousals. So the continuity of her sleep was broken 150 times in 7 hours and she was only aware of 2 of them, so that is why you really need a sleep study to find this.
I always add this slide because the unfortunate footnote to the previous slide is that the second sleep study with 150 arousals was read as "normal" by a board certified sleep doctor. So, although the doctor here is telling the patient here that his MRI shows his head is riddled with conventional wisdom, it should in fact be the patient that is telling the doctor that his head is riddled with conventional wisdom.
Fatigue, like pain, depression and sleep, different types of fatigue and different causes of fatigue need to be addressed differently. Clearly much of the fatigue in Ehlers-Danlos comes from poor sleep, chronic pain, depression and autonomic dysfunction; but that doesn't mean these are the only causes of fatigue and as Clair eluded too, as many contributing factors that you can identify and address and do something about are going to help, even if they're only small pieces of the puzzle.
I don't have time here, in past years I've spent an hour just discussing autonomic dysfunction. I don't have time to go into that, but since so many of you have never heard me speak and I think there's a talk on POTS, autonomic dysfunction affects so many other things. Very basic 2 minutes on the autonomic nervous system: basically, for those of you for whom this is a new concept, the autonomic nervous system regulates everything in your body that goes on automatically. So, blood pressure, circulation, breathing, digestion, everything that's happening all the time that you don't have to consciously think about. It's a pretty simple system. The sympathetic side generally speeds things up and can be thought of as an accelerator and that's your "fight or flight" response. The parasympathetic system is "rest and digest" and can be thought of as the brake. Sympathetic hyperactivity, or the tendency to make too much adrenaline in response to minor stresses can, I think you can imagine, make pain sensitivity worse, can make sleep problems worse, and at times can mimic anxiety, panic, and even hypomania- that's something I spoke for almost an hour about last year. If your parasympathetic nervous system is over active, as Clair mentions is less common, that can aggravate fatigue and a general sense of malaise.
In addition to the big three of pain, sleep, and depression, anemia is a fairly common problem. We always look for low thyroid and other common, routine medical problems need to be looked for. Micronutrient deficiencies are very common in Ehlers-Danlos. The two big ones are probably vitamin D and B-12 deficiencies, remarkably common in the population in general, but seemingly more prevalent in Ehlers-Danlos patients as well. Magnesium deficiency is also very common in the general population. The problem with magnesium deficiency is that standard blood test for magnesium is not going to tell you where your magnesium levels are because only about 1% of your total body magnesium is in your bloodstream. For a lot of different symptoms we will empirically give people magnesium, it relieves fatigue and muscle cramps
and helps with digestion. Don't overlook simple things. Hormone deficiency is something I think we are just starting to look at and find, frankly we are having trouble finding endocrinologists to help us sort out this part of the puzzle. Within the past year I've looked at and been struck by the low levels of DHEA and testosterone, especially in young women. I started looking because I was seeing young women who were feeling better, sleeping better, having more energy, exercising regularly and despite regular exercise were not building any muscle tone, not building the strength and muscle tone they needed to stabilize their loose joints and it was clear that something was missing. An extremely high percentage of these women turned out to have abnormal testosterone. Normal testosterone is between 15 and 75, about 80% of these women were in the single digits, with levels like 4 or 6. Salt/fluid imbalance is another thing we talk about. Those of you with orthostatic intolerance or POTS or just generally feeling light headed have probably been told to increase your salt intake. For 20+ years we've told people "eat more salt, drink more water" and this is very surprising to me in the past year, when I went to look at the salt/fluid imbalance to see whether my patients were doing this appropriately on their own and I was struck by the fact they're not and I will show you those data in a second. I just added mitochondrial disorders which are not common but if you're really getting to the bottom of the barrel and nobody can understand the basis of your symptoms, you might read about mitochondrial disorders.
Again, for want of finding somebody with more expertise to help me understand this, I readily admit I don't know a lot about kidney physiology and things like that. I thought I could at least look at the concentration of the blood and the concentration of the urine to get some idea of what's going on with somebody's salt/fluid balance. What I've found is that total concentration of everything in the blood should be between 280 and 300, and over and over again I was
seeing numbers right at 280, 281, 279, 277, and these were patients who had been told "eat lots of salt," and yet still their blood concentrations were low. If I looked at their urine to see ok, is this a problem with the kidneys? Are the kidneys dumping salt and fluid? The patient is eating plenty of salt, are the kidneys, for some reason, not holding on to it? Turns out that is not the fact. The kidneys are trying to hold onto salt and get rid of plain water to try and get the concentration of the blood up. The bottom line is, 80-90% of people that I've been seeing that have been told "eat lots of salt, drink plenty of water" are getting way too much water and not nearly enough salt.
The best "solution," no pun intended, are the electrolyte drinks. Basically, when you drink plain water you are diluting your blood and then your kidneys have to work hard to hold onto salt and get rid of the water you just drank to keep your blood concentration up. Replacing plain water with an electrolyte solution is an easy way to go. Limiting the amount of plain water you drink is helpful. Forget the conventional wisdom that salt is bad for you. More striking than almost anything recently has been the number of times I have asked people to estimate how much water they drink in a typical day and they say "Well, I don't really know," and I'd say "Ok, do you drink water in this (water bottle)" and they'd say "Yea, I probably drink 10 or 12 of these in a day." You're drinking 5 or 6 liters of water day, there's no way you can get enough salt to keep up with that! Again, looking at non-pharmacologic stuff as much as possible, trying to improve salt/fluid balance has made a big difference in a lot of patients. The question is, can you get electrolyte replacement without sugar? Yes, there are a few such products, one that I recommend is called Nuun. They are little tablets, you drop one tablet into your standard water bottle and provides an instant electrolyte solution, so it's certainly convenient. PowerAde Zero is sugar-free electrolyte supplement. Again, I am just starting to learn about these things, you want to look at the sodium concentration. A lot of the sports drinks will have sodium
concentrations between 150 and 300 mg of sodium per liter, Nuun is about 720. The bottom line here is that people that are being told to eat a lot of salt and drink a lot of water, aren't getting nearly enough salt. (Other electrolyte solutions mentioned: Skratch, E-lyte, Selectrolytes) *Question about daily IV saline infusions: What I've found is that most people, even patients who were at one point getting IV saline, most people don't need it. Most people can regulate their salt/fluid balance orally. The problem with a lot of people needing IV saline is that they were drinking too much water, and you need salt to hold onto water. Trying to explain to people that you're chronically dehydrated because you're drinking too much water is not an easy thing to do! If you think about it, you need salt to hold onto fluid and you think about this concept that drinking water dilutes out your blood and then you have to get rid of the water in order to keep your blood balanced, drinking plain water often can make your problem worse.
How do we break the cycle? Clearly we need to go and identify as many treatable and correctable factors as we can and put together a comprehensive treatment program. Here is where I am going to skip a lot of specifics. The one thing I'm going to stress on this slide is to have some realistic goals. Pain relief, reducing your pain levels by 50% is a realistic goal. Taking someone whose pain is a 6 to 8 and taking it down to a 1 to 2 may not be a realistic goal. Remember, this is both a challenge and a help in some ways, I often tell people my job would be a lot easier if all the parts weren't connected. One treatment can often make something else worse or something else better, or one medication may counteract the effects of another. Ideally we try to use that to our benefit and use a medication that, for example, might help both pain and sleep.
This is another construct, another way of looking at this vicious cycle that a lot of my patients find very helpful, that is to say "Ok, what do I have to do to get better?" If you look at fatigue as the central problem with depression, pain, and poor sleep all contributing to fatigue. What I suggest to people is think about having your own fuel tank, your own energy supply, and sleep is you best chance to put gas in your tank. Stresses like pain suck up energy. Chronic dehydration is depleting energy. If you're tired but constantly trying to plow through the fatigue, that is using up energy. Any sort of emotional stress or depression will use up energy. Any other metabolic factors, deficiencies of vitamins, and things like that are using up energy. If you're also trying to exert energy to deal with household responsibilities or school/ work, all of these things are drawing from your energy supply. Then it becomes easy for my patients to look at this and recognize that on most days they're using up more energy than went into the tank the night before. This is really how the vicious cycle spirals out of control. The answer to "how do I get better?" is to try and undo this. Get a better, more restful night's sleep, reduce your pain, rest when you're tired, don't plow through the fatigue. Make sure that you are not dehydrated, that you are regulating your salt/fluid balance. Recognize the other stresses that are using up energy and try to minimize them as best as you can.
I would like to stress that putting together a treatment program is not all about medication. Basic things like resting when you're tired and not forcing yourself to keep going any way, are important measures. There are lots non-pharmacologic approaches for the treatment of pain, depression, sleep, and fatigue. I will go through those very briefly.
Clearly, exercise and physical therapy are helpful long-term if you're getting the appropriate physical therapy of course. Massage can be tricky, if it's either too aggressive it can be painful, if it's too relaxing it can further destabilize your joints. Some people find things like acupuncture and dry-needling to be helpful.
Pain medications, again I'm not going to go through this list. Despite the busy slide, it's actually a fairly short list. When you're dealing with pain, you'll find you can work down the list pretty quickly trying things that don't help or you have side-effects from them and have to move on to something else.
Similarly there are a lot of non-pharmacologic measures to deal with depression, anxiety, and stress. In general I find that the idea of empowerment, the idea of having a treatment program, and saying "here is what I need to do to get better," helps people have a more positive outlook and that's very important in their recovery. Trying to reduce stress and recognizing that various stresses whether they're emotional or physical are sucking up the energy that you're trying to conserve. Relaxation techniques are very helpful, especially in the setting of autonomic problems where your body is tending to over react to stress, if you can tone that down with things like deep breathing or meditation, a lot of people find those things helpful. There are
other interventions where you need a specialist to help you; things like neurofeedback, mindfulness based stress reduction, and more conventional counseling/psychotherapy.
I'm going to come back to this in terms of choosing medications. If you look at what your primary symptoms of depression are that's helpful in saying different medications work through different pathways. As I mentioned, the serotonin drugs will help mostly with things like anxiety, worry, and obsessions. The serotonin/norepinephrine drugs can help both those and pain/fatigue. Wellbutrin can help a lot with energy and motivation. Remeron is an interesting drug that can help with sleep and appetite as well as mood. A lot of patients will take an antidepressant and feel somewhat, but not completely better. Adding a so-called augmenting or secondary agent can help boost mood, energy and sense of well-being. I added here specifically that benzodiazepines like Valium, Xanax, Ativan, and Klonopin are NOT medications for depression. I see them prescribed a lot and these are "downers," they make depression worse! When I see people on Klonopin (Clonazepam) in particular, I will say to them "You are
complaining about cognitive problems, fatigue, and depression. Why are you taking a medication that causes all three of those things?"
Of course, there's a lot of non-pharmacologic measures to improve your sleep. Basic good sleep hygiene, comfortable mattress, making the room dark and quiet and a comfortable temperature are really important because your body has trouble with autonomics and regulating things. Your body is going to over respond to small noises, it's going to over respond to light. Look for sleep apnea and treat it if it's significant, but be wary that a lot of sleep doctors will find very mild sleep apnea on a sleep study and because they don't have a better explanation for what's wrong with your sleep they'll recommend that you be treated for sleep apnea.
Medications for poor sleep- this again, I think I gave an hour lecture on this. It's very much trial and error and most patients are going to need a combination of medicines with complimentary effects. One thing I will point out here, a lot of people do not think about taking pain medication at bedtime. They are just not aware of the fact that they are in pain overnight and how much pain may be disrupting sleep. Finding the right combination can be a frustrating trial and error process; frustrating for the doctors as well as the patient, but when you do find a combination that gets you a restful night's sleep that really gets the whole ball rolling, it gets the whole vicious cycle going back the other way.
Again, I don't have time to go through all of these various different medications we use to help improve the quality of sleep in various different ways and addressing different problems people have with their sleep.
Measures overall to reduce fatigue- the biggest one seems obvious, again I keep coming back to getting adequate rest. There are so many of us that are so busy and try to pretend we're not sick and plow through the day and keep doing all the things we have to do. If you can, just taking short breaks, even a 5 minute time-out, put your feet up, close your eyes, let your motor cool off for a minute and you won't be quite as wiped out at the end of the day. Exercise, however limited, is going to be important. I saw several people yesterday in the mini consultations that were either too exhausted or in too much pain to exercise. Almost everybody in those situations can at the very least start by lying flat on their back, closing their eyes, and moving their arms and legs around a little bit without having to worry about gravity or aggravating pain. Stimulants can be helpful, they're sort of a double-edged sword. You really have to be careful that you're not taking stimulants to help you plow through the fatigue. If you're exhausted from pain and poor sleep, you need to deal with those things and not just take stimulants. Stimulants can aggravate autonomic dysfunction, you could buzz along on your stimulant, but when your stimulant wears off you will crash and that's just aggravating the whole vicious cycle that we're trying to correct. On the same token, judicious use of stimulants early in the day can help reset your circadian rhythm. If you are somebody who can't get up early and it takes you hours and hours to get functional, then you are going to have trouble getting to bed at a reasonable hour. If you can get up and take something to help you be a little more active early in the day that can often help with your sleep and your circadian clock. Nutrient supplements can help with fatigue, especially B12. Treatments to improve your circulation and autonomic function; we talked a lot about adequate salt and fluid, some patients will need medications as well.
How do we break this nasty, vicious cycle? We look at each one of the contributing factors and we try to identify the ones that we can do something about and put them together into an overall comprehensive treatment program. *Question about circadian rhythm dysfunction: in Ehlers-Danlos it's very prevalent for people to have circadian rhythm disorders. The most common pattern are patients who drag through most of the day and either get a little energy in the morning that fades by late afternoon/early evening and then get a second wind between 9 and 10 o'clock at night and will say "midnight is the most awake I am all day, so there's no way I can go to sleep then." That's very common and for some people, unfortunately that's their first wind and they drag through the whole day and are not awake until 10 o'clock at night. That type of circadian problem is very prevalent in Ehlers-Danlos and I don't know enough about it to guess what the underlying pathophysiology is. *Question: would medications that help to reset circadian rhythms help with other symptoms? Yes, we often will try to do that.
We are coming back to this slide and the overall going through piece by piece. What can we do to relieve pain as much as possible, how can we optimize sleep quality, how can we minimize dehydration, reduce other stresses in order to conserve energy. As you replenish your energy pool, you'll get the vicious cycle going back the other way with less pain, a more restful night's sleep, you'll have more energy. You'll do more; the more you do, the better you sleep. The more you sleep, the better you feel and your mood gets better while your energy level improves. As your depression gets better, your pain/fatigue/sleep will get better. As your sleep gets better, depression/fatigue/pain are reduced. As your fatigue improves, then you feel better and do more and conversely you feel better and your mood improves. This whole vicious cycle is reversed, and that's how you get better!"
Dr. Pocinki's Acknowledgements:
Transcribed by Christina Cole 8/11/14 c.cole617@gmail.com