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Doc, I'm Tired: New Approaches to Better Manage Fatigue and Sleepiness Associated With Common Medical Conditions

  • Authors: Chair: Joseph A. Lieberman III, MD, MPH; Faculty: Paul Doghramji, MD, FAAFP; Robert Malcolm, MD; Robert E. Rakel, MD
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Target Audience and Goal Statement

This program is designed for primary care physicians who see patients with a variety of medical conditions that commonly present with symptoms of persistent fatigue or daytime sleepiness.

Upon completion of this activity, participants should be able to enhance the quality of care and quality of life for patients in the primary care setting who present with signs of fatigue and sleepiness by:

  1. Describing the prevalence and impact of fatigue and sleepiness associated with a variety of medical, psychiatric, and sleep disorders.
  2. Recognizing the differences in the signs and symptoms of fatigue vs sleepiness.
  3. Identifying the underlying cause of fatigue or sleepiness.
  4. Evaluating available treatment options for persistent symptoms of fatigue or sleepiness after optimizing treatment of the underlying disorder.


It is the policy of the Center for Advanced Medical Education that all faculty participating in continuing medical education activities are expected to disclose to the program audience (1) any real or apparent conflict(s) of interest related to the content of their presentation and (2) discussions of unlabeled or unapproved uses of drugs or medical devices. For this educational activity we were asked to disclose any relevant information regarding relationships with commercial supporters. Faculty may have disclosed one or more of the following: grants/research support, consultant fees, speakers bureau, major stockholder, honoraria/expenses.

The material in this CME activity has been developed in accordance with the acceptable sources of scientific evidence.

This educational activity may include references to the use of products for indications not approved by the FDA. Opinions expressed with regard to unapproved uses of products are solely those of the faculty and are not endorsed by the Center for Advanced Medical Education, Cephalon, Inc., or any of the manufacturers of products mentioned herein. Faculty for this educational activity were asked to disclose any discussionof unlabeled or unapproved use of drugs or medical devices. Faculty disclosures are included in the course materials.


  • Paul Doghramji, MD, FAAFP

    Brookside Family Practice, Pottstown, PA


    Disclosure: Dr. Doghramji has disclosed that he he has no significant relationships with commercial supporters.

    Dr. Doghramji has disclosed that he intends to reference the unlabeled/unapproved use of modafinil for the treatment of patients with MS-related fatigue.

  • Joseph A. Lieberman III, MD, MPH

    Professor of Family Medicine, Jefferson Medical College, Philadelphia, PA


    Disclosure: Consultant: Abbott Laboratories Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Pharmaceuticals, Inc., Janssen Pharmaceutica Products, L.P., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi-Synthelabo Inc.

    Dr. Lieberman has disclosed that he intends to reference the unlabeled/unapproved use of modafinil for the treatment of patients with a variety of fatigue/sleepiness states/conditions. Dr. Lieberman will also discuss the unlabeled/unapproved use of SSRIs for the treatment of patients with anxiety disorders, and atypical antipsychotics to augment antidepressant therapy.

  • Robert Malcolm, MD

    Professor of Psychiatry and Family Medicine; Associate Dean for Continuing Medical Education, Medical University of South Carolina, Charleston, SC


    Disclosure: Grants/Research Support: GlaxoSmithKline, Sanofi-Synthelabo Inc.; Consultant: Bristol-Myers Squibb Company, Cephalon, Inc., Johnson & Johnson; Honoraria: Bristol-Myers Squibb, Cephalon, GlaxoSmithKline, Johnson & Johnson, Sanofi-Synthelabo.

    Dr. Malcolm has disclosed that he intends to reference the unlabeled/unapproved use of modafinil, pemoline, methylphenidate, amphetamine, and amantadine for the treatment of patients with OSA and narcolepsy.

  • Robert E. Rakel, MD

    Professor, Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX


    Disclosure: Dr. Rakel has disclosed that he has no significant relationships with commercial supporters.

    Dr. Rakel has disclosed that he intends to reference the unlabeled/unapproved use of modafinil for the treatment of patients with a variety of fatigue/sleepiness states/conditions. Dr. Rakel will also discuss the unlabeled/unapproved use of SSRIs for the treatment of anxiety disorders and atypical antipsychotics to audment antidepressant therapy.

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    For Physicians

  • This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). The Center for Advanced Medical Education, Inc. is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    The Center for Advanced Medical Education designates this educational activity for a maximum of 3.75 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

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Doc, I'm Tired: New Approaches to Better Manage Fatigue and Sleepiness Associated With Common Medical Conditions

Authors: Chair: Joseph A. Lieberman III, MD, MPH; Faculty: Paul Doghramji, MD, FAAFP; Robert Malcolm, MD; Robert E. Rakel, MDFaculty and Disclosures


Introduction and Program Overview, Presented by Joseph A. Lieberman III, MD, MPH

Fatigue vs Sleepiness

  • Managing fatigue and sleepiness is a tough topic because fatigue, tiredness, and lack of energy are among the most common symptoms we encounter in medical practice. On occasion, some patients will be so overwhelming that we feel defeated before we even start the process of trying to evaluate and treat them. Hopefully, by the conclusion of this program, we will all have a better understanding of what these conditions are, and more importantly, perhaps, a way to approach these patients so that we can optimize our time, the time we spend with our patients, and our therapy and treatment for them so that their outcomes are better. We have good evidence-based material that will help us do that. So that's the intent, to have us all feel better with this very, very common presenting problem of fatigue, or these common presenting problems of fatigue and sleepiness, or tiredness.

  • slide

    Slide 1.

    Introduction and Program Overview

    (Enlarge Slide)
  • Is this a patient you have seen lately? Is it sleep deprivation or chronic fatigue associated with another illness? Questions such as these pop into your mind. Sleep deprivation and chronic fatigue are not the same, and we will get into that differentiation as we go along. Then, what can I do to help this patient? This talk will help you answer that question.

  • slide

    Slide 2.

    Doc, I'm Tired. . .

    (Enlarge Slide)
  • Is it fatigue or is it sleepiness, because these are different. Both are universal symptoms associated with most acute and chronic illnesses. You see patients who are fatigued, certainly, with acute and chronic illness, and frequently sleepy. Fatigue and sleepiness also are associated with normal function in everyday life, and so when do you cross over into the pathologic range with these symptoms? We'll discuss that, too.

    Tiredness is one of the most common complaints of people seen in primary healthcare. How many of you have heard this? "I'm tired all the time." "I have no energy." "I'm not myself." "I'm always dragging." "I'm falling asleep at work." "I drove through a red light." The first two comments are kind of fatigue related; the last two comments sort of relate to sleepiness. We're beginning to differentiate between these 2 conditions.

  • slide

    Slide 3.

    Fatigue or Sleepiness?

    (Enlarge Slide)
  • Is it sleepiness or fatigue? Again, a common complaint associated with a variety of conditions has an impact on the physical, psychologic, social, and economic well being of your patient.

    Their impairment can be such that they are unable to make a living because they're falling asleep on the job, or they're so tired they can't get the job done. It isn't just the psychodynamic or the physical, it is also the socioeconomic issues associated with these conditions in their extreme state that are important.

    It does affect public health and safety. The person driving through a red light because he or she falls asleep at the wheel is a threat to public health and safety. There are many dimensions to this problem.

  • slide

    Slide 4.

    Sleepiness or Fatigue?

    (Enlarge Slide)
  • Let's get to some definitions, so that we're all working off of the same radar scope when we're dealing with these kinds of problems. Sleepiness is the state of decreased ability to maintain wakefulness or the increased propensity to fall asleep. That's what sleepiness is: the physiologic, when it's in a normal circadian rhythm, when it's a normal part of day-to-day existence.

    But excessive sleepiness, the second item, is a symptom of difficulty maintaining wakefulness and the increased propensity to fall asleep, even in inappropriate circumstances and in situations that interfere with activities of daily living. These are people who just go to sleep. They fall asleep at meetings; they fall asleep behind the wheel of a car, which is potentially catastrophic. It's not a good thing to fall asleep while you're undergoing your annual performance evaluation by your boss -- poor form to do that. So there are complications and implications of excessive sleepiness.

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    Slide 5.

    Sleepiness is. . .

    (Enlarge Slide)
  • What is fatigue, as differentiated from sleepiness? It's a state of sustained exhaustion and decreased capacity for physical and mental work that is not relieved by rest, at least not completely relieved by rest. These folks get up tired after a night's sleep. And they are tired all the time. Whether they are sleepy or not is immaterial; they are just tired. Whether or not they have had what would be a good night's sleep, they are still fatigued. That is, by definition, fatigue.

    It is subjective. There are no real tests for this with regard to traditional laboratory or imaging studies, but it's a subjective lack of physical and/or mental energy that interferes with usual and desired activities. That's what fatigue is, by definition: subjective.

  • slide

    Slide 6.

    Fatigue is. . .

    (Enlarge Slide)

Measurements and Studies

  • slide

    Slide 7.

    Epworth Sleepiness Scale (ESS)

    (Enlarge Slide)
  • Two scales used to measure sleepiness and fatigue are the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS). We will talk about these further momentarily.

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    Slide 8.

    Fatigue Severity Scale (FSS)

    (Enlarge Slide)
  • This is some general background information. This is a study done by Kroenke. Kroenke and colleagues looked at 1000 patients over a 3-year period of time in a very, very good medical setting. They evaluated these patients over that period of time, and at the end of the 3 years made a determination as to whether or not there was a biomedical explanation, in the traditional sense, for all of these presenting symptoms.

    It is kind of interesting, because as you can see, more often than not, there was no traditional organic reason found to describe, or to account for, these patients' symptoms. And yet, look at the incidence of fatigue in that study: it was second only to chest pain, as far as percentage of occurrence. The vast majority of these were not readily explained biomedically. So it's a very common problem, and it's one that frequently escapes traditional biomedical determination.

  • slide

    Slide 9.

    Percent of Internal Medicine Patients Reporting Physical Complaints Over a 3-Year Period

    (Enlarge Slide)
  • These are additional studies that looked at both the ESS and the FSS scores. This shows the normal range for the ESS, and the range of normal for the FSS. You can see that these conditions, like untreated depression, multiple sclerosis (MS), and seasonal affective disorder (SAD), all create abnormally high levels of fatigue and sleepiness in patients.

    Here, you can see the ESS scores, and you can see that these patients are also very sleepy. They didn't measure fatigue in these patients, they just measured sleepiness, but nonetheless, you can see that with obstructive sleep apnea and narcolepsy -- but not necessarily with schizophrenia -- these patients are sleepy.

  • slide

    Slide 10.

    Baseline Levels of Sleepiness and Fatigue

    (Enlarge Slide)
  • There is some overlap in conditions. This shows excessive daytime sleepiness, normal sleepiness, and as we saw in the previous slide, schizophrenic patients tend to have normal sleepiness, but it can, in some cases, leak over into the pathologic range of excessive daytime sleepiness, where narcolepsy is located. Then there's some overlap with Parkinson's, human immunodeficiency virus (HIV), and sleep apnea. These fatigue conditions give patients both excessive daytime sleepiness and fatigue. Chronic fatigue syndrome by definition is fatigue; major depression, however, carries with it a great component of fatigue, as does cancer. These patients are just tired. On occasion, they are very sleepy.

  • slide

    Slide 11.

    Overlap of Symptoms of Fatigue and Sleepiness

    (Enlarge Slide)

Impact of Fatigue and Sleepiness

  • What is the impact of chronic fatigue? In psychologic terms, people report decreased motivation, inability to concentrate, and poor memory. Half report feelings of sadness, frustration, and irritability. These are not necessarily nice people to be around.

    Socioeconomically, we see decreased social and family interaction and decreased productivity at work. These are people who are guilty of presenteeism, which means that they are at work, but they're not working very hard because they are incapable of doing that. They struggle with domestic and career demands because of their chronic fatigue.

  • slide

    Slide 12.

    Impact of Chronic Fatigue

    (Enlarge Slide)
  • Physically, patients report generalized weakness and limb heaviness. Sleep also is often unrefreshing for these folks, as we've indicated earlier.

  • slide

    Slide 13.

    Impact of Chronic Fatigue (continued)

    (Enlarge Slide)
  • What is excessive daytime sleepiness? It is the propensity to fall asleep in settings where one usually would not, or to fall asleep when one does not want to sleep. In most cases, it is pathophysiologic in origin.

    Psychologic or psychiatric conditions may be characterized by fatigue, weariness, and inactivity, but sleepiness rarely, if ever, has such an origin. In depression, you can see sleepiness and excessive sleepiness. But most of the psychiatric disorders don't carry with it this problem of excessive daytime sleepiness. It is more than likely some sleep problem that is related specifically to the sleep mechanism, and we will get into that in a bit.

  • slide

    Slide 14.

    What Is Excessive Daytime Sleepiness?

    (Enlarge Slide)
  • Of adults in the United States, 37% report that they are so sleepy that it interferes with their daily activities a few days per month or more. In addition, 16% percent experience this level of daytime sleepiness at least a few days a week or more. These folks are really sleepy.

  • slide

    Slide 15.

    Sleepiness in America

    (Enlarge Slide)
  • Why is this important? Cases of high-profile incidence, and we are all aware of these -- such as the Chernobyl nuclear reactor meltdown and the Exxon Valdez oil spill -- were results of sleepiness. The cost of sleep disorders or sleep deprivation is not really well established because again, it is one of those things that is hard to get your arms around. There is a lot of definitional difficulty with designing the studies. But if you need estimates, sleepiness is estimated to result in an impact of $15.9 billion in direct costs.

    Now that's sort of the Everett Dirksen model, with a million here, and a million there, and after a while, you're talking about real money. And that's the case here, because you could have $50 to $100 billion a year in indirect and related costs. That is an awful lot money, an awful drain on our productivity, and has a huge impact on our ability to compete internationally, and all those other kinds of things that are reflected in these numbers.

    As for motor vehicle accidents, falling asleep while driving is responsible for at least 100,000 crashes, 40,000 injuries, and 1550 deaths per year. We all know some incidence in our community where this has happened, with catastrophic results. People fall asleep at the wheel and run into school buses, and there are just all sorts of dreadful things that occur because people are sleepy.

  • slide

    Slide 16.

    Why Is Sleepiness Important?

    (Enlarge Slide)


  • When do you treat the symptoms of sleepiness and chronic fatigue? First of all, the cornerstone is identifying and optimizing treatment of any underlying conditions, because frequently, if you address those, then you don't have to worry about these other symptoms because they disappear. This is not always the case; we'll look into cases where this is not necessarily true. The first step is optimizing the treatment of the underlying condition to see if that relieves this particular symptom complex of either excessive sleepiness or chronic fatigue.

    You then treat the sleepiness or chronic fatigue if they persist after optimal therapy, they interfere with the patient's ability to carry out daily activities, or if the symptoms have a potentially negative impact on public health and safety. It's important to identify these folks and then treat them aggressively, because they could be putting your kids, my kids, our families, or our communities at risk just by virtue of what they do and are unable to do effectively because of excessive daytime sleepiness or chronic fatigue.

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    Slide 17.

    When Do You Treat Symptoms of Sleepiness and Chronic Fatigue?

    (Enlarge Slide)
  • This is a very brief overview of treatment options. We'll get into more detail as we go along, but the options are obviously nonpharmacologic and pharmacologic. Of the nonpharmacologic options, patient education and understanding normal sleep requirements are things that we need to do. Diet and nutrition have a role; exercise programs have a role. We will put them in context as we go through the process. Then, if you have to resort to it or you choose to use a pharmacologic approach, there are 3 specific classes of agents that are available: stimulants, wake-promoting agents, and in a unique case, anti-parkinsonian agents.

    The lack of approved products means no US Food and Drug Administration (FDA) indication for the treatment of fatigue and daytime sleepiness, which leads to off-label use of stimulants and wake-promoting medications.

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    Slide 18.

    Treatment Options: Overview

    (Enlarge Slide)
  • Let's just look at the schematic, which illustrates the way in which we are going to pursue the balance of this discussion with regard to the tired patient. The patient comes in, the assessment results in the determination that the patient is either fatigued, by the definitions we gave, or sleepy. If they're fatigued, you have to look at contributing medical or psychiatric conditions. If it is sleepiness, are they just getting inadequate sleep, which is endemic in our population, but nonetheless an explanation for why they're sleepy, or do they have a sleep disorder? Is this, for example, a patient who has restless leg syndrome? Is this a patient who has obstructive central mixed sleep apnea? We'll get into all those things as we go along.

  • slide

    Slide 19.

    Evaluation and Management of the Tired Patient

    (Enlarge Slide)
  • What we want to do then is to optimize treatment of the condition. Whether it's a medical condition, a psychiatric condition, an inadequate sleep situation, a social situation, or a sleep disorder, providing the optimal treatment is a first step in being able to deal with those particular issues.

    After you've optimized treatment of the underlying disorder, if there are persistent, residual symptoms, then there are the nonpharmacologic approaches: exercise, diet, and nutrition, as mentioned. And then there are the pharmacologic approaches, as we've indicated: stimulants, wake-promoting agents, and other drugs or treatments. This is the diagnostic algorithm that we follow.

  • slide

    Slide 20.

    Evaluation and Management of the Tired Patient (continued)

    (Enlarge Slide)


  • Let me recap, to set the stage for the following presentations. Is it fatigue or sleepiness? This is your first order of determination. Both are common. Both interfere with daily activities and quality of life. Both are manageable -- this is the important message. You can get your arms around these problems; you can manage these things. You just need to go through a stepwise process to do that, which we will lay out for you.

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    Slide 21.

    The Tired Patient: Recap

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