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Sleeping with the Enemy: Treatment of Fatigue in Individuals with Cancer

Massachusetts General Hospital for Children, Boston, Massachusetts, USA and Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Robert H. Wharton, M.D., Spaulding Rehabilitation Hospital, 125 Nashua Street, Boston, Massachusetts 02114, USA. Telephone: 617-573-2637; Fax: 617-573-2209; e-mail: Robert_Wharton{at}hms.harvard.edu

Key Words. Cancer • Fatigue • Psychostimulants

	INTRODUCTION

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
For people with cancer, like me, cancer is the C word. What I have discovered is that cancer does not travel alone, but is accompanied by its insidious colleague, namely fatigue, which, for me, is the F word. This profane side effect adds additional disabling restrictions to my struggle against cancer. An important warning for many, but a life-limiting condition for others and me with cancer, how can fatigue both defend our well-being and disable our desires? What parts of our body control our sense of fatigue? Can we achieve control over its working parts?

How many times have I heard that a particular therapeutic agent or combination of agents will have side effects, perhaps nausea, bowel irritation, anemia causing tiredness, and of course, fatigue? I have been generally informed that some degree of fatigue is inevitable and needs to be endured. I was told by my oncologist and radiation therapists that my energy resources will be limited, I will neither feel like nor be able to work, will not seek social interactions and activities with my family and friends as I had before my diagnosis, and that treating any underlying purely physiological source of the problem, epoetin alfa (Epogen^®; Amgen; Thousand Oaks, CA) for anemia, for example, while important, will not fully restore my energy resources to precancer levels. Further, I was told I needed to accept fatigue's presence for the duration of my battle against cancer. I was admonished to passively accept its intrusive and disabling affects, as though passive acceptance of any part of having cancer could be acceptable.

While I often learned to adapt to certain physical and other restrictions resulting from my diagnosis, I needed to not permit cancer to curtail all vestiges of my potential resilience. There may not be medical weapons that will sufficiently defend the integrity of my bodily organs, but perhaps there are untried resources to better mobilize my emotional energies so I can again vigorously pursue my life's goals.

	WHY TREAT FATIGUE?

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
The triple threat of treatment—chemotherapy, radiation, and surgery—as well as cancer itself, can independently and, in an unfortunate coalition, result in fatigue. However, medical problems must first be evaluated and either discarded or fully treated before settling on the orchestrated triad, seeking to attack the ubiquitous enemy. This many-weaponed army, seeking to kill in self-defense, becomes a metaphor for the uniform, which encases its own actions—army fatigues.

Fatigue affects my quality of life, my ability to not yield to despair and depression, and to continue to live a life of meaning. In his book Man's Search for Meaning, Viktor E. Frankel, writing about his suffering in Nazi concentration camps, found that those who were able to hold onto meaning, perhaps reuniting with a child who had been put in hiding, completing some special project, or fulfilling a particular goal, were better able to fight off despair, better able to find a reason to go on [1].

Fatigue restricts my reaching far enough into myself for the innate resources I know I possess to fight to my potential and care for myself and others. Fatigue bars access to my spiritual, religious, and family support system, the essentials of who I am. Fatigue also affects my ability to mobilize my energy to fight my disease. In addition, fatigue prevents me from developing new additional resources at a time when they are most needed. As my cancer attacks with no such self-imposed restrictions, never seems to tire from its mission, uses all the weapons it can, at times even succeeding in turning some of my weapons against me, has no moral quandaries about the destruction it causes, and, in general, seeks my annihilation, shouldn’t I try to equip my defensive forces with all my available tools as well?

Fatigue also compromises my connections to my crucial external support systems. For me, and I would assume many other individuals, fatigue restricts the opportunities to actively participate in interactions with my family, have more productive time for myself, work more efficiently when I chose, enjoy ball games, movies, museums, share with friends, make love, refurbish a turn of the century child's desk, take photographs, listen to music, and walk through the woods. For children, fatigue restricts their energy to play with other children, share games and pleasures with their siblings and parents, play Nintendo, listen to music, burn CDs, communicate with friends on the Internet, play an instrument, go to school, or participate effectively in home schooling.

For we adults, talking with, engaging in, or perhaps modifying our typical precancer activities with our children, spouses, partners, other relatives, and friends, and even building new networks of supportive friends; continuing to engage in activities that had brought us feelings of self-worth and comfort, whether these fulfilling activities are our work, hobby, family, or maintenance of a social network; or starting a project we contemplated but believed we never had the time for, are all efforts that could be vigorously pursued.

	MEDICAL CONDITIONS CAUSING FATIGUE

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
When my fatigue started, my oncologist educated me about medical conditions that cause fatigue in individuals with cancer. Anemia was first and foremost. Certain chemotherapeutic agents, leukemias, invasive bone marrow tumors, and some renal disorders lower a person's red blood cell count, ultimately leading to anemia, the most prevalent, and generally treatable, cause of cancer-related fatigue. Epoetin alfa provided the necessary adjustment to restore my hematocrit to a normal range. I clearly felt less tired and had more stamina. However, unlike the mechanical adjustment to my red blood cell quantity, this energy correction, while important, felt incomplete. I learned that having a low red cell count was not the sole or even the principal source of my fatigue. In addition epoetin alfa's effects were transient. My chemo and epoetin alfa, like enthusiastic, uninhibited, and impatient siblings engaged in an irritating tug-of-war with the Nintendo controls, would continue to be combatants until a higher authority took charge.

My oncologist next mentioned hypothyroidism, resulting from head and neck radiation, as a potential cause of my fatigue, since my head received considerable radiation and my thyroid was peripherally in the radiation field to my chest. He checked and found that the gland had not succumbed to the chaos swirling above and below it. It was still receiving, manufacturing, and dispensing its products with unblemished efficiency. Neither chemo, radiation, nor the tumor itself could keep it from its appointed task. Its mail was being delivered.

As my kidneys were cancer free, my oncologist wasn’t concerned about my renal function, and therefore, knew that I could not have anemia from renal failure itself nor, he taught me, from hypercalcemia that may result from advanced disease. Finally, he assured me, my fatigue did not indicate that I had advanced disease, the time when my ability to mount a credible offensive, or even find a cave to hide in, had not yet arrived.

At one appointment, being a comprehensive physician, my oncologist asked me about depression. I told him that after the surgeon who performed my biopsy told me I had cancer, my wife and I hugged and shared several tearful moments. I then went to my medicine cabinet, knowing that becoming depressed would interfere with my upcoming fight against cancer, and restarted an antidepressant medication that had been effective during an earlier challenging time in my life. In retrospect, this had been a critically important action. Though neither my wife nor I believed I was currently clinically depressed, we nevertheless agreed to increase my antidepressant.

Over time, my oncologist continued to identify other occasional causes of fatigue. He would check my various medications, especially pain medications, to ensure they were not responsible for, or at least contributing to, fatigue. Medication sufficient to effectively treat esophageal pain caused some mild but not disabling fatigue. He also carefully reviewed my sleep pattern, exploring whether pain, depression, or medications, all amenable to some treatments, were responsible. He prescribed a stronger antireflux medication to diminish my occasional night wakening. We even reviewed whether inadequate or excessive heat, environmental allergies, neighborhood noises, or the random, unrestricted movements of my two dogs—excuse me but you’re standing on my nose!—provided enough of an irritant to disable my natural triggering signals that had previously affected my generally smooth transition from an awake to a sleep state.

My oncologist then went over my nutrition and weight, both of which he felt were satisfactory. Nevertheless, my wife and I met with a nutritionist from the clinic who carefully reviewed my caloric intake and food preferences, and gave recommendations to help maintain my fluid and caloric intake, especially should I have severe esophageal pain from chest radiation.

	PSYCHOSTIMULANT MEDICATION

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
Knowing that my fatigue seemed unrelated to, and much greater than what could be explained by, one or more specific medical etiologies, but instead represented my body's submission to the cancer itself, I asked my oncologist whether methylphenidate hydrochloride (Ritalin^®; Novartis; East Hanover, NJ), the recently available of its longer-acting preparations, Concerta^® (ALZA; Mountain View, CA), or other longer-acting preparations—Ritalin-SR^®, Adderall^®, Adderall XR^TM, or Dexedrine SR might effectively help alleviate my cancer-induced fatigue. As a developmental pediatrician I am continually impressed with the benefits methylphenidate and other psychostimulant medications offer children with attention deficit disorder. As my oncologist could not identify any specific treatable cause of my fatigue—epoetin alfa raised my hematocrit, thereby restoring some of my energy, though with a negligible effect on my fatigue—and he had some experience with methylphenidate, having prescribed it for adults with end stage cancer, he agreed to my suggestion to prescribe one of the longer-acting psychostimulants, although he was not familiar with this particular medication.

After requesting the medication, however, I researched the use of psychostimulant medication to treat fatigue in people with cancer. While I found no study using methylphenidate or other psychostimulants for generalized cancer-related fatigue, I did find several interesting studies. First, I found a recent prospective study of 11 individuals with cancer treated with methylphenidate. All had advanced disease. The study asked 11 consecutive patients to agree to a trial of methylphenidate. The authors reported that eight of nine individuals showed a rapid onset of benefit from methylphenidate, even in the presence of anemia [2]. Methylphenidate also demonstrated benefits for hospitalized patients with cancer [3].

I also found reports of studies using psychostimulants in three other conditions; narcotic-induced sedation in children and adults, HIV/AIDS, and multiple sclerosis. First, methylphenidate and other psychostimulants were reported to safely counteract general narcotic-induced sedation in children [4] and adults [5], though with some limited benefit. Second, psychostimulant medication had recently proved effective in decreasing daily fatigue in individuals with HIV/AIDS [6]. Treatment not only reduced fatigue and provided increased energy for individuals with HIV, but also had a dramatic impact on measures of quality of life and psychological well-being, thus confirming that fatigue is a globally restricting condition, while tiredness presents as just one of its symptoms. The authors of this study concluded that the ability to adequately resolve even one common and distressing symptom for individuals with HIV appeared "worthwhile and necessary." Finally, psychostimulants were reported as a safe and effective treatment of fatigue in individuals with multiple sclerosis [7].

	BENEFITS

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
I started taking methylphenidate in the morning. My wife noted almost immediate benefits. She was overjoyed with my improved energy and enthusiasm. She was particularly happy with my increasing desire to go for walks, spend time with friends, go out at night—after work!—and just talk at the end of the day. She said my appearance was the most surprising change. I now didn’t look like I had cancer. On a couple of early occasions when I had forgotten to take the stimulant, she would invariably ask what was wrong, whether I was feeling okay.

Others shared her recognition of this change. My children expressed their joy at having their father back. I believe they saw me as less fragile, throwing off the ill-fitting veil of the victim, the sufferer, and the cancer patient, and instead emerging as their father, friend, and biggest fan. My liberation was apparent to them as well, my face and movements were clear evidence that while I had clearly recently stumbled, or more accurately crashed, and my body had perhaps absorbed a mortal blow, I was now the person with whom they could once again share their victories (large and small), as well as their challenges, their daily activities (from the mundane to the profound), and their concerns about me, all due to my replenished supply of emotional resources.

Though I did not notice the full degree of the changes in myself as quickly as my wife and others with whom I shared a close relationship, I did recognize having greater energy, more enthusiasm, less irritability, and better endurance. At work, I could once again fully engage in the developmental evaluations of young children. I was thrilled to again extract a response from even the most challenging of children, a furtive glance, an engaging smile, and a wondrous giggle. I could again maintain color in my face and air in my lungs while playing hide and seek, throwing a little boy in the air (and often catching him), roughhousing, and playing tickling games—their first experience with a contact sport—with these little beings. I even enjoyed their asking what happened to my hair, and their uninhibited laughter when we would search the clinic room for my former topping. We often concluded that I probably left it at home. No child agreed to my request to share their hair.

While the energy gains were real, they were occasionally tenuous. I noticed that the "crashes"—best explained as the feeling that a vacuum pump had rapidly and without warning instantaneously drained me of energy—still occurred. Now, however, the timing of these fog-inducing events was at least somewhat predictable. The first event occurred regularly at between 2:20 and 2:30 p.m.. After a while, I didn’t even need to check the clock. The second was a continuation of my late afternoon decline, coming with equal regularity, at 5:20-5:30. When I recognized that the first event marked the declining level of the medication, my oncologist agreed to add a second dose. Taking that dose at around 2:00 p.m. maintained a more constant medication level thereby quickly and efficiently solving not only that mid-afternoon problem but the latter one as well.

I also realized that I could adjust the medication dose, timing, and duration according to my personal needs. For example, taking the second dose later in the day—around 3:00-4:00 p.m.—might provide more ability to enjoy an evening out. Perhaps I could now plan the previously unheard of post-cancer diagnosis feat, dinner and a movie, or stay awake at a friend's house past 8:30. I could also tell my children they could again call late, as I would probably be watching "stupid people tricks" on The David Letterman Show.

I am considering changing my current medication to an even longer acting preparation. This change would likely provide continuous benefit throughout the day and even into the early evening. This effect could eliminate the necessity of the mid-afternoon dose, but perhaps eliminate the movie as well. The point is that I can design, with considerable flexibility, a regimen that works best for my family and me. I am now able to mobilize my own energy resources more frequently and with more predictability. I no longer feel defenseless against the physically and emotionally disabling cancer forces. While my oncologist thoughtfully chooses the heavy artillery, I now command some troops of my own. I feel that taking command has given me power perhaps to stop or at least help modify the assault. I now have control over an additional weapon. I have me.

	CONCLUSION

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
A careful and thorough consideration of conditions diminishing a person's quality of life is an essential strategy for the comprehensive treatment of people with cancer. Recruiting our available physical, emotional, and spiritual energy can be key to our ability to maintain our quality of life. It may also restore some balance and, thus, keep us in the battle, providing the physical and emotional energy to combat the uninvited and unwelcome invader.

Psychostimulant medication has been effective in treating my cancer-related fatigue. Further, I believe starting the medication before being dulled by opiates or becoming overcome by depression or end-stage disease increased my potential to combat fatigue. While studies to critically evaluate the efficacy of psychostimulants for children and adults are clearly needed, their proven success treating fatigue in other medical conditions, as well as recognized benefits for use in end-stage disease, and most importantly, their record of safety—undoubtedly the safest, most effective, and most studied medication prescribed by pediatricians—strongly support the need for oncologists to discuss and support this treatment option with all adults with cancer, with children who are mature minors and can give assent to their own treatment, and with parents of children over 6 years of age. Further, these discussions should begin when individuals with cancer and their families are told about the probability of fatigue. Learning that they may have a weapon against this disabling side effect may enhance their resolve and their recognition that their oncologist wants them to join the battle.

So, here's the bottom line. F the new F word.

	ACKNOWLEDGMENT

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 
Undying admiration and thanks to my tireless oncologist, Thomas Lynch, M.D., and to my family for making me want to continue to reach to them. You are my meaning.

	ADDITIONAL READING

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

 

Homsi J, Walsh D, Nelson KA. Psychostimulants in supportive care. Support Care Cancer 2000;8:385–397.[CrossRef][Medline]

Portenoy RK. Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. J Pain Symptom Manage 1989;4(suppl 3):2–4.[CrossRef][Medline]

	REFERENCES

Top Introduction Why Treat Fatigue? Medical Conditions Causing... Psychostimulant Medication Benefits Conclusion References Additional Reading

1. Frankel VE. Man's Search for Meaning. New York: Washington Square Press, 1959:137-138.
2. Sarhill N, Walsh D, Nelson KA et al. Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study. Am J Hosp Palliat Care 2001;18:187–192.[Abstract/Free Full Text]
3. Olin J, Masand P. Psychostimulants for depression in hospitalized cancer patients. Psychosomatics 1996;37:57–62.[Abstract/Free Full Text]
4. Yee JD, Berde CB. Dextroamphetamine or methylphenidate as adjuvants to opioid analgesia for adolescents with cancer. J Pain Symptom Manage 1994;9:122–125.[CrossRef][Medline]
5. Wilwerding MB, Loprinzi CL, Mailliard JA et al. A randomized, crossover evaluation of methylphenidate in cancer patients receiving strong narcotics. Support Care Cancer 1995;3:135–138.[CrossRef][Medline]
6. Breitbart W, Rosenfeld B, Kaim M et al. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Arch Intern Med 2001;161:411–420.[Abstract/Free Full Text]
7. Krupp LB, Coyle PK, Cross AH. Amelioration of fatigue with pemoline in patients with multiple sclerosis. Ann Neurol 1989;26:155–156.

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				K. L. Wharton The Person With Cancer and Quality of Life Oncologist, August 1, 2002; 7(4): 383 - 383. [Full Text] [PDF]

This Article Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wharton, R. H. Search for Related Content PubMed PubMed Citation Articles by Wharton, R. H.