Symptom Clusters: Pain, Depression, and Fatigue

JNCI Monographs 2004 2004(32):119-123; doi:10.1093/jncimonographs/lgh028
Abstract


There is not yet sufficient evidence-based experience for the coordinated treatment of three symptoms that cluster in cancer: pain, depression, and fatigue. Each symptom taken individually has accepted treatment modalities. With some overlap between these symptoms, established treatments for one symptom may "cross-over" and reduce the burden of one, or both of the others. To optimize patient care in advance of the evidence basis, attention to these symptoms is value-added for patients and their families. Standardized screening using the Distress Thermometer for physical, practical, emotional, or spiritual symptoms helps effectively identify patients whose symptoms warrant attention. Cancer Supportive Services, an innovative program at the Continuum Cancer Centers of New York at Beth Israel and St. Luke’s-Roosevelt, provides comprehensive intervention throughout the trajectory of care for pain, depression, and fatigue. These services are provided in tandem with efforts to cure or contain the cancer. Cancer Supportive Services sets up a natural entry point to survivors’ follow-up or end-of-life care. Such an effort reinforces a basic principle that active symptom management is integral to each patient encounter in the cancer treatment setting.

Introduction


There are many dimensions to patients’ experience with cancer. Certain experiences, or symptoms, are shared by most patients with cancer. As discussed elsewhere, three of those symptoms, pain, fatigue, and depression often track together in the same individual. Taking the type of cancer, stage, and treatment into account, subjective evaluation of these predictable commonalities is colored by the extent to which his or her cancer can be treated or cured, individual psychology, and effective social or spiritual support.


Until the recent past, these symptoms were silently tolerated as a consequence of cancer and its treatment. If identified at all, they were considered as part of the burden one pays when living with life-threatening illness and perhaps as surrogates for the extent of disease or treatment response. Modern biotechnology, and the extended survival of patients with some cancers, has brought focus to these symptoms and expanded the opportunity for intervention. The strengthened sense of consumerism coupled with faster multimedia communications’ information explosion have sparked demand for the treatment of pain, fatigue, and depression before rigorous studies of the triad have been completed.


The question at hand—What is the optimal treatment of symptom clusters?—challenges the underpinnings of medical decision making developed throughout the twentieth century as well as the notion of evidence-based medicine popularized at the century’s close. Accurate diagnoses, made with uniform and accepted criteria in mind, precede the formation of a treatment plan. Treatment, when instituted, is based on evidence from controlled trials as the gold standard taking precedence over clinician familiarity or past experience.


Separating the constitutional signs and symptoms of cancer itself from those of depression has become more feasible through collective experience and research, though the process is still somewhat inexact. Challenging the popular notion that all cancer patients suffer depression has led to a dilemma: defining degrees of depression in the wide variety of cancer illnesses at its various stages and with its confounding treatments, and then designing proper treatment for these mood changes. Tradition asks that a diagnosis be established before a treatment plan is set. Estimating the contribution of mood to the experience of cancer underscores the very basic property of mood as a background emotion to the life experiences that occur around it.


With a parallel interest in diagnosing and treating pain and fatigue, the ever-present contribution of mood complicates the understanding of these symptoms in cancer. Not every patient experiences pain or fatigue to the same degree, and culture and personal values overlay these symptoms as well. Looking at each symptom separately, it should be clear that their presentation and measurement have substantial overlap, so it is reasonable to assume that respective treatments would overlap as well.


Critical thinking forces us to first look at accepted treatment modalities for each symptom in isolation, drawing on what is known about the symptom in general: depression in the physically healthy, fatigue in those without depression or cancer, and pain from a variety of causes. The subsequent challenge is to adapt these "pure" circumstances across the spectrum of cancer and its treatments, adjusting for age and comorbidities.


With an evidence-based focus, the next step to approaching the treatment of symptom clusters is to survey published data examining cluster treatments across the lifespan and among various cancers. Articles describing findings of these clusters do not exist. An innovative methodological adaptation is to take the usual and generally acceptable treatment modalities used for a single cancer symptom and examine its efficacy in the remaining two symptoms. The notion of "clustering" of pain, fatigue, and depression is born out of the impression that a treatment modality commonly used in one symptom can reduce the burden of the others.

© 2004 by Oxford University Press

Pain care for the world's poor

The New York Times
September 10, 2007Drugs Banned, Many of World’s Poor Suffer in Pain
By DONALD G. McNEIL Jr.

WATERLOO, Sierra Leone — Although the rainy season was coming on fast, Zainabu Sesay was in no shape to help her husband. Ditches had to be dug to protect their cassava and peanuts, and their mud hut’s palm roof was sliding off.

But Mrs. Sesay was sick. She had breast cancer in a form that Western doctors rarely see anymore — the tumor had burst through her skin, looking like a putrid head of cauliflower weeping small amounts of blood at its edges.

“It bone! It booonnnne lie de fi-yuh!” she said of the pain — it burns like fire — in Krio, the blended language spoken in this country where British colonizers resettled freed slaves.

No one had directly told her yet, but there was no hope — the cancer was also in her lymph glands and ribs.

Like millions of others in the world’s poorest countries, she is destined to die in pain. She cannot get the drug she needs — one that is cheap, effective, perfectly legal for medical uses under treaties signed by virtually every country, made in large quantities, and has been around since Hippocrates praised its source, the opium poppy. She cannot get morphine.

That is not merely because of her poverty, or that of Sierra Leone. Narcotics incite fear: doctors fear addicting patients, and law enforcement officials fear drug crime. Often, the government elite who can afford medicine for themselves are indifferent to the sufferings of the poor.

The World Health Organization estimates that 4.8 million people a year with moderate to severe cancer pain receive no appropriate treatment. Nor do another 1.4 million with late-stage AIDS. For other causes of lingering pain — burns, car accidents, gunshots, diabetic nerve damage, sickle-cell disease and so on — it issues no estimates but believes that millions go untreated.

Figures gathered by the International Narcotics Control Board, a United Nations agency, make it clear: citizens of rich nations suffer less. Six countries — the United States, Canada, France, Germany, Britain and Australia — consume 79 percent of the world’s morphine, according to a 2005 estimate. The poor and middle-income countries where 80 percent of the world’s people live consumed only about 6 percent.

Some countries imported virtually none. “Even if the president gets cancer pain, he will get no analgesia,” said Willem Scholten, a World Health Organization official who studies the issue.

In 2004, consumption of morphine per person in the United States was about 17,000 times that in Sierra Leone.

At pain conferences, doctors from Africa describe patients whose pain is so bad that they have chosen other remedies: hanging themselves or throwing themselves in front of trucks.

Westerners tend to assume that most people in tropical countries die of malaria, AIDS, worm diseases and unpronounceable ills. But as vaccines, antibiotics and AIDS drugs become more common, more and more are surviving past measles, infections, birth complications and other sources of a quick death. They grow old enough to die slowly of cancer.

About half the six million cancer deaths in the world last year were in poor countries, and most diagnoses were made late, when death was inevitable. But first, there was agony. About 80 percent of all cancer victims suffer severe pain, the W.H.O. estimates, as do half of those dying of AIDS.

Morphine’s raw ingredient — opium — is not in short supply. Poppies are grown for heroin, of course, in Afghanistan and elsewhere. But vast fields for morphine and codeine are also grown in India, Turkey, France, Australia and other countries.

Nor is it expensive, even by the standards of developing nations. One hospice in Uganda, for example, mixes its own liquid morphine so cheaply that a three-week supply costs less than a loaf of bread.

Nonetheless, it is still routinely denied in many poor countries.

“It’s the intense fear of addiction, which is often misunderstood,” said David E. Joranson, director of the Pain Policy Study Group at the University of Wisconsin’s medical school, who has worked to change drugs laws around the world. “Pain relief hasn’t been given as much attention as the war on drugs has.”

Doctors in developing countries, he explained, often have beliefs about narcotics that prevailed in Western medical schools decades ago — that they are inevitably addictive, carry high risks of killing patients and must be used sparingly, even if patients suffer.

Pain experts argue that it is cruel to deny them to the dying and that patients who recover from pain can usually be weaned off. Withdrawal symptoms are inevitable, they say — as they are if a diabetic stops insulin. But the benefits outweigh the risks.

Too Poor for Medicine

In Mrs. Sesay’s case, Alfred Lewis, a nurse from Shepherd’s Hospice, is doing what he can to ease her last days.

When he first saw her, her tumor was wrapped with clay and leaves prescribed by a local healer. The smell of her rotting skin made her feel ashamed.

She had seen a doctor at one of many low-cost “Indian clinics” who pulled at the breast with forceps so hard that she screamed, misdiagnosed her tumor as an infected boil, and gave her an injection in her buttocks that abscessed, adding to her misery.

Nothing can be done about the tumor, Mr. Lewis explained quietly. “All the bleeders are open,” he said. “Her risk now is hemorrhage. Only a knife-crazy surgeon would attend to her.”

Earlier diagnosis would probably not have changed her fate. Sierra Leone has no CAT scanners, and only one private hospital offers chemotherapy drug treatment. The Sesays are sharecroppers; they have no money.

So Mr. Lewis was making a daily 10-mile trip from Freetown, the capital, to change her dressing, sprinkle on antibiotics, and talk to her. He asked a neighbor to plait her hair for her, so she would look pretty. Mrs. Sesay said she could not be bothered.

“It’s necessary for to cope,” he said. “For to strive for be happy.”

“I ‘fraid for my life,” she said.

“Are you ‘fraid for die?”

“No, I not ‘fraid. I ready.”

“So what is your relationship to God? You good with God?”

“I pray me one.”

He asked her, half-jokingly, if she still had sex with her husband.

No, she said, since the illness, he stayed in his room and she stayed in hers. She, too, was joking. In their hut, there is only the one room.

Life has become hard, she added, and her husband is getting too old for farm labor. She, too, is getting old, she said — she is somewhere in her 40s.

“We are really being punish.”

For her pain, Mr. Lewis gave her generic Tylenol and tramadol, a relative of codeine that is only 10 percent as potent as morphine. It was all he could offer. “I would consider putting her on morphine now, if we had morphine,” Mr. Lewis said.

In New York, she would have already started on it, or an equivalent like oxycodone or fentanyl.

Even if his hospice could get it, Mr. Lewis could not give it to her.

Under Sierra Leone law, morphine may be handled only by a pharmacist or doctor, explained Gabriel Madiye, the hospice’s founder. But in all Sierra Leone there are only about 100 doctors — one for every 54,000 people, compared with one for every 350 in the United States.

In only a few places — in Uganda, for example — does the law allow trained nurses to prescribe morphine.

And pharmacists will not stock it.

“It’s opioid phobia,” Mr. Madiye said. “We are coming out of a war where a lot of human rights violations were caused by drug abuse.”

During the war, the rebel assault on the capital was called Operation No Living Thing. Child soldiers were hardened with mysterious drugs with names like gunpowder and brown-brown, along with glue and alcohol.

Esther Walker, a British nurse who sometimes works with Mr. Lewis, said she once gave a lecture on palliative care at the national medical school.

There were 28 students, and she asked them, “Who has seen someone die peacefully in Sierra Leone?”

“Not one had,” she said.

The Burden on the Young

In the poorest countries like this one, even babies suffer.

Momoh Sesay, 2, (no relation to Zainabu) is a pretty lucky little guy — for someone who tumbled into a cooking pot of boiling water.

He lost much of the skin on his thighs, and his belly is speckled with burns as if he had been sloshed with pink paint.

But he was fortunate enough to live close to Ola During Children’s Hospital, the leading pediatric institution.

No doctor was in. There was not even any electricity. At night, nurses thread IV lines into babies’ tiny limbs by candlelight. “And our eyes are not magnets,” one of them, Josephine Maajenneh Sillah, complained.

But they knew Momoh would die of shock and pumped in intravenous fluids and antibiotics.

If he had been born in New York, Momoh would have had skin grafts. Here, that is unthinkable.

Momoh was given saline washes, and his dead skin was scrubbed off with debridement, a painful procedure. In New York, he would have had morphine.

So probably would Abdulaziz Sankoh, 7, in another bed, who has sickle cell disease. He moans at night when twisted blood cells clump together and jam the arteries in his spindly legs, slowly killing his bone marrow.

As would Musa Shariff, an 8-month-old boy whose scalp is so swollen by meningitis that his eyelids cannot close. Dr. Muctar Jalloh, the hospital director, said he would not prescribe morphine to babies or toddlers if he had it. Only in the case of third-degree burns, like Momoh’s, did he say: “I would consider it — maybe.”

That flies in the face of Western medicine, which allows careful use even in premature infants.

The strongest painkiller that Momoh, Abdulaziz and Musa can take, if their parents can afford $1.65 per vial, is tramadol. It is impossible to know what morphine would cost if it were here, but it is sold in India at 1.7 cents a pill by the same company that makes tramadol.

The nurses know the prices because they sell the drugs that are available. They have not been paid for three years, they say, so they support themselves in part by filling the prescriptions that the doctors write. Kind as they are — they do extend credit, and are sometimes moved to charity by the children — it is a business.

That is the other reason Dr. Jalloh said he would not order morphine. “I wouldn’t want to leave my staff in charge of morphine,” he said. “The potential for abuse is so high.”

Worries About Abuse

If morphine were to be imported to Sierra Leone, it would be overseen by two agencies: the National Pharmacy Board and the National Drugs Control Agency.

Kande Bangura, the rangy, sharp-eyed former police commander who runs the drug control agency, said the country had a serious drug-abuse problem, especially among former child soldiers.

It also is a smuggling route. He spread out pictures of an autopsy on a British citizen with Nigerian roots who had dropped dead in line at Freetown’s airport. His intestines were found to be packed with condoms full of cocaine, one of which had burst.

Mr. Bangura said he had no objections to morphine, however, “as long as it’s for medical use and is strictly controlled by the country’s chief pharmacist.”

Wiltshire C. N. Johnson, the chief of the enforcement arm of the National Pharmacy Board, explained why painkillers were not imported.

Scarce funds must go to the top five causes of death, he said: diarrhea, pneumonia, tuberculosis, malaria and sexually transmitted diseases. “I’m not saying that palliative care doesn’t top the list, too,” he said. “But it’s officially a very small percentage of the requirement.”

He also had fears like those of Dr. Jalloh. “There’s no way we’re going to put morphine in the hands of a pharmacy technician,” he said. “In the wrong hands, drugs, like guns, are a greater evil than a cure.”

Mr. Madiye, who predicted exactly those answers before the interviews started, vented his frustration later.

He founded Shepherd’s Hospice in 1995, saw it destroyed in the civil war and rebuilt it. But he cannot get the one drug that would let him give people like Zainabu Sesay the dignified deaths that in the West would be their birthright.

“How can they say there is no demand when they don’t allow it?” he asked. “How can they be so sure that it will get out of control when they haven’t even tried it?”