International | Opioids

The problem of pain

Americans are increasingly addicted to opioids. Meanwhile people in poor countries die in agony without them

|KANO AND THIRUVANANTHAPURAM

DEVIN LYALL had experimented with drugs recreationally as a teenager before a doctor in her hometown of North Wilkesboro, North Carolina prescribed her opioid painkillers after an ankle surgery. But it was only when she began taking Vicodin—one of the most popular prescription opioids—that she became an addict. She relished the sense of invincibility it gave her and began swapping her pills for stronger opioids on the black market. When that became a hassle, she found a doctor who would prescribe her harder stuff, such as Roxicodone. It was not difficult, she recalls from her office at the North Wilkesboro addiction-treatment centre she opened in February, after three years of sobriety. “It was easy to figure out which doctors were prescribing what,” she says.

Opioid painkillers stimulate receptors in the brain and elsewhere to produce a powerful pain-numbing effect. They also lessen anxiety and depression—two common side-effects of intense pain. The sensation they induce is often described as euphoria. Some, such as morphine, are made from the opium poppy; others, such as oxycodone, are semi-synthetic or synthetic. They are highly addictive: even brief use can be followed by withdrawal symptoms. As a result, for most of the 20th century they were usually reserved for acute pain, after a serious accident or surgery, say, and palliative care, a branch of medicine dedicated to curbing the pain of those with illnesses such as cancer or AIDS.

But in the 1980s a series of papers by American researchers claimed that opioids could be used safely for longer periods. The evidence was slight, but, combined with a formidable marketing effort by drug firms, it led to American doctors prescribing opioids with abandon for chronic, non-terminal pain. According to America’s Centres for Disease Control (CDC), between 1994 and 2006 the share of American adults who had used prescription opioids in a given month jumped from 3.4% to nearly 7%. In 2012 doctors wrote almost 282m prescriptions for opioids—enough for a bottle each for every adult. Americans guzzle six times more prescription opioids per person than 20 years ago.

Everybody hurts

These doctors doubtless wanted to help patients in pain to lead happier, more active lives. However, America’s fee-for-service health model also gave them a financial incentive to provide patients with what they asked for—especially if it led to repeat prescriptions. Whatever the motivation, haphazard clinical practice and spotty oversight led to addiction and death. In 1999-2014 more than 165,000 Americans died from prescription-opioid overdoses. The typical victim was poor, white and single—though wealthy people are not immune. A definitive diagnosis will have to wait until the results of his autopsy, but some suspect that Prince, a musician who died unexpectedly last month, was a victim of prescription painkillers.

Opioids kill by slowing the respiratory system. A person who has taken too many—or who combines a standard dose with depressants such as alcohol, anti-anxiety pills or sleeping aids—may lose consciousness and stop breathing. According to the National Safety Council, an American non-profit, the difference between an effective and a lethal dose is “small and unpredictable”. Data are patchy, but state statistics suggest that many victims of opioid poisoning have legitimate prescriptions for chronic pain.

Newer evidence suggests that other drugs might be better for chronic pain. Andrew Kolodny of Physicians for Responsible Opioid Prescribing, an advocacy and research group, says that a combination of non-opioids, such as paracetamol and ibuprofen, can relieve acute pain at least as well—and certainly more safely.

A handful of other rich countries are struggling with opioid misuse, too. Canadians are increasingly getting hooked on and killed by the drugs, says Benedikt Fischer, who studies prescription-drug misuse at the University of Toronto’s Centre for Addiction and Mental Health. Britain, by contrast, has largely avoided creating opioid addicts. According to Cathy Stannard, a pain specialist at Southmead Hospital in Bristol, its publicly funded national health-care system means doctors have no incentive to over-prescribe. And prescription records are held centrally, so a patient bouncing from doctor to doctor in search of pain pills would quickly be spotted.

America is at last starting to wake up to its opioid scourge. The CDC recently released guidelines that urged increased caution when prescribing opioids to non-cancer patients. Prescriptions have declined by more than 10% nationally since the peak in 2012. In February the president, Barack Obama, said he would seek $1.1 billion in new funding for opioid-addiction treatments. Congress responded by passing 18 opioid-related bills in May. In many states doctors must now check databases to ensure that patients have not already been prescribed opioids elsewhere (though they can still get hold of pills in more than one state without triggering an alarm). The Drug Enforcement Agency (DEA) has cracked down on “pill mills” that reaped handsome profits from prescribing opioids to anyone who showed up to claim them.

Tighter prescribing is essential. But it has caused unintended harm. Heather Ratcliff of Petaluma, California, suffers from Ehlers-Danlos Syndrome, a degenerative disease; her tendons and ligaments do not properly secure her bones. A hearty laugh or unexpected sneeze is enough to dislocate her ribs. She tried acupuncture, osteopathic manipulative treatment and several other pain-relief methods before finally turning to opioids. “I hate them,” she says. “I hate how they make me feel—foggy-headed and slow. I hate how people assume people who consistently use opioids are addicts. But I need them.”

Of late, Ms Ratcliff has found her medication harder to get. Her hydrocodone was cut off by a doctor when she tested positive for cannabis—even though she had previously disclosed her use of the drug, and had a medical licence for it. She says that these days doctors and pharmacists are jumpier about DEA scrutiny, which in extreme cases can lead to licences being revoked. On one occasion a pharmacist refused to fill a prescription.

The squeeze has also caused a startling heroin problem. People cut off from prescription opioids sometimes turn to heroin, which offers a similar high and is cheap and easy to score on the street. According to the American government’s National Survey on Drug Use and Health, four out of five heroin users had progressed from opioid pain-relievers. In 2014 nearly as many Americans died from heroin and prescription opioids as from traffic accidents. Pregnant users are giving birth to addicted babies. They suffer the same symptoms as an adult undergoing withdrawal: tremors, vomiting and fever.

If in America the problem is over-prescription, in Russia it is the opposite: opioids are too hard to come by. In 2014 a retired admiral in Moscow with pancreatic cancer shot himself when his wife tried but failed to procure opioids for him. He left a note saying that the blame lay entirely with the health ministry and the government. He was one of about 40 Russians to have committed suicide in a single year because of unbearable pain, estimates the Lancet, a British medical journal.

Globally, such situations are far more common than the overuse seen in America. In poor and middle-income countries, people suffering from cancer and other terminal illnesses often die excruciating deaths with minimal relief. The International Narcotics Control Board (INCB), an independent monitor that oversees the implementation of UN drug conventions, estimates that 92% of all morphine, an opioid commonly used to control the pain caused by cancer, is consumed in America, Canada, New Zealand, Australia, and parts of western Europe—which between them hold only 17% of the world’s population. “It’s an absurd situation,” says Dr Fischer, the Canadian professor. “We’re spraying [opioids] from a fire-hose while the majority of the world doesn’t have them.”

House of pain

Access to pain relief in Nigeria has improved a bit since the country started importing morphine in 2012. But pharmacists from hospitals outside Lagos, the commercial capital, must travel there to buy morphine. Smaller hospitals struggle to pay for the trip. Aminu Kano, a hospital in the country’s north, is one of those that manages to procure opiates. Even so, a visit turns up distressing scenes. A burns victim lies deathly still under crisp white sheets, the skin on his face peeled back. More than half his body was set alight when a gas hob exploded in his house, but he is given no morphine. His brother says that at night he wakes up screaming from the pain.

Down a leafy walkway, a mother straps her three-year-old daughter to her back. One side of the child’s face presses up against her; on the other, a growth the size of an orange protrudes from the socket where her eye should be. She has a rare kind of cancer called retinoblastoma. Her family must pay 120,000 naira ($600) each time she receives chemotherapy. When the money runs out, the pair leave. “At home there is no help for her pain,” the mother says. “The pain will be eating her, and all I can do to cool her down is pet her.”

Most palliative-care professionals, in Nigeria and elsewhere in the developing world, are found in cities. That makes it hard for rural patients to get treatment for their suffering. Gayatri Palat, a professor of pain and palliative medicine at the MNJ Institute of Oncology and Regional Cancer Centre in Hyderabad, India, recalls a former patient, a child with cancer. He had visited several clinics nearer his home in search of pain relief before stumbling into her hospital, ragged and short of breath. It had taken him more than 12 hours to get there, and he died soon afterwards. In Tenkasi, a rural town in India’s humid south, Samuel Samudra, a gaunt 60-year-old, was discharged from surgery for throat cancer. By the time he arrived at Pallium India, a small palliative-care hospital in Thiruvananthapuram, the state capital of Kerala, the operative wound on his throat was infested with maggots. For pain relief, he had only over-the-counter pills.

When illness strikes, patients in poor countries expect to suffer. Even when the tumour on his hip grew to the size of a football, Mato Samaile, a frail 50-year-old Nigerian cattle farmer, was reluctant to go to hospital. “When I found the lump I said to my son: ‘We can’t leave the farm. We should stay until after the rain falls,’” he says from his bed in Aminu Kano. “People are brought up to tolerate pain,” says Amina Ibrahim, a surgeon at the hospital. “If you don’t you are a coward. That is just our culture. So even doctors are not liberal on painkillers.”

Though Colombia produces its own opioid painkillers, some regional governments either cannot afford to buy them from the federal government, or regard them as a low priority.

And patients often associate morphine with imminent death, says Marta Ximena León of the palliative care and pain group at the University of La Sabana in Colombia. She recalls meeting cancer patients who begged not to be given the drugs. “They felt that if they were prescribed morphine, that meant there was nothing else that could be done for them,” she says.

Doctors in many places are also wary. In India, Dr Palat explains, their training includes very little about pain management. A report in 2009 by Human Rights Watch, a pressure group, found that of some 300 Indian medical colleges, only five taught palliative care. The consequence is that few doctors know how to prescribe opioids safely. Even for patients with advanced cancer, they avoid morphine, says Dr Palat: “They’re afraid it will cause addiction in healthier patients or respiratory depression in those with terminal illnesses.” Similar worries in India’s north-eastern neighbour, Nepal, meant that 50% of the country’s supply of sustained-release morphine tablets went unused in 2011. M.R. Rajagopal, the head of Pallium India, says that news of the opioid crisis in America has only heightened such fears.

Show me where it hurts

Pain management is simply not a priority for governments in much of the developing world, says Meg O’Brien, the managing director of global cancer treatment at the American Cancer Society. Many focus on life-threatening epidemics rather than treating pain, she says. “No one gets in trouble if, at the end of the year, pain relief has not been procured.”

The lack of opioids across the developing world is particularly striking, because the drugs are cheap to make, and the raw ingredients plentiful. Estimates suggest that the global harvest of opium poppies, from which natural and semi-synthetic opioid medications such as morphine and codeine are prepared, together with the chemicals for synthetic ones, should be enough to satisfy all the demand in the world. Few opioids are patented; a monthly dose of morphine should cost just $2-5.

But paltry prices can work against developing countries, says James Cleary, a palliative-care specialist at the University of Wisconsin: they mean drug firms have little incentive to bring them to new markets. Tariffs, import licences and high costs for small-scale local production mean that morphine can cost twice as much in poor places as rich ones. Some countries, such as Jamaica, subsidise opioid painkillers. Many others do not.

Untreated suffering used to be the norm in the developed world, too. Even after the advent of modern painkillers, it took changing attitudes on the part of patients, doctors and governments before they became widely used. Opioids are now understood to be the most effective and humane treatment for terminal pain, and also appropriate in many cases of acute pain.

The rest of the world would probably have seen the same progression in recent years—had it not been for the “war on drugs” that America launched with such fanfare half a century ago. The INCB has a dual mandate: to increase access to controlled substances for medical purposes and to stop their illicit use. Many governments, however, pay little attention to the first of those aims and focus instead on the second. With no impetus for wider prescribing from doctors, patients or governments, inertia and bureaucracy rule.

To try to stop leakage onto the black market, the INCB requires countries wishing to import opioid painkillers to provide estimates of the quantity they expect to use in the coming year. If the board deems the request reasonable, it is approved. But many countries decide how much to ask for by looking at past consumption, thereby underestimating current need. Senegal, for example, has asked for a similar morphine quota each year since the 1960s. In 2013 it applied for only 1 kilo of morphine—about enough to soothe the pain of 200 patients with advanced cancer.

The Russian admiral who committed suicide appears to have been denied opioid painkillers because his stacks of paperwork were missing one essential signature. Shortly after his death, his daughter wrote on her Facebook page: “To get a five days’ supply of [morphine], one has to spend many hours dashing between many doctors’ office in the clinic, [even] spend a few days. By the day’s end, one signature was still required and the clinic closed. My father was outraged. It was the last straw.”

In a recent report Human Rights Watch detailed the Byzantine process cancer patients must follow to procure morphine in Armenia. First patients are diagnosed by an oncologist and their diagnosis is confirmed through a biopsy, a procedure only a few Armenian hospitals perform. The oncologist must then try a series of weaker pain medicines before asking a panel for permission to use morphine. Five specialists assess the situation and either confirm or deny the prescription, which then needs to be authorised with four stamps and three signatures. A patient lucky enough to receive an authorised prescription must travel to one of the few clinics or pharmacies where morphine is stored and will receive only enough for a few days.

Such rules are far more restrictive than anything in the UN’s drug conventions, says Diederik Lohman, who works on palliative care for Human Rights Watch. “Countries have been told ‘you have to crack down on drugs: the harsher the better,’” he explains. “For many years, drug strategies published by the international community and the United States did not mention the medical importance of certain controlled substances.” A 1998 UN declaration begins: “Drugs destroy lives and communities, undermine sustainable human development, and generate crime.” Nowhere does it refer to medical uses. For most patients in the developing world, untreated pain is the status quo and therefore they do not agitate against severe controls as their peers in the rich world might.

A handful of countries, including India, Ukraine and Colombia, have recently amended their laws to make it easier for patients who need them to be given opioids, though doctors say that implementation is slow. Some others have started producing their own morphine, or importing morphine powder which is less controlled and can be whizzed into orally administered syrup. Such changes mean that, since 2003, opioid consumption has increased in most regions. But much more must be done. The first step is to ensure that doctors—and patients—know that it is not necessary to die in pain.

Correction: An earlier version of this article overstated the number of precriptions for adults in 2011-12. It also overstated the decline in precriptions since the peak in 2012. These numbers have been corrected.

This article appeared in the International section of the print edition under the headline "The problem of pain"

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