We attribute the recent quadrupling of heroin death rates to the August, 2010 reformulation of an oft-abused prescription opioid, Oxycontin. The new abuse-deterrent formulation led many consumers to substitute to an inexpensive alternative, heroin. Using structural break techniques and a difference-in-differences analysis, we find that opioid consumption stops rising in August, 2010, heroin deaths begin climbing the following month, and growth in heroin deaths was greater in areas more likely to substitute from opioids to heroin. The reformulation did not generate a reduction in combined heroin and opioid mortality—each prevented opioid death was replaced with a heroin death.
.. OxyContin is a name-brand opioid pain killer marketed by Purdue Pharma.13 The active ingredient in OxyContin is Oxycodone, an opioid that has been in clinical use since 1917 (Kalso, 2005) and is the active ingredient in such pharmaceuticals as Percodan (Oxycodone and aspirin) and Percocet (Oxycodone and Tylenol). OxyContin is an extended-release formulation that allows for up to 12 hours of pain relief and hence there is typically a high milligram (mg) content of Oxycodone in the pills.14 Since its release in 1996, OxyContin has been one of the most successful pharmaceuticals of all time with worldwide sales totaling $35 billion.15
.. OxyContin was introduced at a time when the medical profession was beginning to re-evaluate its use of opioid-based pain killers. Historically, opioids were reserved for those with acute pain such as postsurgical and cancer patients. Given the limited use of opioids, pain from chronic conditions often went untreated. This was viewed by many as a failure of the medical profession. In the middle 1990s, a number of physicians began to argue for much greater use of opioids for patients with chronic pain. In the 1995 presidential address of the American Pain Society, James Campbell introduced the notion that pain is the “5th vital sign.” Campbell (1995) argued that “Quality care means pain is measured. Quality of care means pain is treated.”
.. an important study used by Purdue Pharma in their advertising materials, Porter and Jick (1980), reported that of “11,882 patients who received at least one narcotic preparation [opioid], there were only four cases of reasonably well documented addiction in patients who had no history of addiction.”
.. This “study” was in actuality a 100-word letter to the editor in the New England Journal of Medicine, the entire substance of which is contained in the quote above.
.. in 1996, the FDA allowed Purdue Pharma to claim that addiction was rare if opioids were legitimately used in the treatment of pain.
.. Between 1996, when OxyContin was released, and 2003, sales of OxyContin increased from $44.8 million to $1.5 billion per year (United States General Accounting Office, 2003)
.. The movement to an abuse-deterrent formulation made OxyContin less desirable for recreational use.
.. Of confiscated heroin, 79 percent is now from Mexico
.. The price has fallen from more than $3,000 per pure gram in 1981 to less than $500 in 2012
.. Groups like the Xalisco Boys have transformed the supply of heroin to suburban and rural US markets. Within their distribution network, independent “cells” within a city are operated by cell managers and each cell is supplied with high-quality Mexican heroin by the cell’s owner. The cell manager employs a telephone operator who receives orders and then relays those orders to the drivers. A driver meets the client at a designated spot or delivers the drugs directly to the customer’s location. Each cell operates almost completely independently and constantly cycles through lower level employees to help prevent detection by authorities.
.. 30 years ago, the typical heroin user was an urban resident. Heroin use in the 1990s and 2000s has now “spread to users in suburban and rural areas, more affluent users, younger users, and users of a wider range of ages. There is no longer a typical heroin user.” The entry into heroin is now much easier because of the purity level. In the 1970s, heroin was mostly an injected drug. Because of increased purity, the drug can now be smoked or inhaled, decreasing the cost of drug initiation
.. the costs of the opioid crisis seem to be driven primarily by the costs associated with mortality. Inocencio et al. (2013) put the total costs at $20.4 billion in 2011 dollars, but 89 percent of these costs, more than $18 billion, are due to lost earnings from higher mortality. Although we do not do a formal cost-benefit analysis, the fact is that Purdue Pharma’s abuse-deterrent formulation of OxyContin was unable to affect the vast majority of the crisis’s costs.
.. While some individuals die from heroin overdoses shortly after initiation, on average, it takes between 5 and 10 years for a heroin user to overdose and die
The Sackler dynasty’s ruthless marketing of painkillers has generated billions of dollars—and millions of addicts.
An addiction specialist said that the Sacklers’ firm, Purdue Pharma, bears the “lion’s share” of the blame for the opioid crisis.
.. The Brooklyn-born brothers Arthur, Mortimer, and Raymond Sackler, all physicians, donated lavishly during their lifetimes to an astounding range of institutions, many of which today bear the family name: the Sackler Gallery, in Washington; the Sackler Museum, at Harvard; the Sackler Center for Arts Education, at the Guggenheim; the Sackler Wing at the Louvre; and Sackler institutes and facilities at Columbia, Oxford, and a dozen other universities. The Sacklers have endowed professorships and underwritten medical research. The art scholar Thomas Lawton once likened the eldest brother, Arthur, to “a modern Medici.
.. Marissa Sackler, the thirty-six-year-old daughter of Mortimer
.. she finds the word “philanthropy” old-fashioned. She considers herself a “social entrepreneur.”
.. When the Met was originally built, in 1880, one of its trustees, the lawyer Joseph Choate, gave a speech to Gilded Age industrialists who had gathered to celebrate its dedication, and, in a bid for their support, offered the sly observation that what philanthropy really buys is immortality:
.. the Sacklers are now one of America’s richest families, with a collective net worth of thirteen billion dollars—more than the Rockefellers or the Mellons.
.. Purdue Pharma—a privately held company, based in Stamford, Connecticut, that developed the prescription painkiller OxyContin.
.. four out of five people who try heroin today started with prescription painkillers.
.. a hundred and forty-five Americans now die every day from opioid overdoses.
.. it’s in 1996 that prescribing really takes off,” Kolodny said. “It’s not a coincidence. That was the year Purdue launched a multifaceted campaign that misinformed the medical community about the risks.” When I asked Kolodny how much of the blame Purdue bears for the current public-health crisis, he responded, “The lion’s share.”
.. Although the Sackler name can be found on dozens of buildings, Purdue’s Web site scarcely mentions the family, and a list of the company’s board of directors fails to include eight family members, from three generations, who serve in that capacity.
.. The Sacklers were especially interested in the biological aspects of psychiatric disorders, and in pharmaceutical alternatives to mid-century methods such as electroshock therapy and psychoanalysis.
.. In 1942, Arthur helped pay his medical-school tuition by taking a copywriting job
.. He recognized that selling new drugs requires a seduction of not just the patient but the doctor who writes the prescription.
.. in selling new drugs he devised campaigns that appealed directly to clinicians, placing splashy ads in medical journals and distributing literature to doctors’ offices. Seeing that physicians were most heavily influenced by their own peers, he enlisted prominent ones to endorse his products, and cited scientific studies (which were often underwritten by the pharmaceutical companies themselves).
.. “Most of the questionable practices that propelled the pharmaceutical industry into the scourge it is today can be attributed to Arthur Sackler.”
.. Arthur’s techniques were sometimes blatantly deceptive.
.. “More and more physicians find Sigmamycin the antibiotic therapy of choice.”
.. The Saturday Review tried to contact some of the doctors whose names were on the cards. They did not exist.
.. One Librium ad depicted a young woman carrying an armload of books, and suggested that even the quotidian anxiety a college freshman feels upon leaving home might be best handled with tranquillizers.
.. Win Gerson, who worked with Sackler at the agency, told the journalist Sam Quinones years later that the Valium campaign was a great success, in part because the drug was so effective. “It kind of made junkies of people, but that drug worked,”
.. By 1973, American doctors were writing more than a hundred million tranquillizer prescriptions a year, and countless patients became hooked.
.. He scoffed at suggestions that there was a conflict of interest between his roles as the head of a pharmaceutical-advertising company and the publisher of a periodical for doctors.
.. a company he owned, MD Publications, had paid the chief of the antibiotics division of the F.D.A., Henry Welch, nearly three hundred thousand dollars in exchange for Welch’s help in promoting certain drugs. Sometimes, when Welch was giving a speech, he inserted a drug’s advertising slogan into his remarks.
“The Sackler empire is a completely integrated operation in that it can
- devise a new drug in its drug development enterprise, have the drug clinically tested and
- secure favorable reports on the drug from the various hospitals with which they have connections,
- conceive the advertising approach and prepare the actual advertising copy with which to promote the drug,
- have the clinical articles as well as advertising copy published in their own medical journals, [and]
- prepare and plant articles in newspapers and magazines.”
.. A panel of senators assailed him with pointed questions, but he was a formidable interlocutor—slippery, aloof, and impeccably prepared—and no senator landed a blow.
.. Arthur’s children fought bitterly with Gillian, and sparred with Mortimer and Raymond, over the estate. They accused Gillian of trying to steal their inheritance, and of being “inspired variously by greed, malice, or vindictiveness toward her stepchildren.”
.. A family lawyer told the children, “There were no absolutely white lilies here on either side.”
.. for the Romans, the poppy was a symbol of both sleep and death.
.. MS Contin became the biggest seller in Purdue’s history. But, by the late eighties, its patent was about to expire, and Purdue executives started looking for a drug to replace it.
.. “In terms of narcotic firepower, OxyContin was a nuclear weapon.”
.. Highly regarded doctors, like Russell Portenoy, then a pain specialist at Memorial Sloan Kettering Cancer Center, in New York, spoke out about the problem of untreated chronic pain—and the wisdom of using opioids to treat it.
.. Describing opioids as a “gift from nature,” he said that they needed to be destigmatized.
.. claiming that it was indicative of “opiophobia,” and suggesting that concerns about addiction and abuse amounted to a “medical myth.”
.. the American Pain Society published a statement regarding the use of opioids to treat chronic pain. The statement was written by a committee chaired by Dr. J. David Haddox, a paid speaker for Purdue.
.. the F.D.A., in an unusual step, approved a package insert for OxyContin which announced that the drug was safer than rival painkillers, because the patented delayed-absorption mechanism
.. launched OxyContin with one of the biggest pharmaceutical marketing campaigns in history
.. A major thrust of the sales campaign was that OxyContin should be prescribed not merely for the kind of severe short-term pain associated with surgery or cancer but also for less acute, longer-lasting pain: arthritis, back pain, sports injuries, fibromyalgia.
.. Purdue similarly spoke of reaching patients who were “opioid naïve.”
.. “the goal should have been to sell the least dose of the drug to the smallest number of patients.” But this approach was at odds with the competitive imperatives of a pharmaceutical company, he continued. So Purdue set out to do exactly the opposite.
.. Purdue had a speakers’ bureau, and it paid several thousand clinicians
.. The marketing of OxyContin relied on an empirical circularity: the company convinced doctors of the drug’s safety with literature that had been produced by doctors who were paid, or funded, by the company.
.. OxyContin’s success can be attributed partly to the fact that so many doctors wanted to believe in the therapeutic benefits of opioids.
.. Purdue gave money to continuing medical education, to state medical boards, to faux grassroots organizations.”
.. Purdue instructed sales representatives to assure doctors—repeatedly and without evidence—that “fewer than one per cent” of patients who took OxyContin became addicted. (In 1999, a Purdue-funded study of patients who used OxyContin for headaches found that the addiction rate was thirteen per cent.)
.. Internal budget plans described the company’s sales force as its “most valuable resource.” In 2001, Purdue Pharma paid forty million dollars in bonuses.
.. The fact that Purdue is privately held is a major reason that the Sacklers’ connection to OxyContin has remained obscure.
.. Mortimer Sackler .. He renounced his U.S. citizenship in 1974, reportedly for tax reasons, and lived a flamboyant life in Europe, shuttling among residences in England, the Swiss Alps, and Cap d’Antibes.
.. If you ground the pills up and snorted them, or dissolved them in liquid and injected them, you could override the time-release mechanism and deliver a huge narcotic payload all at once
.. Purdue insisted that the only problem was that recreational drug users were not taking OxyContin as directed.
.. One night, after four months on the drug, she died in her sleep, from respiratory arrest, leaving behind a six-year-old son. Her mother, Marianne Skolek Perez, was a nurse.
.. Robin Hogen .. had launched a vigorous campaign to defend the drug, warning newspapers to be careful about their coverage
.. He had also enlisted Rudolph Giuliani, the former mayor of New York, and his associate Bernard Kerik to preëmpt any government crackdown.
.. “We have to be politically Machiavellian, often, to win the day,”
.. Purdue’s senior medical adviser, J. David Haddox, who insisted that OxyContin was not addictive. He once likened the drug to a vegetable, saying, “If I gave you a stalk of celery and you ate that, it would be healthy. But if you put it in a blender and tried to shoot it into your veins, it would not be good.”
.. it was Purdue’s position that OxyContin overdoses were a matter of individual responsibility, rather than the drug’s addictive properties.
.. Howard Udell, Purdue’s general counsel, who had been a longtime legal adviser to the Sacklers
.. Udell was clearly aware, however, of the abuse potential of OxyContin. According to court documents, his own secretary became addicted to the drug, and was subsequently fired by Purdue.
.. for Purdue and the Sacklers, “there was a sense almost of betrayal—how could people put the availability of that product in jeopardy by abusing it for pleasure?”
.. the dangers of OxyContin were intrinsic to the drug—and Purdue knew it.
.. They could sleep through the night—a crucial improvement over conventional painkillers, such as morphine
.. Roughly half the women required more medication before the twelve-hour mark.
.. the claim of twelve-hour relief was an invaluable marketing tool. But prescribing a pill on a twelve-hour schedule when, for many patients, it works for only eight is a recipe for withdrawal, addiction, and abuse.
.. many people who were not drug abusers—and who took OxyContin exactly as their doctors instructed—began experiencing withdrawal symptoms between doses.
.. patients were coming to them with symptoms of withdrawal (itching, nausea, the shakes) and asking for more medication. Haddox had an answer. In a 1989 paper, he had coined the term “pseudo-addiction.” As a pain-management pamphlet distributed by Purdue explained, pseudo-addiction “seems similar to addiction, but is due to unrelieved pain.”
.. Pseudo-addiction generally stopped once the pain was relieved—“often through an increase in opioid dose.”
.. though Sackler presided over the tremendously successful launch of OxyContin, he has never given an on-the-record interview about the drug.
.. Purdue refused to concede that it posed risks. Company leaders worried mainly that attempts to stem overdoses might deprive pain patients of access to the drug.
.. it had maintained a contract with I.M.S., a little-known company, co-founded by Arthur Sackler, that furnished its clients with fine-grained information about the prescribing habits of individual doctors. Purdue’s sales representatives used the data to figure out which doctors to target.
.. “They know exactly what people are prescribing,” Kolodny said. “They know when a doctor is running a pill mill.”
.. James Greenwood, a Pennsylvania congressman, asked Friedman whether Purdue would take any action if, say, I.M.S. data revealed that a rural osteopath was writing thousands of prescriptions.
Friedman replied that it was not up to Purdue to assess “how well a physician practices medicine.”
.. overprescribing generated tremendous revenue for the company.
.. such prescribers were given a name that Las Vegas casinos reserve for their most prized gamblers: whales.
.. in 2004 Blumenthal filed a complaint against Purdue, on behalf of the State of Connecticut.
.. If OxyContin was being widely prescribed at intervals of fewer than twelve hours, the company might lose its “two pills a day” marketplace advantage against cheaper alternatives, like generic morphine, and insurers could start refusing to cover the costs.
.. “These pronouncements about how safe the drug was emanated from the marketing department, not the scientific department. It was pretty shocking. They just made this stuff up.”
.. In 2006, Purdue settled with Hanly’s clients, for seventy-five million dollars
.. Rudolph Giuliani had tried, on Purdue’s behalf, to get the lead prosecutor to scuttle the case.
.. Arlen Specter, the Republican senator from Pennsylvania, remarked that such fines amounted to “expensive licenses for criminal misconduct.”
.. one of his fixations was the unethical behavior of tobacco companies.
.. the tobacco companies had more money to spare than Purdue does. “To resolve the opioid problem, you’re going to need billions,” he said. “Treatment alone could be fifty billion dollars or more. And you need prevention and education programs on top of that.”
.. Prescriptions are expensive, and taxpayers often foot the bill, through programs like Medicaid. Then, as the ruinous consequences of opioid addiction take hold, the public must pay again—this time for emergency services, addiction treatment, and the like. Moore feels that the Sackler family, as the initial author and a prime beneficiary of the epidemic, should be publicly shamed.
.. They duped the F.D.A., saying it lasted twelve hours. They lied about the addictive properties. And they did all this to grow the opioid market, to make it O.K. to jump in the water.
.. Purdue fought the suit with its customary rigor, pushing to move the proceedings elsewhere, on the ground that the company could not get a fair trial in Pike County, Kentucky—the rural stretch of coal country where the state intended to try the case.
.. The report was revealing in ways that Purdue may not have intended: according to the filing, twenty-nine per cent of the county’s residents said that they or their family members knew someone who had died from using OxyContin. Seven out of ten respondents described OxyContin’s effect on their community as “devastating.”
.. Sackler’s demeanor during the session reminded him of Jeremy Irons’s portrayal of Claus von Bülow, the aristocrat accused of murdering his wife, in the 1990 bio-pic “Reversal of Fortune.” “A smirk and a so-what attitude—an absolute lack of remorse,”
.. the 1997 Pikeville High School football team. “Nearly half the players had died of overdoses, or were addicted,” he said. “It was going to be a pretty good visual.”
.. Purdue has sometimes claimed to have never “lost a case” related to OxyContin, but it’s more accurate to say that the company has never allowed a case to go to trial, often settling rather than litigating the culpability of the company—and the Sacklers—in open court.
.. the main reason these folks don’t go to trial,” Denham said. “Because all these documents could end up in the public record.” The Kentucky prosecutors were required to destroy millions of documents, or return them to Purdue.
.. The idea that they’re fighting so hard to keep this deposition hidden should tell you something.
.. These were urbane, expensively educated, presumably well-informed people. Could they conceivably be unaware of the accumulated evidence about the tainted origins of their fortune?
.. Someone who knows Mortimer, Jr., socially told me, “I think for him, most of the time, he’s just saying, ‘Wow, we’re really rich. It’s fucking cool. I don’t really want to think that much about the other side of things.’ ”
.. I wondered whether philanthropy might represent, for at least some of the Sacklers, a form of atonement. But, when you consider the breadth of the family’s donations, one field is conspicuously lacking: addiction treatment, or any other measures that might serve to counter the opioid epidemic.
.. companies often make a minor tweak to a branded product shortly before the patent expires, in order to obtain a new patent and reset the clock on their exclusive right to produce the drug. The patent for the original OxyContin was set to expire in 2013.
.. Purdue had long denied that the original OxyContin was especially prone to abuse. But, upon receiving its patents for the reformulated drug, the company filed papers with the F.D.A., asking the agency to refuse to accept generic versions of the original formulation—because they were unsafe.
.. Younger people, who can less readily secure prescriptions for pain—and for whom OxyContin may be too expensive—have increasingly turned to black-market substitutes, including heroin.
.. “How the Reformulation of OxyContin Ignited the Heroin Epidemic.” A survey of two hundred and forty-four people who entered treatment for OxyContin abuse after the reformulation found that a third had switched to other drugs. Seventy per cent of that group had turned to heroin.
.. Purdue pinpointed “communities where there is a lot of poverty and a lack of education and opportunity,” adding, “They were looking at numbers that showed these people have work-related injuries, they go to the doctor more often, they get treatment for pain.”
The Xalisco boys offered potential customers free samples of their product. So did Purdue.
.. Purdue likes to emphasize that there are many other powerful painkillers, and that OxyContin never had more than two per cent of the market for opioids
.. But most painkillers are prescribed for very short periods—following surgery, for instance—and in relatively small doses, whereas OxyContin’s sales have been driven by long-term, high-dose prescriptions
.. If one measured market share by the actual volume of narcotics administered, OxyContin’s would be considerably higher. Some doctors I spoke with estimated that it could be as high as thirty per cent.
.. Purdue acknowledged that even patients “who take OxyContin in accordance with its F.D.A.-approved labeling instructions will likely develop physical dependence.”
.. It may also be that OxyContin has achieved market saturation.
.. Last year, in Ohio, a state particularly hard hit by the epidemic, 2.3 million residents—roughly one in five people in the state—received a prescription for opioids.
.. “Opioids really do afford pain relief—initially,” he said. “But that relief tends to diminish over time. That’s, in part, why people increase the dose. They are chasing pain relief from a drug that has failed.
.. The Sackler family and Purdue Pharma could have taken responsibility in a similar spirit: apologizing for their role in unleashing a national catastrophe while noting that, during the nineties, they had relied on a series of mistaken assumptions about the safety of OxyContin. But Purdue has continued to fight aggressively against any measures that might limit the distribution of OxyContin, in a way that calls to mind the gun lobby’s resistance to firearm regulations.
Confronted with the prospect of modest, commonsense measures that might in any way impinge on the prescribing of painkillers, Purdue and its various allies have responded with alarm, suggesting that such steps will deny law-abiding pain patients access to medicine they desperately need. Mark Sullivan, a psychiatrist at the University of Washington, distilled the argument of Purdue: “Our product isn’t dangerous—it’s people who are dangerous.”
.. after Purdue made its guilty plea, in 2007, it assembled an army of lobbyists to fight any legislative actions that might encroach on its business. Between 2006 and 2015, Purdue and other painkiller producers, along with their associated nonprofits, spent nearly nine hundred million dollars on lobbying and political contributions—eight times what the gun lobby spent during that period.
.. Since Purdue made it more difficult to grind OxyContin pills, prescriptions have reportedly plummeted by forty per cent. This suggests that nearly half of the original drug’s consumers may have been crushing it to get high.
.. In August, 2015, over objections from critics, the company received F.D.A. approval to market OxyContin to children as young as eleven.
.. the Sacklers continue to receive some seven hundred million dollars a year
.. the real future of OxyContin may be global
.. But the Sackler family has only increased its efforts abroad, and is now pushing the drug, through a Purdue-related company called Mundipharma, into Asia, Latin America, and the Middle East
.. Part of Purdue’s strategy from the beginning has been to create a market for OxyContin—to instill a perceived need by making bold claims about the existence of large numbers of people suffering from untreated chronic pain.
.. Mundipharma commissioned studies showing that millions of people in these countries suffered from chronic pain.
.. In Mexico, Mundipharma has asserted that twenty-eight million people—a quarter of the population—suffer from chronic pain.
.. In China, the company has distributed cartoon videos about using opioids for pain relief; other promotional literature cites the erroneous claim that rates of addiction are negligible.
.. The term “opiophobia” has largely fallen into disuse in America, for obvious reasons. Mundipharma executives still use it abroad.
.. “It’s a parallel to what the tobacco industry did,” Mike Moore told me. “They got caught in America, they saw their market share decline, so they export it to places with even fewer regulations than we have.
.. Yale, announced that the university will rename a residential college that was named for John C. Calhoun, because Calhoun’s “legacy as a white supremacist and a national leader who passionately promoted slavery as a ‘positive good’ fundamentally conflicts with Yale’s mission and values.”
.. in the time it likely took you to read this article six Americans have fatally overdosed on opioids.
.. “A truly philanthropic family, looking at the last twenty years, would say, ‘You know, there’s several million Americans who are addicted, directly or indirectly, because of us.’ Real philanthropy would be to contribute money to taking care of them.
.. adding their name to a building—it rings hollow. It’s not philanthropy. It’s just a glorification of the Sackler family.”
.. more than two and a half million Americans have an opioid-use disorder.
.. “If the Sacklers wanted to clear their name, they could take a very substantial fraction of that fortune and create a mechanism for providing free treatment for everyone who’s become addicted.”
.. Alfred Nobel, the inventor of dynamite, created the Nobel Peace Prize.
.. the descendants of John D. Rockefeller have devoted resources to addressing climate change and critiquing the environmental record of the oil company he founded
..tobacco-company C.E.O.s: “We asked them, ‘What do you want?’ And they said, ‘We want to be able to go to cocktail parties and not have people come up and ask us why we’re killing people.’
.. An addicted baby is now born every half hour.
.. In places like Huntington, West Virginia, ten per cent of newborns are dependent on opioids.