by John Temple
Another thing about opioids: Nerve cells become desensitized to them more quickly than any other group of drugs. Higher and higher doses are necessary to produce the same impact.
They’re also addictive. Severely. Profoundly. And quickly. Withdrawal symptoms can be detected at the cellular level after a single dose of morphine. Administer opioids long enough, and the patient will become physically and psychologically dependent, terrified that the supply will be cut off, willing to go great lengths to forestall the nibbling panic of early withdrawal. That dread is felt more frequently as the body builds a tolerance to the drug, always needing more. Long-term users become physically dependent. Addicts go a step further and crave the drug psychologically, love the euphoria and seek more of it.
American doctors have known about the dark side of opioids for a long time, at least since hundreds of thousands of Civil War veterans became morphine addicts after that drug was administered liberally to wounded soldiers. Around the turn of the previous century, opium and other narcotics were available in a number of snake-oil elixirs, including baby-soothing formulas. Over time, the medical establishment came to the firm conclusion that heavy-duty narcotics were best prescribed sparingly, to patients in such bad shape that the risk of addiction seemed a laughably minor menace, such as cancer patients with tumors gnawing at their bones, or to someone in agony in a controlled, hospital environment. Almost by definition, opioids were not considered to be acceptable treatments for long-term chronic pain, because long-term use meant dependence. Doctors generally agreed you didn’t simply send people home with a big supply of the stuff and hope for the best.
It was often hard to tell who was in pain. Pain is personal, subjective. It is influenced by mood, psychology, upbringing. It’s cultural too. The Irish were less likely to voice pain than the Italians, according to a 1950s study at a veterans hospital in San Francisco. Pain had a randomness, an arbitrary nature that didn’t sit well with doctors, who were, after all, scientists looking for something to measure.
Over the decades, pharmaceutical companies developed and released an ever-expanding lineup of narcotics of different strains and mixtures and strengths. Vicodin, a mix of hydrocodone and acetaminophen. Percocet, oxycodone and acetaminophen. Fentanyl, usually administered through a skin patch. MS Contin, a long-acting morphine formulation. Sometimes researchers thought they’d found one that didn’t get you high, but there was an army of junkie scientists out there who would burn and dissolve and combine until they unlocked the narcotic trove. Then word would get around. Mix pentazocine with this drugstore antihistamine and you’ve got yourself a nice speedball. Or take a time-release morphine tablet, painstakingly peel off the outer coating, then crush, dissolve, and inject. There was always a way.
So the pharmaceutical companies kept the dosages small and typically cut their products with acetaminophen or aspirin, which discouraged addicts from ingesting massive doses. And doctors were trained to regard painkillers as a last resort. Which meant that many patients lived in pain. Too many, according to a new generation of doctors that began to emerge in the 1980s. Pain management specialists saw patients in agony, desperate for a cure and often unable to get medicine that would give them relief. Pain was real, they said, and it was destroying lives. These specialists began to wonder if physicians had become too reluctant to use the painkilling power of opioids.
By the early 1990s, as some doctors were reconsidering their approach to pain, a smallish, family-owned pharmaceutical company called Purdue Pharma was looking for ways to grow its customer base. Purdue was best known for an extended-release morphine drug called MS Contin. Unlike traditional morphine, which wore off within a few hours, these pills dissolved slowly and allowed cancer patients to sleep through the night. But Purdue’s patent on the formulation would expire soon, which meant that cheaper generic versions would soon be eating into its market share. The company was developing a new drug, an oxycodone pill it would call OxyContin.
Like MS Contin, OxyContin was a controlled-release pill. Swallowed, the dose broke down slowly in the digestive system, doling itself out over twelve hours. This meant Purdue could pack much more oxyco-done into each pill. Percocets contained doses of 5 or 10 milligrams of oxycodone. By contrast, OxyContin came in doses of 10 milligrams, 15 milligrams, 20 milligrams, 30 milligrams, 40 milligrams, 80 milligrams, and even the whopping 160-milligram horse pill, a midnight-blue oblong pebble nearly an inch long. The other thing was that OxyContin was pure. It wasn’t cut with acetaminophen or aspirin. The only active ingredient in the pill was oxycodone.
Purdue didn’t want simply to provide an alternative to MS Contin. That drug was used primarily to ease the suffering of cancer patients, a limited pool of consumers who typically either died or got better. Purdue wanted OxyContin to be prescribed to a much broader array of patients and for a longer period of time. The untapped marketplace was chronic pain, which could mean anything from backaches to arthritis to the crippling agony of trigeminal neuralgia. If Purdue could persuade a portion of that vast and varied market to take OxyContin, the drug would be a blockbuster.
To accomplish this, Purdue had to do no less than undertake a massive, multi-pronged hearts-and-minds campaign to change the way American doctors and the public felt about prescription narcotics. The company needed to train people to think of opioids as benign liberators, as long as they came in pill form and with a prescription.
Purdue leaders borrowed a page from the advertising industry: problem-solution marketing. They would market and publicize the problem of untreated pain. Then they’d promote the solution: OxyContin.
Over the following decade, Purdue Pharma created or funded a vast network of mouthpieces to promote and justify the use of heavy-duty narcotics to ease all kinds of pain. The company’s primary hurdle was to convince prescribers that their pain patients would not become addicted to OxyContin, even if they took heavy doses of it for a long period of time. This was no easy task, since it directly contradicted thousands of years of human experience with opiates.
The company found and cultivated “key opinion leaders,” usually doctors who were already promoting the idea that pain was undertreated and that narcotics should be more liberally prescribed. Researchers like Dr. J. David Haddox, who helped coin the term “pseudoaddiction.” Pseudoaddicts, Haddox said, were pain patients who displayed common drug-seeking behaviors: demanding specific drugs, hoarding drugs, seeking early refills, taking higher doses than prescribed. Pseudoaddiction looked a lot like addiction, Haddox said, but it wasn’t addiction. Those patients simply needed more pills. The counterintuitive concept was based on a case study of a single cancer patient, and it hadn’t been backed up by rigorous studies. Nevertheless, Purdue seized upon the new word—pseudoaddiction—and liberally sprinkled it throughout educational materials. The company also hired Haddox and made him a top executive.
Purdue poured millions of dollars into organizations like the American Academy of Pain Medicine, the American Pain Society, and the American Pain Foundation, and those organizations backed or promoted the work of pro-opioid researchers. Some researchers dug up obscure and largely inapplicable nuggets of scientific data that seemed to support a pro-opioid hypothesis, then published and republished that data. One Purdue-funded study claimed that “psychological dependence or addiction is low” for chronic pain patients on narcotics. The Purdue study cited a single article from the prestigious New England Journal of Medicine. It didn’t mention that the “article” was a letter to the editor, published in 1980, and that its conclusions were based on a simple review of the charts of hospitalized patients, not a scientific study of long-term narcotic use.
But the idea was out there, published in a scientific journal: Fewer than 1 percent of pain patients would develop addictions.
Armed with this seemingly legitimate number, Purdue got to work.
Suddenly, in the late 1990s, news stories about pain began to appear. Profiles of chronic pain sufferers who couldn’t get n
arcotic prescriptions due to doctors’ fears of addiction. Trend pieces about the prevalence of pain and its undertreatment. Purdue officials themselves were rarely mentioned, but the stories were peppered with quotes from Purdue-backed consultants and researchers and doctors. The stories created the general impression that tens of millions of Americans were suffering in needless pain.
Many of the stories were planted by groups like the American Pain Foundation. The foundation claimed to be a patient advocacy organization, but 90 percent of its money came from the drug industry, including big grants from Purdue. The foundation acted as a front for Purdue and other drugmakers, advancing pro-opioid policies in ways that the companies themselves could not. The foundation funded pain management web talk shows, published policy guides that plugged narcotics, and marshaled pain patients to send angry e-mails to reporters, prompting news stories about the stigma they had faced when seeking medication. It was a smart move, Golbom believed, because it created the impression that anyone who questioned the escalating use of prescription narcotics lacked empathy for people in pain. Only a heartless clod wanted to deny people in pain the medications they said they couldn’t live without.
Similar stories originated from new “grassroots” regional pain advocacy organizations that had sprung up, such as the Appalachian Pain Foundation, based in Huntington, West Virginia, which received a $20,000 grant from Purdue shortly after it formed in 2000.* The foundation arranged a series of meetings in Kentucky and West Virginia to spread the word among local doctors that opioids were underutilized even in their pill-swamped communities. The doctor who co-chaired the foundation said the Purdue grant had no effect on the foundation’s work. Years later, he lost his medical license after airport officials found oxyco-done and hydrocodone bottles with other people’s names on them among his luggage. A subsequent investigation revealed that a number of his patients had died of overdoses.
Purdue targeted the doctors who controlled the prescription pads. Most physicians had received maybe an hour or two of pain management training way back in med school. They needed a re-education in painkillers, and Purdue supplied it with the largest narcotics marketing campaign ever. Between 1996 and 2002, Purdue funded more than twenty thousand pain-related educational programs, almost ten a day, seven days a week. During the same years, Purdue conducted more than forty national pain management training conferences at resorts in Boca Raton and Scottsdale, paying the travel costs for more than five thousand physicians who attended. More than twenty-five hundred physicians were on Purdue’s speaker bureau list. They went home with plush toys, fishing hats, CDs, and pens, all branded with the OxyContin logo. A favorite freebie was the heat-sensitive Oxy-Contin mug that bore the words: “The one to start with . . . .” When filled with hot coffee, the rest of the slogan materialized: “The one to stay with.”
The educational seminars made the most of the unfounded statistic that “fewer than one percent” of patients would develop addictions. One continuing medical education program sponsored by Purdue promoted opioid therapy as the only solution for chronic conditions such as back pain. The program contained a role-playing exercise in which a patient admits he is taking twice as many pills as he’s supposed to. An authoritative narrator cautions the doctor not to jump to the conclusion that the patient is addicted, even if he seems desperate. The role play ends with the doctor prescribing a high-dose opioid.
Purdue doubled its sales force during those years, from 318 to 767 pharmaceutical reps. In the trade, the reps are called detailers, and they’re typically good-looking, gregarious, and well-dressed. They remember the names of the clinic receptionists and secretaries and nurses. Purdue expected each drug rep to develop a list of 105 to 140 physicians within a specific sales region and call each one every three or four weeks. And they didn’t target only oncologists and pain management specialists. They went after family doctors and general practitioners, a broader and less painkiller-savvy prescriber. Purdue paid its reps better than most drug-makers paid theirs—by 2001, an average salary of $55,000 and an average bonus of $71,500. Purdue spent a half-billion dollars on the one-on-one sales strategy between 1996 and 2001.
Purdue drug reps also had another tool: OxyContin coupons. Free samples were a common way to promote a new medication, but the DEA didn’t allow it with controlled substances like OxyContin. So in 1998 and 1999, Purdue bypassed this rule by giving each rep twenty-five coupons for a free thirty-day supply of the drug. In 2000 and 2001, as OxyContin’s reputation grew, the company cut the free trials to seven days. Reps gave the coupons to doctors, who passed them on to patients. The freebies cost Purdue $4 million a year, but in the narcotics business, it was a good long-term strategy.
Purdue drilled its reps on two selling points. One, OxyContin was the first narcotic that wouldn’t hook patients. And two, fewer than 1 percent of pain-management patients get addicted anyway.
Purdue’s army of drug reps reminded Golbom of the salesmen a century earlier who peddled patent medicines like Hamlin’s Wizard Oil or Hostetter’s Celebrated Stomach Bitters, men who assured their customers that a bottle of snake oil would cure everything from arthritis to kidney disease.
The heart-and-minds campaign worked, beyond even Purdue’s expectations. Within a few years, OxyContin became a major pharmaceutical hit, one of the top-twenty brand-name medications in the United States. By 2002, six years after its release, Purdue was selling almost $1.5 billion of the drug each year—eight times the volume the company had projected. The single drug represented 80 percent of Purdue’s net sales. It was the biggest-selling brand-name controlled substance on the market.
The once sleepy drugmaker was now a powerhouse, and it wasn’t about to concede that its star product had a major flaw.
OxyContin’s warning label instructed users not to crush or dissolve the pills because the entire narcotic load would be released at once. In other words, do not powderize the pill . . . unless you want to get ecstatically, euphorically high. Abusers paid attention and realized how ridiculously easy it was to beat the pill’s timed-release formulation. Just crush it, and they’d get the whole thing at once. They could wrap it in foil and grind it between their molars, or take a hammer to it. Still, after ingesting it that way for a time, the knife-edge of joy became just a bit blunted. So abusers would try snorting it to get it to the bloodstream faster, boost the rush. And when that dulled, they could mix the powder with water, draw it into a needle, and shoot it straight into the vessel.
People began dying with OxyContin in their bloodstreams. At first, around the year 2000, the overdose reports were haphazard and anecdotal, a few dozen deaths tallied by a worried medical examiner in Virginia or a few hundred reported by a DEA researcher. News reports detailed a wave of OxyContin abuse that originated in rural areas with a tradition of pill dependency, such as western Virginia, eastern Maine, and Kentucky.
Purdue pushed back against the evidence. Just because oxycodone was found in a corpse’s bloodstream didn’t mean it came from an Oxy-Contin pill, company spokesmen said. And if there were other drugs or alcohol involved, as was often the case, how could you definitively blame oxycodone?
But deaths involving prescription narcotics continued to mount, until the trend was impossible to dismiss. Overdose deaths involving prescription opioids quadrupled between 1999 and 2007, from about three thousand to twelve thousand per year. By contrast, cocaine killed about six thousand users in 2007, heroin about two thousand. Prescription narcotics were now killing more Americans than all illegal drugs combined.
In fact, while the heroin years of the 1970s and the crack crisis of the 1980s had produced a frenzy of publicity, those outbreaks had barely nudged the overall drug death rate. The unintentional drug overdose death rate had hovered between one and two annual deaths per one hundred thousand citizens during the heydays of those drugs. By 2007, the overdose rate had shot up to about nine deaths per one hundred thousand, almost entirely due to opioid-related deaths. Pills were far deadli
er than crack or heroin, but they didn’t create the same national hysteria.
There was a reason for this lack of outrage. Golbom noticed that almost every story about the increasing devastation quoted a pain management doctor or “expert” from one of the industry fronts like the American Pain Foundation. There was always a paragraph about the “undertreatment of pain,” with the implication that even more opioids were needed to solve the problem. Purdue had created a truth, backed up by a body of seemingly legitimate research and publication, and few seemed to question the underlying premise that OxyContin was an effective drug for chronic pain, safe “when taken as prescribed.”
It took Golbom time to fully comprehend the implications of Purdue’s strategy, but once he did, he realized its brilliance. The company was selling an addictive drug that it said would not addict you as long as it was taken as prescribed. Then, when the drug did addict someone, and they began taking too much of it, or hoarding it to take all at once, or trying to obtain multiple prescriptions or early refills—then, that person was no longer taking it as prescribed. That person became one of the outcasts, an addict, and therefore the “safe when taken as prescribed” dictum remained valid. Purdue seemed to regard those folks as a tragedy of their own making. But the company affirmed that its responsibility was not to addicts who were abusing the drug, but to the untold millions of pain sufferers who needed it.
Golbom wondered how many addicts had begun taking OxyContin under the care of a doctor. He came to realize that there was very little difference between heroin and opioid narcotics. Heroin had been stigmatized as a bottom-of-the-barrel drug, the destination of the dirtiest of street junkies. Whereas, “pain pills” had been systematically sanitized in the public’s mind. Even in the flood of news stories about oxycodone deaths, reporters and experts referred to prescription narcotics as if they were, at worst, a gateway to the hard stuff. As a pharmacist, Golbom could determine only two clear advantages OxyContin had over heroin as a recreational drug. One, OxyContin was legal. Two, it was pharmaceutical-grade—you knew exactly what was in it, unlike a bag of heroin bought on the street. Other than that, oxycodone addiction and heroin addiction were the same thing.