—
IN LATE 1995, at the same time that Russell Portenoy was urging American physicians to get over their fear of painkillers, the FDA approved Purdue Pharma’s timed-released version of OxyContin. Purdue’s sales force promoted the drug for the treatment of lower back pain, arthritis, trauma, fibromyalgia, dental procedures, broken bones, sports injuries, and pain resulting from surgery. In other words: everything. And they constantly repeated Portenoy’s mantra that less than one percent of patients would become addicted to the drug.
In 1996, more than 300,000 prescriptions for OxyContin were written for a net profit to Purdue Pharma of $44 million. Realizing it had created the right drug at the right time, Purdue doubled its sales force, offered coupons for a free 7- to 30-day supply of the drug (34,000 coupons were redeemed), increased its yearly advertising budget to $200 million, and paid $40 million in incentive bonuses. In 2001, Purdue reaped $1.45 billion from the sale of OxyContin, the highest retail sale of any named pharmaceutical product, including Viagra.
—
SALES OF OXYCONTIN also benefited from a vigorous black market.
More than 70 percent of recreational OxyContin users had procured the drug from friends or relatives; 5 percent from drug dealers on the Internet. Sometimes users stole the drug from pharmacies; 90 percent of robberies in Pulaski, Virginia, were due to OxyContin abuse, and half of the inmates in Hazard, Kentucky, were incarcerated for OxyContin-related crimes. Sometimes, to supplement their meager Social Security checks, the elderly poor used Medicare or Medicaid to acquire a bottle of a hundred 80-milligram tablets of OxyContin and sold them on the street for $1.00 per milligram, netting an $8,000 profit for the seller. Teenagers stole OxyContin from their parents. (One street name for OxyContin was “kiddie dope.”) Prescriptions were forged. Women turned to prostitution to feed their habit. Pharmacists diverted the drug and sold it on the side. Before he was arrested, one Pennsylvania pharmacist had illegally sold hundreds of thousands of dollars worth of prescription painkillers, mainly OxyContin, over a three-year period, netting him $900,000 (which he later lost in the stock market).
Doctors took advantage of the OxyContin gold rush, selling prescriptions for money or sex. Dr. Randolph W. Lievertz of Indianapolis wrote more than $1 million in prescriptions paid for by the state’s Medicaid program; $130,000 of that total was written for one female patient who was part of a drug ring that sold OxyContin on the street. To honor the prescription, the woman would have had to ingest 31 tablets every 12 hours instead of the one tablet recommended by the manufacturer. Lievertz wasn’t alone. Pill mills sprang up across the country. One eastern Kentucky doctor saw 150 patients a day, writing prescriptions for painkillers after spending less than three minutes with each patient. Florida alone was home to hundreds of these facilities.
Doctors were arrested and charged with manslaughter and murder. Some were jailed. No case, however, drew more national media attention than that of Dr. James Graves, a 55-year-old Florida physician who was charged with manslaughter in the overdose deaths of four of his patients. Graves’s prescription mill was widely known among addicts. “The word spread that he was the go-to doctor to get pills,” said Russ Edgar, the assistant state attorney. Edgar argued in court that Graves had bragged that writing prescriptions for painkillers was a “gold mine” because he had rarely examined patients and didn’t have to fill out medical records. Edgar also claimed that Graves had ignored the pleas of pharmacists and parents to change his prescribing habits. Indeed, Graves’s parking lot often resembled scenes more commonly found at sporting events. Patients would eat, work on their cars, and give each other high-fives when they emerged with their OxyContin prescriptions. “You’ve got to realize something’s wrong when outside your office people are having tailgate parties,” said Edgar.
During the trial, Edgar argued that, “Mother after mother after mother called the defendant’s office and asked him to quit giving their children drugs or they would die. The defendant did not quit and they continued to overdose.” Graves countered that no one would have died if patients had simply used the drugs as prescribed. And he railed against the prosecutor, whom he considered ungodly, telling the judge, “I pray to God something will change and somehow he will come to know Christ.” James Graves was sentenced to 63 years in prison for manslaughter. He was the first physician to be found guilty of manslaughter or murder in connection with the irresponsible prescribing of a painkiller.
—
NO AREAS SUFFERED THE NIGHTMARE of OxyContin pill mills more than rural Appalachia and the Ohio Valley.
OxyContin abuse first surfaced in rural Maine in the late 1990s, then spread down the East Coast to include West Virginia, Kentucky, and southern Ohio. (Another name for OxyContin was “hillbilly heroin.”) From 1995 to 2001, the number of patients treated for oxycodone abuse in Maine increased 460 percent, and in eastern Kentucky, 500 percent. In West Virginia, six new drug treatment clinics treated more than 3,000 addicts. Southwestern Virginia opened its first drug treatment center in 2000; within three years more than 1,400 patients were being treated; by 2003, the region had experienced an 830 percent increase in deaths from oxycodone abuse. By 1999, deaths from oxycodone use in Allegheny County in western Pennsylvania outnumbered car fatalities.
Appalachian emergency department physicians became experts in recognizing the symptoms of drug withdrawal, which included anxiety, runny nose, sweating, yawning, insomnia, loss of appetite, gooseflesh (the source of the phrase “going cold turkey”), back pain, abdominal pain, tremors, and occasional involuntary thrusting of the legs (the source of the phrase “kicking the habit.”)
—
IN 2003, 17 YEARS AFTER Russell Portenoy published his paper claiming that long-term use of oxycodone was relatively harmless and nonaddictive, Jane Ballantyne published a paper in the New England Journal of Medicine claiming exactly the opposite. Ballantyne showed that long-term use of drugs like OxyContin induced tolerance (larger and larger doses of the drug were required to induce the same effect), hyperesthesia (pain experienced while using painkillers was actually worse than the original pain), hormonal changes (specifically, a decline in production of cortisol, an important regulatory hormone), changes in the immune system, and a reduction in fertility, libido, and sex drive. Ballantyne concluded, “Whereas it was previously thought that unlimited dose escalation was at least safe, evidence now suggests that prolonged, high-dose opioid therapy may be neither safe nor effective.”
Ballantyne’s paper wasn’t news to the FDA, which had already changed the label on OxyContin. No longer did the label state that the timed-release formulation made it less likely for abuse; now it stated that the formulation made it more likely for abuse, addiction, overdose, and death. The warning wasn’t written in fine print; rather, the FDA issued its most strident alert—the so-called “black box” warning.
But it was too little, too late.
In 2002, a survey at a rural Michigan high school showed that 98 percent of students had heard of OxyContin and 9.5 percent had tried it; of those who had tried it, 50 percent had taken it more than 20 times. By April, 1,300 deaths caused by OxyContin had been reported to the FDA; in most cases, doctors had prescribed the drug. By the end of 2002, Purdue Pharma was selling more than $30 million worth of OxyContin every week, and sales had exceeded more than $2 billion a year.
In 2003, Rush Limbaugh, a conservative radio commentator who often railed against drug abusers for being morally bankrupt, admitted that he was addicted to OxyContin.
In 2004, three million people were using OxyContin—now the most prevalent prescription painkiller in the United States.
In 2007, 14,000 people died from overdoses of prescription painkillers, and health care and criminal justice system costs exceeded $55 billion.
In 2008, 15,000 people died from prescription painkillers—the leading cause of accidental death in 30 states.
In 2009, health insurers spent $72 billion in direct health care costs rel
ated to prescription painkillers.
By 2010, 22 million people had misused prescription painkillers, and more people had died from these drugs than from heroin and cocaine combined. Enough painkillers were now being prescribed to medicate every adult living in the United States around the clock for a month.
In 2012, 12 million Americans aged 12 and older reported the recreational use of prescription painkillers; 16,000 of those users died from overdoses. Painkillers were now the most widely prescribed class of drugs in the United States; every 19 minutes someone died from an overdose. (OxyContin overdoses were indistinguishable from overdoses of opium, morphine, or heroin, all of which suppress the rate and depth of respiration. Patients breathe as few as four times a minute; blood pressure begins to drop, body temperature falls, and the skin becomes cold and clammy. Because the brain isn’t getting enough oxygen, the patient seizes and eventually dies from respiratory failure.)
In 2014, U.S. retail pharmacies dispensed 245 million prescriptions for opioid pain relievers. About 2.5 million adults were addicted to the drug.
Few insurance companies did much to discourage abuse. Before OxyContin burst onto the scene, chronic pain was treated with a combination of psychotherapy, biofeedback, exercise, and physical therapy. The goal was to leave the painkillers at the door. Although several studies had showed that this multidisciplinary approach to relieving pain worked just as well if not better than chronic drug use, the fact remained that the drugs were less expensive than the therapies. Unfortunately, many insurance companies encouraged the drugs. At best, this was shortsighted. Workers who took high doses of painkillers were out of work three times longer than those with similar injuries who took lower doses of the drugs.
—
ON MAY 10, 2007, Purdue Pharma, along with three company executives, pleaded guilty to one count of “misbranding” OxyContin. The court ruled that Purdue had minimized risks, made unsubstantiated claims, and failed to include clear warnings about how, under certain conditions, the drug could be fatal. Just as Bayer had continued to market heroin when it was evident that the drug was causing harm, Purdue had been slow to inform the public about the potential dangers of OxyContin. The three executives were fined $34.5 million (which Purdue paid), barred from working for any company that sold medical products for the next 12 years, and required to perform 400 hours of community service in drug-treatment centers. Purdue also paid an additional $634 million penalty. Many of the parents whose children had died from OxyContin were present during the sentencing. “Our children were not drug addicts; they were typical teenagers,” said one woman, whose 19-year-old son had died. “We’ve been given a life sentence.” Judge James P. Jones, who presided over the trial, said he would have liked to have sent company executives to prison, but was bound by the plea bargain.
—
IN AUGUST 2010, Purdue replaced their timed-release form of OxyContin with a “tamper-resistant” product. The new version formed a thick, sticky gel that made it more difficult to crush. Two years later, a study in the New England Journal of Medicine examined the impact of this new formulation. Researchers found that although OxyContin abuse had decreased, 24 percent of users had found a way to defeat the tamper-resistant properties and 66 percent had just switched to another drug, mainly heroin. Despite the reformulation, yearly sales of OxyContin still topped $2 billion.
—
IN 2012, Russell Portenoy, who had become chairman of pain medicine and palliative care at Beth Israel Medical Center in New York City, recanted: “I gave innumerable lectures in the late 1980s and ’90s about addiction that weren’t true,” he said. “We didn’t know then what we know now.” During the previous decade, more than 100,000 people had died from overdoses of painkillers. Steven Passik, a psychiatrist who had worked closely with Portenoy, recalled the war on pain: “It had all the makings of a religious movement,” he said. “It had a kind of spirit to it.”
In the end, OxyContin was one of the most addictive narcotics ever sold. And Russell Portenoy’s war on pain was one of modern medicine’s biggest mistakes.
—
ON JANUARY 16, 2016, an article written by Gina Kolata and Sarah Cohen in the New York Times stated: “The rising death rates for young white adults make them the first generation since the Vietnam War years of the mid-1960s to experience higher death rates in early adulthood than the generation that preceded it.” Opioid overdoses were now the leading cause of accidental deaths in the United States.
On March 15, 2016, the Centers for Disease Control and Prevention (CDC) finally offered guidelines for the sensible use of prescription painkillers, stating that doctors should prescribe them: (1) only after nonprescription painkillers like ibuprofen and physical therapies had failed; (2) in quantities not to exceed a three-day supply for short-term pain and rarely longer than seven days (typically, patients are given two weeks or a month worth of pills); and (3) only when improvement was significant. The guidelines did not apply to patients who were receiving painkillers for cancer or end-of-life treatment. The American Academy of Pain Management—a group that receives funds from Purdue and Teva Pharmaceuticals—and the Washington Legal Foundation, which frequently represents pharmaceutical company interests in court, opposed the new guidelines. After all, painkillers were now a $9 billion a year industry. Robert Twillman, executive director of the academy, didn’t like the three- to seven-day dosing recommendation. “The numbers are still arbitrary,” he said. But Tom Frieden, director of the CDC, had had enough. “For the vast majority of patients with chronic pain,” he countered, “the known, serious, and far too often fatal risks far outweigh the transient benefits. We lose sight of the fact that prescription opioids are just as addictive as heroin.” Today, 80 percent of the world’s opioid prescriptions are written in the United States, even though only 5 percent of the world’s population lives there.
—
THE LESSON FROM THE ILL-FATED WAR on pain is a simple one: It’s all about the data. When Friedrich Sertürner feared that in morphine he had opened up a Pandora’s box and let loose a monster, his warnings were ignored. When Heinrich Dreser claimed that heroin was safe, he had only tested it on a handful of people for a few weeks. And when Russell Portenoy launched a national campaign promoting opioid use, he based his claims on 38 patients, 12 of whom had taken OxyContin. As Clara Peller said in her now iconic television commercial for Wendy’s hamburgers, “Where’s the beef?” If you’re going to medicate a nation, at the very least you should base your recommendations on a mountain of evidence, not a molehill.
CHAPTER 2
THE GREAT MARGARINE MISTAKE
“Avoid fried foods, which angry up the blood.”
—Satchel Paige
I grew up in Baltimore, Maryland. And although I know that you cannot go home again—that you can never recapture your youth—still, there were certain things that I had assumed would always be there.
For example, from the ages of 13 to 18, I was a Baltimore Colts season ticket holder. Every year, three friends (Jimmy, Jack, and Robert) and I would scrape up the $35 it took to buy a season ticket for the seven home games. On Sundays, we would take the bus down to Memorial Stadium: “the world’s largest outdoor insane asylum.” Baltimore loved their Colts. We couldn’t have supported them more. Then, with little warning, they were gone—off to Indianapolis in the middle of the night with their memorabilia crammed into the back of a Mayflower truck. Loyalty, apparently, could be a one-way street.
Another Baltimore staple were crabs from the Chesapeake Bay. During the summer we would go to a local crab house and crack crabs flavored with Old Bay Seasoning made by Baltimore’s own McCormick & Company. Then, due to overfishing, the crabs were gone. Now Baltimore’s crabs are flown up from Texas.
There was another tradition that I could always count on—something that won the “Best of Baltimore Award” in 2011 and has been featured on The View as well as the Food Network’s Rachael Ray and The Best Thing I Ever Ate. Something that eve
ry Baltimorean adores: Berger cookies.
Slathered with fudge over a modicum of shortbread, Berger cookies have been a Baltimore tradition since George and Henry Berger brought them over from Germany in 1835. Today, Berger cookies are made by a little bakery in the Cherry Hill section of Baltimore that, in 2012, had annual sales of $2.5 million, 98 percent of which was from Berger cookies. Amazing, when you consider that most of these cookies are distributed locally.
Unfortunately, like the Baltimore Colts and Chesapeake Bay crabs, Baltimore’s Berger cookies might also soon be a thing of the past. Unless the owner of the bakery, Charles DeBaufre, Jr., changes his recipe, the FDA will ban them. The reason: Berger cookies are made with partially hydrogenated vegetable oils, so they’re loaded with trans fats. DeBaufre has tried baking them with cooking oils and shortenings free of trans fats, without success. “We’ve tried it and trust me, it’s nasty,” he says. “The texture’s just not there. It’s an entirely different product.” If DeBaufre cannot come up with an alternative recipe soon, his cookie and his business will be gone.
—
THE THREAT TO BALTIMORE’S Berger cookies is explained by the most common reason that Americans die: heart disease, a phenomenon of the modern era. In the early 1900s, most people died from bacterial and viral infections. But, during the 20th century, advances like antibiotics, vaccines, safer drinking water, and purer foods have allowed us to live about 30 years longer—long enough to die from heart disease. To understand why, we first need to understand what makes the heart so vulnerable.
The heart is a muscle that, like any other muscle, needs the constant flow of blood, which supplies oxygen. Two major arteries, called coronary arteries, do this. If either of these arteries is blocked, then blood flow is disrupted, causing damage to the heart muscle and occasionally sudden death (that is, a heart attack). When researchers studied these blockages, they found cholesterol, a substance made by the body that is an essential component of cell membranes. They also found triglycerides, the main constituent of body fat. Doctors would eventually call the disease atherosclerosis, literally meaning “hardening of the arteries.”
Pandora's Lab Page 3