The opioid epidemic has devastated communities and lives across the country, causing more than 250,000 deadly overdoses between 1999 and 2016. It’s easy to point fingers, and there are plenty of places to point. But the epidemic didn’t begin with greedy drug companies or reckless prescribers. It began with compassionate doctors trying to end the suffering of millions of people in pain.
Since the new millennium, prescription painkillers, such as OxyContin, Vicodin and Percocet, have caused hundreds of thousands of drug overdoses. Illicit use of heroin and fentanyl has surged and devastated communities across the country. Doctors began prescribing drugs containing opiates at enormous rates in the late 1990s. After government crackdowns made the drugs harder to get, people addicted to the pills turned to a cheaper and more accessible alternative on the street. As a result, the number of people addicted to and overdosing from heroin increased significantly. These drugs aren’t new. Opium’s addictive and deadly potential has been known for centuries. Morphine addiction caused enough societal problems in the early 1900s that for more than 50 years American doctors rarely prescribed opiate-based drugs. They started changing their minds in the 1970s and ‘80s. Health care providers got tired of watching their patients live in pain. They didn’t want to watch burn victims agonize during tissue repair surgeries. They didn’t want to witness cancer patients suffer during their final days of life. For nearly a century, doctors searched for an alternative to opioids. When they couldn’t find one, they started changing how they treated patients receiving end-of-life care. Then a drug company introduced a product that changed the way pills worked. It led to a revolution that started with helping patients in chronic pain and led to scores of doctors prescribing highly addictive drugs to patients with minor ailments. It was about compassion. It was about ending suffering. Respected cancer specialists argued for a new approach to pain. Government agencies listened to their experts and jumped on board. Drug companies saw an opportunity to make money and added fuel to the fire.
“They had the impression people were still scared of opioids. They thought they were still fighting the tide. What happened was they took over and became a tidal wave.”
Marcia Meldrum, UCLA
“Almost all of these people had good intentions. They truly believed opioids could be used safely,” said Marcia Meldrum, associate researcher in the Department of Psychiatry and Biobehavioral Sciences at UCLA. “Throughout this era, all of these people, the pain management leaders and the government experts, they all had the impression that they had to keep talking about how safe opioid therapy was,” Meldrum told DrugRehab.com. “They had the impression people were still scared of opioids.
They thought they were still fighting the tide. What happened was they took over and became a tidal wave.” People were becoming addicted and dying from overdose deaths at increasing rates for years, but very few people noticed. When the first warning signs emerged, no one could predict the extent of the damage. “The scope of the problem only became clear in most areas when statisticians looked at the figures on overdoses and deaths,” Meldrum said. “Prior to that, in a sense, it was hidden.” Today, the pain management field is still in disagreement about the safety of opioid therapy. Law enforcement is shifting focus from local pill mills to online drug traffickers. The rehab industry is expanding efforts to combat widespread addiction to heroin and painkillers. Policymakers have only recently realized that overprescribing of opioids is at the root of the problem. “For years, the sole focus was on reducing non-medical use, reducing abuse,” Dr. Andrew Kolodny, co-founder of Physicians for Responsible Opioid Prescribing, told DrugRehab.com. “They were trying to stop kids from getting into grandma’s medicine cabinet. Nobody was asking ‘why does every grandma now have opioids in her medicine cabinet.’” The problem is complex because we can’t get rid of all opiate-based medications. If we did, what would happen to the 25 million adults in chronic pain or the millions of people who receive palliative care each year? Before opioids, those people suffered in pain.
“They were trying to stop kids from getting into grandma’s medicine cabinet. Nobody was asking ‘why does every grandma now have opioids in her medicine cabinet?’
Dr. Andrew Kolodny, Co-Founder, Physicians For Responsible Opioid Prescribing
An Era Of Pain
In the United States, we grow up using painkillers. Have a headache? Take an aspirin. Running a fever? Try some Tylenol. Sprain an ankle? Ice and ibuprofen. We get laughing gas when we have teeth pulled and powerful painkillers after surgery.
It wasn’t always like this. People suffered from pain for centuries without reliable sources of relief. Severe pain was once treated with alcohol, chloroform or a number of herbal remedies. For most of the 1900s, physicians treated severe pain with high doses of less effective pain relievers, such as aspirin, ibuprofen and acetaminophen. The drugs rarely worked.
A Brief History Of Opioids
Opium made its way to the United States around the time of the Revolutionary War, but its use was uncommon until morphine was synthesized from the plant in the early 1800s. During the Civil War, it was commonly used to treat soldiers. At that time, an estimated 400,000 soldiers treated for pain with morphine became addicted to opioids.
Some scholars believe that opioid use during the war was one of many significant factors that contributed to a sharp rise in opioid addiction in the late 1800s. “At one time in the 1800s, people could get opioids fairly freely,” Meldrum said. “They were available over the counter. They were available in the mail.” Near the end of the century, Bayer began selling heroin, a chemical derived from opium, for pain relief and cough suppression. Within one year, reports revealed that people were developing a tolerance to the drug. By 1910, Americans were crushing opioid pills and inhaling them for pleasure. Four years later, Congress passed the Harrison Narcotics Act, making opioids available only by prescription. “The original intent was not to limit the prescription of opioids for pain,” Meldrum said of the law. “It was to limit the recreational use of opioids, which had become a major problem in some areas of society. The Federal Bureau of Narcotics chose to essentially treat it as forbidding the prescription of opioids for almost any reason.”
During the 20th Century, physicians faced the challenge of balancing the treatment of pain with the risk of addiction. Most doctors believed that opioid painkillers should not be used, even in cancer patients with severe pain, until the final weeks of life. Only at that point, when no other treatment method was available, was it acceptable. “Between the 1920s and the 1950s, basically opioids are not prescribed for chronic pain,” Meldrum said. “They are prescribed for acute pain, for postoperative pain on a short-term scale. They are prescribed in the care of the dying.” Opioids didn’t disappear from health care, but doctors often preferred high doses of aspirin to treat pain, and that usually wasn’t effective. The American public knew of the dangers of opioid addiction. Many people in pain avoided opiate-based medications to avoid losing control of their minds, according to an article written by Meldrum in the Journal of the American Medical Association. She described how the story of Mrs. DuBose in the 1960 novel “To Kill a Mockingbird” exemplified that belief. The sickly character strove to taper off morphine before her death, and the other characters viewed her as brave for dying in pain but free of the drug’s influence.
Changing Opinions On Pain and Addiction
With such strong stigma associated with addiction and deep fears associated with opioids, doctors resorted to surgeries, nerve-blocking operations and other nonpharmaceutical methods to relieve chronic pain until the 1970s. In 1973, a former Army chief of anesthesiology named John Bonica helped lead the development of the International Association for the Study of Pain and the research journal Pain.
A plaque unveiled by the IASP commemorating the use of chloroform to study pain relief (Photo: gnomonic via Flickr)
“They had a big conference on cancer pain in Italy,” Meldrum said. “There were a number of researchers there from the hospice movement in Great Britain who had been using heroin fairly regularly for the treatment of dying patients. Their argument was that as long as you kept the dosage on a steady, controlled, minimal basis, you could safely medicate people for long periods of time with chronic opioid therapy.” The IASP led to the development of the American Pain Society — one of several pain societies that were developed in the ‘80s and ‘90s to advocate for pain relief. Meanwhile, oncologists at hospitals across the country, including the prestigious Memorial Sloan Kettering Cancer Center in New York City, were searching for nonaddictive treatments for cancer-related pain.
A Letter That Changed The Game
In the late 1970s, researchers from Boston Medical Center analyzed the medical records of hospitalized patients who had received narcotics. They found that of 11,882 patients who received narcotics, only four showed “reasonably well documented” symptoms of addiction and only one “major” instance of addiction. Jane Porter and Dr. Hershel Jick wrote a five-sentence letter to the editor in the New England Journal of Medicine describing the analysis in 1980. “We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction,” the authors wrote. The letter was not a peer-reviewed study, and it described only patients under doctor supervision in hospitals.
In an interview for the book “Dreamland: The True Tale of America’s Opioid Epidemic,” Jick told author Sam Quinones “If you read [the letter] carefully, it does not speak to the level of addiction in outpatients who take these drugs for chronic pain.” Quinones wrote that by the 1990s, Jick had forgotten about the letter. But the letter became one of the most prominent resources for pain-relief advocates who claimed that less than one percent of patients treated with opioids became addicted. It has been cited by more than 900 studies since it was published. Nurse Marsha Stanton told Quinones that she and other seminar speakers often cited it during the 1990s. “We all thought it was gospel,” she said.
“If you read [the letter] carefully, it does not speak to the level of addiction in outpatients who take these drugs for chronic pain.”
Dr. Hershel Jick, Boston University Medical Center
Developing The Argument For Pain Relief
Porter and Jick’s letter to the editor was one of several articles that contributed to changing opinions on opioid therapy for chronic pain. During the next decade, researchers laid the groundwork for drug companies to make aggressive and exaggerated claims about the safety and efficacy of opioids.
A survey of 151 burn facilities found that 22 out of more than 10,000 patients developed symptoms of addiction after receiving narcotics during a hospital stay, but each had a history of drug abuse. The researchers called for a re-evaluation of the use of pain relievers during debridement, a procedure in which damaged tissue is removed from the skin.
A study published in Pain found that of 38 patients treated for nonmalignant pain with opioids, only two developed symptoms of addiction. Both had histories of drug abuse, and the authors concluded that opioid therapy could be safe and effective for treating nonmalignant pain in patients with no history of substance abuse.
A review of the literature published in Scientific American titled “The Tragedy of Needless Pain” called Jick and Porter’s letter to the editor an “extensive study.” The author blamed unnecessary pain on society’s inability to distinguish “the emotionally impaired addict” with the “psychologically healthy pain sufferer.” He called on medical and government agencies to fund future studies to rescue people from pain.
Drs. Russell Portenoy and Kathleen Foley from Memorial Sloan Kettering authored the 1986 study. Portenoy had been working under the supervision of Foley, who was respected in the cancer field. Each became a vocal advocate for destigmatizing the use of opioids to treat pain, and Portenoy started speaking at conferences and seminars across the country.
The same year that Portenoy and Foley’s study was published, the World Health Organization published new guidelines for treating cancer pain:
- Begin with non-opioid medications.
- If pain persists, use weak opioids, such as codeine or tramadol.
- If pain persists, use strong opioids, such as morphine or oxycodone.
“The WHO itself was really leery about [publishing] it,” Meldrum said. “They were almost reluctant to publish this, but the cancer pain specialists were insistent.”
The WHO’s 1986 pain relief ladder for cancer pain
While some experts were arguing that opioids might not be as addictive as once thought, others were inventing new medical diagnoses. A 1989 article in Pain found that a 17-year-old patient with leukemia experienced pain that caused symptoms similar to addiction. The study introduced the term pseudoaddiction to describe how inadequate access to pain medication could cause patients to desire pain medications. The authors argued that withholding opioids caused iatrogenic harm, meaning the hospital harmed the patient by withholding treatment. The study recommended establishing trust with the patient and providing appropriate pain medications to relieve the patient’s pain. One of the authors of the article, Dr. J. David Haddox, later took a job at Purdue Pharma, the maker of OxyContin. In a recent article in The New York Times, former Food and Drug Administration Commissioner David Kessler summarized pseudoaddiction as a “flawed concept” that described patients exhibiting drug-seeking behavior as needing help relieving pain instead of addicts looking for drugs. Since the introduction of the theory, more than 200 scientific articles have mentioned pseudoaddiction, and the theoretical phenomenon became a common justification for giving opioids to patients with symptoms of addiction, according to a 2015 review published in Current Addiction Reports. Only 18 studies questioned its plausibility. Of those, 12 supported the concept of pseudoaddiction, including four industry-funded studies. Six studies opposed the theory. None of the studies confirmed the existence of pseudoaddiction using empirical evidence, according to the review.
Lobbying For Pain Relief
By 1990, the pain management movement was gaining momentum. Opioid therapy for the treatment of cancer pain became more common, but some researchers believed opioids could be used for other forms of pain.
They believed that the principles of the WHO’s cancer pain guidelines could be used to treat chronic, nonterminal pain such as arthritis, Meldrum said. In a 1993 interview with The New York Times, Portenoy said, “There is a growing literature showing that these drugs can be used for a long time, with few side effects and that addiction and abuse are not a problem.” In a 1996 interview, Foley talked about how the pharmaceutical industry was helping spread the word about a revolutionary approach to pain management, according to Quinones.
Foley and Portenoy begin to argue that long-term opioid therapy for chronic pain is safe,” Meldrum said. “There actually is no evidence for this.” Opioid advocates, pain societies and pharmaceutical companies began exaggerating the benefits of chronic opioid therapy while minimizing the risks, especially the risk of addiction, according to Kolodny. “The addiction claim, probably more than any other single piece of misinformation, was the most damaging,” Kolodny said. “It was probably the most important claim for drug companies and opioid advocates to lie about because they understood that fear of addiction was the biggest barrier to aggressive prescribing.”
“There is a growing literature showing that these drugs can be used for a long time, with few side effects and that addiction and abuse are not a problem.”
Dr. Russell Portenoy, 1993
The Fifth Vital Sign
The American Pain Society called on physicians to emphasize pain assessment during patient evaluations by calling pain “the fifth vital sign” in 1996. “Vital signs are taken seriously,” APS President Dr. James Campbell said in a 1996 address. “If pain were assessed with the same zeal as other vital signs are, it would have a much better chance of being treated properly.” The Veterans Health Administration jumped on board, adding pain as the fifth vital sign to its national pain management strategy in 2000. The Joint Commission on Accreditation of Health Care Organizations, now called the Joint Commission, followed by adding pain assessment and management standards to its accreditation process. Each of these influential organizations recommended that doctors ask about pain and adequately treat it.
The Influence Of Pain Societies
Portenoy continued to build a reputation across the country. He became the chairman of the Department of Pain Medicine and Palliative Care at Beth Israel Medical Center in New York. He later became the director of the American Pain Foundation, a nonprofit established in 1997 to advocate for pain relief. During the next decade, the American Pain Foundation lobbied against state and federal attempts to limit opioid use. It lobbied to politicians, state medical boards, judges and regulators with stories of people suffering from pain.
Surrounded by members of the The American Pain Foundation, Pain Connection and the Georgia Pain Initiative, Georgia Gov. Sonny Perdue declares September to be Pain Awareness Month (Photo: Flickr via bmpainfoundation)
It claimed it was a grassroots organization, but years later investigations by Pro Publica and The Washington Post revealed that the American Pain Foundation received millions of dollars in funding from pharmaceutical companies. With companies such as Purdue Pharma and Endo Pharmaceuticals funding it, the American Pain Foundation wrote legal briefs in defense of doctors accused of drug trafficking. The organization defended Purdue in a lawsuit involving misleading marketing practices, and it opposed an FDA proposal to force physicians to be certified to prescribe opioids. In its role as an educator for pain relief, the American Pain Foundation produced several pamphlets and guides promoting misleading benefits of opioid treatment and citing questionable research. It was one of a number of organizations backed by drug companies that developed guidelines for opioid use. Meldrum said that pain societies were a result of the growing consensus among many experts that opioid therapy was safe. “There were some organizations and websites that were sponsored by the pharmaceutical companies,” Meldrum said. “But the major organizations, such as the American Pain Society and the International Association for the Study of Pain, were not sponsored by pharmaceutical companies. They did take money from them sometimes.”
Many leaders in pain societies and other experts advocating for opioid therapy believed opioids were safe for patients without a history of substance abuse. After all, most recommendations by pain societies or other organizations recommended opioid use for people with no history of addiction, and they usually told doctors to monitor their patients. “If you monitor the patient, it probably is in many cases worth chronic opioid therapy,” Meldrum said. “The problem is doctors don’t have time to monitor the patient.” Government recommendations followed what was becoming the common consensus in the field. In 1992, the U.S. Department of Health and Human Services held a press conference announcing new guidelines for addressing pain. “We can do more, and we can do better, to control pain after surgery,” HHS Secretary Dr. Louis Sullivan said at the press conference. HHS recommended that doctors prescribe pain medications before patients requested them after surgery.
It denounced myths such as:
- Pain builds character.
- Infants don’t feel pain.
- Elderly patients have higher tolerance for pain.
- Narcotics for postoperative pain are often addictive.
The recommendations came from an extensive review of medical research by expert panels who recommended the new guidelines. “I would say the government was being influenced by the pain management specialists who made a concerted effort to try to get the National Institutes of Health on their side on this issue,” Meldrum said. “NIH and the American Pain Society and the CDC have all over the course of these years published multiple sets of guidelines.” In 1997, a panel from the American Society of Anesthesiologists and a panel comprising experts from the American Academy of Pain Medicine and the American Pain Society announced separate guidelines advocating for expanded use of opioid medications. The guidelines recommended thorough patient evaluations and the use of opioids when other treatments were ineffective. The Federation of State Medical Boards of the United States, which advises medical boards that license physicians, later encouraged policies to address pain management as an integral practice of medicine. The nonprofit organization emphasized that opioids may be necessary for pain relief and that they have legitimate medical purposes. But it cautioned that diversion and abuse were possible. Throughout the 1990s, opioid therapy gained support from experts, government agencies and national nonprofits. The demand for the drugs was created as the suppliers were creating a new product to sell.
Marketing Pain Relief
Pharmaceutical companies have revolutionized the health care industry. They’ve developed medications that improve well-being and save lives. But the industry is not altruistic.
“In some ways, they were actually rather slow to move into the field because the pharmaceutical company’s interest is in selling drugs at profit,” Meldrum said. “In order to do that they have to have a patent. Most of the opioids are not patentable. They’ve been on the market forever.” Before opinions on opioids changed, numerous opiate-based pain relievers were on the market.
Commercial production of morphine begins
Codeine is discovered
Dextromethorphan, the first cough medicine containing codeine, is approved by the FDA
Percocet, which contains oxycodone, is approved by the FDA
Lortab and Lorcet, which contain hydrocodone, are approved by the FDA
Vicodin, which contains hydrocodone, is approved by the FDA
The market was already saturated with competition from brand-name drugs and generic drugs available at a lower price. But the drugs had one thing in common: they provided only short-term pain relief.
Most opiate-based pain relievers in the 1980s worked for up to six hours. They’re called immediate-release drugs because the pills release the full dose of the active ingredient rapidly. That means patients taking immediate-release opioids have to take four doses each day to feel around-the-clock pain relief. Purdue Pharma developed a way to make a morphine pill relieve pain for between eight and 12 hours. But the patent for the drug called MS Contin expired during the late 1980s. The company knew it would lose money because its best-selling drug would have to compete with generic alternatives, according to an investigation by the Los Angeles Times. In 1990, Purdue decided to pursue an extended-release version of oxycodone, a drug that had already been available in immediate-release form for more than a decade. Purdue spent more than $40 million developing the new drug, believing it would be effective for up to 12 hours, according to the L.A. Times. But in one of the first clinical trials involving OxyContin, its effects wore off within eight hours for one-third of the participants. Still, the researchers were able to conclude that the drug relieved pain longer than immediate-release drugs.
The original formula for OxyContin from Purdue Pharma’s 1992 patent application (Image: U.S. Patent ∓ Trademark Office)
Future company-sponsored studies continuously found evidence that the drug was ineffective for 12-hour treatments, and clinical trials allowed patients to use additional pain medications when the drug wore off. In one trial, a Purdue researcher switched his participants to eight-hour doses of OxyContin to provide adequate pain relief, according to the L.A. Times. But the FDA approved the drug for use every 12 hours in 1995 because it was effective in more than 50 percent of patients for that duration. In its review of the drug, the FDA noted that it was not proven to be more effective than immediate-release versions of oxycodone. Purdue also convinced the FDA to label OxyContin as having a lower potential for abuse than other opioids because of its extended-release formula. It was an unprecedented decision.
Promoting The Pill
OxyContin was released to the market in 1996, when the pain relief movement was gaining momentum across the country. According to the L.A. Times, at a 1995 company meeting, a Purdue marketing executive told employees, “We do not want to niche OxyContin just for cancer pain.” The company spent $207 million on marketing to launch the drug. From 1996 to 2001, Purdue held more than 40 pain management conferences in vacation destinations. More than 5,000 health care providers attended the all-expenses-paid events, according to an American Journal of Public Health article. Purdue developed a database that allowed them to determine which doctors were most frequently prescribing opioids. The company systematically targeted those doctors with marketing tactics to increase OxyContin prescriptions. Sales reps achieved financial bonuses for getting doctors to prescribe more drugs in their territories. In 2001, the company paid $40 million in sales incentive bonuses to its employees
The marketing expenses paid for themselves. OxyContin sales grew from $44 million in 1996 to more than $1.5 billion in 2002. In 1996, doctors wrote 316,000 prescriptions for the drug. They wrote more than 7.2 million prescriptions in 2002, according to a Government Accountability Office investigation. The company’s sales pitch included telling physicians that the drug’s 12-hour dosing was more convenient for patients than the four- or six-hour dosages required by competitor’s drugs. It included marketing to doctors for noncancer-related pain. Most of all, Purdue emphasized that opioids were not addictive for chronic pain relief, citing the studies from the 1980s. The company produced patient brochures, videotapes, TV commercials and a website called “Partners Against Pain.” It handed out fishing hats, CDs and toys branded with OxyContin logos. It hired physicians to promote the product at lectures, seminars and conferences.
Purdue Pharma spent $207 million on marketing OxyContin when it was released to the market in 199
“There is no doubt that the upper echelons of the marketing department were probably aware very early on that their formulation was subject to abuse.”
Marcia Meldrum, UCLA
“They were all over the place,” Meldrum said. “They were sponsoring conferences. They had a whole group of what they called educational specialists who went around the country talking to groups of doctors and nurses and explaining how safe and wonderful OxyContin was. And of course people bought this.” Meldrum emphasized that a lot of people, including Purdue’s educational specialists, believed what they were selling was true, but “there is no doubt that the upper echelons of the marketing department were probably aware very early on that their formulation was subject to abuse.”
“He Was Ready To Write Anything”
In 2001, Krystle Pellegrino found her parent’s prescription medications in the bathroom.
At age 15, she started taking Valium and Percocet. Before she knew it, she was taking them regularly and selling them in school. “I didn’t have any idea what I was doing,” Pellegrino told DrugRehab.com. At 16, she went to a long-term rehab for teens. But she ran away so many times that the facility wouldn’t take her back. By age 17, she’d left her parent’s house to live on her own in Long Island. Within a year she was doctor shopping. “Pills were my main problem,” Pellegrino said. “I was doing any pill I could. Back then it was OxyContin and stuff like that.” At first she would get them on the streets or from family members. Then she started getting them from doctors. “Somebody told me to go into the city, and go meet doctors and I might be able to find somebody to give me a script,” Pellegrino said. “That was my new thing. I was script shopping all over. I was able to get a script for Percocet, and I was selling them to get more intense drugs like OxyContin.” She got a prescription for Valium at the first doctor she visited. The next time she saw him, she told him she’d hurt her wrist. It was easy. “He was ready to write anything,” Pellegrino said. “He didn’t even really care. He was just writing me a ton of scripts.”
“He was ready to write anything. He didn’t even really care.”
Ignoring The Evidence
Pharmaceutical companies, like Purdue, that promoted the results of the 1980s studies ignored the results of later studies that examined addiction risk in chronic pain patients.
Marta Nelson of Advanced Recovery Systems discusses causes of the opioid epidemic and the fact that patients who legitimately obtained opioids for pain became addicted to their medications.
Before analysts made the connection between the rise in overdoses and the rise in prescriptions, the warning signs were published in several journals.
A 1992 review of 24 studies published in the Clinical Journal of Pain found that between 3.2 and 18.9 percent of patients with chronic pain developed symptoms of addiction. It concluded that drug abuse diagnoses “occur in a significant percent of chronic pain patients.”
A 1995 study published in the International Journal of Addiction found that 23.4 percent of 414 chronic pain patients at a Swedish hospital had symptoms of alcohol, pain reliever or sedative abuse or dependency. Pain relievers were the most commonly abused drugs.
A 1997 study of 125 chronic pain patients at a London pain clinic found that 12 percent met the criteria for substance abuse or dependence. The study published in the Journal of Psychosomatic Research also found that 17 percent of patients used medications in doses “well above the highest recommended dose.”
A 1997 study published in the Clinical Journal of Pain found that 34 percent of chronic pain patients who received opioids at a VA medical center exhibited one criterion of substance abuse. More than 27 percent met three or more criteria for substance abuse.
During this time, some pain specialists also believed that opioids weren’t effective treatments for chronic pain. And currently no reliable studies have ever been conducted that prove long-term opioid therapy effectively treats pain, according to a 2015 review published in Annals of Internal Medicine. “I’d say the leading pain specialists understood that opioids were bad drugs for chronic pain,” Kolodny said. “Addiction wasn’t so much their concern, they just knew that this is a lousy treatment for chronic pain.” Pain management experts may have disregarded the warning signs for addiction because they believed a new product that had less potential for abuse, OxyContin, was now available. But leaders at Purdue knew better.
OxyContin’s Potential For Abuse
Purdue was allowed to market OxyContin as harder to abuse than its competitors because of its extended release formula. But the company knew that its other extended-release drug, MS Contin, had been abused. A 1990 article published in the journal Cancer documented how MS Contin could be crushed and injected. It presented a case report of a patient who detailed a “commonly used” method for extracting morphine for abuse. The authors verified that the procedure could be used to abuse the drug, and they wrote the study to “alert physicians and allied health professionals of the potential for abuse” of MS Contin. Purdue had determined that OxyContin could be crushed to extract oxycodone in its own tests before applying for FDA approval, according to the American Journal of Public Health article. By 2001, Purdue was facing lawsuits from people who said they had taken the drug at its prescribed dose and become addicted. Other lawsuits alleged the company was responsible for people who were abusing the drug. Five years after the drug entered the market, the state of West Virginia filed a lawsuit against Purdue for violating a state consumer protection law. “They were telling doctors that OxyContin was far less addictive than other painkillers in this class of drugs,” West Virginia assistant attorney general Doug Davis told the Associated Press in 2001. “Now, we have a lot of people addicted to OxyContin in West Virginia.”
“A lot of these people say, ‘Well, I was taking the medicine like my doctor told me to,’ and then they start taking more and more and more. I don’t see where that’s my problem.”
Dr. J. David Haddox, Senior Medical Director for Purdue Pharma
Purdue denied responsibility for the rising addiction rates, despite marketing the drug as less addictive and more difficult to abuse. “A lot of these people say, ‘Well, I was taking the medicine like my doctor told me to,’ and then they start taking more and more and more,” Haddox told the Associated Press in 2001. “I don’t see where that’s my problem.” Haddox had helped coin the term pseudoaddiction in 1989. By 2001, he was the senior medical director at Purdue. Despite the lawsuit and more evidence that OxyContin wasn’t as safe as advertised, the pain management field remained divided. Many doctors saw the lawsuits as a threat to patients suffering from legitimate pain.
Not As Effective As Advertised
Shortly after OxyContin launched, Purdue knew its drug wasn’t as effective as advertised. In 1996, company executives received word that physicians were prescribing OxyContin for more frequent doses because it wasn’t relieving pain for 12 hours. Internal company memos revealed in the L.A. Times investigation showed that company leaders told sales reps to advise doctors that OxyContin had been effective for 12 hours in 100 percent of clinical trial patients, which was far from the truth. By 2000, more than 25 percent of doctors were prescribing OxyContin in eight-hour doses. Sales reps combated the problem by telling doctors to increase the opioid strength they were prescribing, not the frequency. That resulted in higher profits for Purdue.
When a 12-hour dose of OxyContin wears off in just 8 hours, patients often seek additional doses or alternative forms of pain relief, creating an increased risk of addiction.
Prescribing an addictive pill in 12-hours doses causes problems when it wears off after eight hours. All opioids cause dependency when taken for extended periods of time, meaning the brain biologically adapts to the presence of the drug. The brain starts to rely on the drug to function normally. It craves the drug and experiences withdrawal symptoms, including headaches, muscle aches, sweating and insomnia when it doesn’t get it. When OxyContin wore off after eight hours, patients would be in pain until they could take the drug four hours later. Patients who had become dependent would start to experience cravings and go into withdrawal. When their prescriptions ran out or their doctors refused to prescribe it in eight-hour intervals, many patients sought other ways to curb their cravings and ease their pain.
Switching To Heroin
Many people who had become addicted to opioid painkillers switched to heroin when their drugs ran out. Heroin eases cravings and withdrawal symptoms because it affects the brain the same way as prescription opioids. Early in 2000, the U.S. Drug Enforcement Administration had become aware of an increasing number of small-time heroin trafficking organizations across the country. Quinones wrote that the organizations were small enough that they wouldn’t normally warrant the DEA’s attention. But the heroin was much more potent than usual, and it was being sold at a surprisingly low price. At age 19, Pellegrino was driving under the influence of Xanax when she passed out at the wheel. She broke four bones and was rushed to the hospital. She couldn’t walk as a result of her injuries, but she is thankful that she didn’t hurt anyone else. After lying about the cause of the accident, the doctors gave her “a ton of meds.” “They wound up giving me a Dilaudid (hydromorphone) drip,” Pellegrino said. “I loved it. I didn’t even care if I walked again at that point. I was getting it for free. It was legal.”
But the doctors caught on that she was “fishing for pills” when she started physical therapy, so they stopped giving her the drugs. In 2005, at age 20, she switched to heroin for the first time. “Things got crazy,” Pellegrino said. “I was with my first boyfriend, the one who introduced me to heroin, when he overdosed in my arms. It was a traumatic experience for me.” The experience helped her quit using drugs. “I wound up getting clean on my own,” Pellegrino said. “Just cold turkeying it. I didn’t get any support systems or programs. I just did it.”
“I was with my first boyfriend, the one who introduced me to heroin, when he overdosed in my arms. It was a traumatic experience for me.”
Prescribing Out Of Control
Purdue launched an innovative product into the pain relief market at an opportune time for the company. It took advantage of the growing belief among many pain management experts that opioids could be effectively used to treat chronic, nonterminal pain.
“Doctors had been prescribing cautiously because they worried about patients becoming addicted,” Kolodny said. “They were told that addiction was very rare and they were told the fear of addiction was irrational. The term opioidphobia was even used. That was very important for convincing the medical community to prescribe aggressively.”
“The term opioidphobia was even used. That was very important for convincing the medical community to prescribe aggressively.”
Dr. Andrew Kolodny, Co-Founder, Physicians For Responsible Opioid Prescribing
OxyContin, which contains the chemical oxycodone, was the most popular painkiller of the new millennium, but it wasn’t only the one being prescribed.
From 1997 to 2002, prescriptions increased for several drugs:
- Morphine prescriptions increased by 73 percent.
- Hydromorphone increased by 96 percent.
- Fentanyl prescriptions increased by 226 percent.
- Oxycodone prescriptions increased by 402 percent.
Oxycodone is about 1.5 times as strong as morphine. Hydromorphone is five times as strong and fentanyl is between 50 and 100 times as strong. Additional companies followed Purdue’s lead, selling other drugs containing opioids.
Popular products containing opioids sold by pharmaceutical companies in the 1990s and 2000s
Numerous other companies marketed and continued to sell generic opioids and other opiate-based tablets, patches and injections. They made tons of money. From 2005 to 2007, Johnson & Johnson’s Duragesic patch generated more than $4 billion in sales. During the same time frame, Endo’s Percocet family of products made more than $335 million in net sales. Its Opana family made $107 million in its first full year on the market in 2007, and it made about $384 million in net sales in 2011. By 2015, Forbes reported that Purdue’s OxyContin had generated more than $35 billion since 1995.
The Birth Of Pill Mills
Pharmaceutical companies and drug dealers weren’t the only ones profiting from the increased focus on pain relief. Hundreds of doctors realized they could make a lot of money if they quickly, and inadequately, evaluated patients for pain and prescribed opioids. DEA investigations revealed that pain clinics, also called pill mills, began popping up across the country. A 2004 DEA report described how popular the clinics were and how easy it was for one patient to get drugs.
The DEA report found:
- A patient sat in a crowded waiting room for one hour.
- She was examined by staff for six minutes and by a doctor for nine minutes.
- The examination didn’t include checking the patient’s pulse, blood pressure or respiration.
- The patient received prescriptions for three different opioids, a muscle relaxant and an anti-anxiety drug.
More than 1,500 businesses like this South Florida pain clinic opened in a six-year span (Photo: DEA)
In his book, Quinones described how residents in Appalachia would regularly drive to Florida and collect prescriptions. Then they would bring them back to their home state and sell them for double or triple the price. Flights from Huntington, West Virginia to Fort Lauderdale, Florida were nicknamed the OxyContin Express. By 2009, nine of the top 10 OxyContin prescribing counties in the United States were in Florida. In the state, prescription drug overdoses increased by 61 percent each year from 2003 to 2009 totaling 12,642 deaths, according to the Centers for Disease Control and Prevention. During that time frame, 1,501 pain clinics opened in the state. By 2010, 98 of the top 100 oxycodone-prescribing physicians were located in Florida pain clinics. Florida had the most pain clinics, but pill mills were common across the country. Thanks to the relaxed prescribing attitudes among reputable doctors and aggressive marketing from pharmaceutical companies, prescriptions skyrocketed. A 2014 study published in Medical Care revealed that patients did not report more pain from 2000 to 2010. But doctors in outpatient settings diagnosed pain twice as often, and they prescribed opioids for nonmalignant pain at increasingly high rates. Prescriptions for other pain relievers, such as nonsteroidal anti-inflammatory drugs or acetaminophen, did not increase.
Source: Daubresse, M. et al., Medical Care
The prescriptions continued to increase despite numerous warnings in the early 2000s.
Cause For Alarm
The warning signs from the 1990s studies foreshadowed what would become a national epidemic. At the turn of the century, new evidence revealed that opioid use was getting out of control.
By 1999, the U.S. Drug Enforcement Administration was becoming concerned about the reckless prescribing of opioids. It questioned the aggressive marketing tactics of Purdue, leading to a Government Accountability Office investigation.
In 2000, media reports began to reveal widespread opioid abuse and increasing overdoses across the country.
In 2001, the FDA added a black box warning, its strongest warning, to the label of OxyContin. It warned of the drug’s potential for abuse.
Between 2001 and 2002, the DEA arrested 302 individuals and charged $1 million in fines in 257 OxyContin-related cases.
In 2002, the Pharmaceutical Researchers and Manufacturers of America, the trade group for big pharma, and HHS announced voluntary guidelines for marketing prescription drugs. The guidelines advised companies not to pay excessive consulting fees or offer superfluous gifts such as travel and meals.
By 2003, the FDA had issued two warnings to Purdue for using false or misleading advertisements.
In 2003, the GAO completed its investigation and recommended improvements to the FDA and Purdue’s surveillance programs.
During the early 2000s, the DEA was searching for help from the FDA, the GAO and other authorities to get opioid diversion under control. The agency harshly criticized aggressive marketing from pharmaceutical companies.
“The DEA was chasing down doctors who they thought were overprescribing opioids just as they had done for ages, and they were frequently chastised for doing so.”
“The DEA was chasing down doctors who they thought were overprescribing opioids just as they had done for ages,” Meldrum said. “And they were frequently chastised for doing so.” She said that a decade later, the DEA was criticized for not doing enough. The warning signs continued to pour in, but the biggest indicator that opioid abuse was becoming an epidemic came in 2004. That year, the federal Drug Abuse Warning Network, a surveillance system that reported data on drug-related visits to hospital emergency rooms, revealed that increased medical use of opioids was associated with increased abuse of the drugs.
The report did not focus on hydrocodone because it was not approved for the treatment of severe pain. Nonetheless, the authors pointed out that hydrocodone abuse increased 117 percent from 1996 to 2002. In 2005, a study by the American Pain Society published in Pain concluded that prescription drug abuse was prevalent through the country. Unlike illicit drug abuse which was primarily contained to major cities, prescription drug abuse was common in rural and medium-sized cities. By 2008, drug-poisoning deaths surpassed traffic accidents as the leading cause of death from injury in 30 states. Opioids were involved in more than 40 percent of drug deaths that year, and opioid-related deaths had increased more rapidly than any other type of drug-related death since 1999, according to a CDC report.
A New Voice Emerges
There were always experts who opposed using opioids for chronic pain treatment, but their voice wasn’t as loud as opioid advocates who were backed by the money and influence of pharmaceutical companies. “When the money came to the pain organizations from opioid makers, the professional groups and the few people like Russel Portenoy were given the megaphone,” Kolodny said. “Even though leading pain specialists knew that this was a bad idea.” Experts and pain specialists in the American Psychiatric Association, the American Pain Society, the American College of Physicians and other organizations failed to convince their leaders to oppose opioids for chronic pain. “There was no traction,” Kolodny said. “The leadership within these organizations, they were not willing to help us. The only way we could have any traction was to form our own group.” Kolodny and other experts founded Physicians for Responsible Opioid Prescribing, a nonprofit dedicated to reducing opioid-related deaths by promoting responsible prescribing practices.
We formed PROP because within our own organizations we all felt that the prescribing needed to change quickly and we understood that overprescribing of opioids was fueling a public health crisis.”
Dr. Andrew Kolodny, Co-Founder, Physicians For Responsible Opioid Prescribing
“We formed PROP because within our own organizations we all felt that the prescribing needed to change quickly and we understood that overprescribing of opioids was fueling a public health crisis,” Kolodny said. From the beginning, Kolodny and his organization faced opposition from opioid advocates and the majority of the medical community. He said they were viewed as “mean guys who wanted to take everybody’s opioids away.” “When PROP formed, and we first started to speak very critically of long-term opioid use, when we started to say these are, in fact, highly addictive drugs, it was as if it was a taboo,” Kolodny said. “Nobody was saying that. The medical community had accepted the notion that these were not addictive and that fear of addiction was the barrier to treating pain appropriately.”
“I Thought I Would Be Ok”
Pellegrino maintained sobriety for about a year after her boyfriend overdosed. She met a new man. They fell in love and had a child together.
“We had a great life,” Pellegrino said. “We had a house. We had a car. We had a business. Things were great.” In 2009, she had a C-section when she gave birth to her son. The doctor prescribed Percocet for pain relief. She had never told her husband about her history with drugs, and the doctors never asked if she had a history of addiction. “My mother was a nervous wreck, telling me to tell them,” Pellegrino said. “I didn’t tell them. I felt like I was good. I needed them. I had staples in my stomach. I thought I would be OK.” She wasn’t OK. When the prescription ran out, she convinced doctors to refill it twice. She was eventually taking entire bottles of Percocet each day. “My husband started taking the bottles with him to work because he realized they were disappearing,” Pellegrino said. She started hanging out with old friends. Five months after giving birth, she said she was a “full-blown heroin addict again.” Her husband had never tried drugs before, but he was curious about how Percocet would make him feel. He tried one, and he “was all messed up from it.” “One did nothing for me,” Pellegrino said. “I didn’t think he’d get like that. He wound up following my lead, sadly. He never liked pills. He ended up jumping to heroin a lot quicker than I thought.” They both suffered from heroin addiction, and their lives fell apart. “We lost everything,” Pellegrino said. “We lost the house. We lost the business. We lost the car. We eventually lost [custody of] our child.”
“We lost the house. We lost the business. We lost the car. We eventually lost [custody of] our child.”
Taking Pharma To Court
In June of 2001, the state of West Virginia sued Purdue for inappropriately marketing OxyContin. It accused the company of hiding the drug’s addictive potential from doctors and using aggressive marketing tactics, which led to numerous West Virginians to become addicted.
The state of Virginia began investigating Purdue the same year. The state’s attorney general realized that increasing numbers of Appalachian workers who were prescribed OxyContin after being injured on the job were dying from overdoses. West Virginia and Purdue settled the charges of the 2001 case out of court. Purdue agreed to pay a $10 million fine and to support law enforcement efforts and doctor education programs. But the company didn’t admit any wrongdoing in the settlement. Virginia gathered evidence for five years before filing its lawsuit against Purdue in 2006. That case eventually became a federal lawsuit that involved 25 states and the District of Columbia. Kentucky joined the lawsuit in 2007 after 484 people died from OxyContin overdoses in the state the year before. In May 2007, Purdue settled the federal case and three company executives plead guilty to misbranding and fraudulently marketing OxyContin between 1995 and 2001. The company admitted to falsely claiming OxyContin was less addictive, had lower potential for abuse and caused fewer side effects than other pain medications. It paid a $600 million fine, and the three executives agreed to pay $34.5 million in fines.
Three of five charges that Purdue Pharma pled guilty to in a 2007 federal lawsuit (Source: U.S. District Court, Western District of Virginia)
Kentucky, one of the states hit hardest by OxyContin abuse, opted out of the settlement because the state’s attorney general believed the penalty was too weak. The state would have received only $500,000. That case went back to Kentucky state courts. It took eight more years for Purdue to settle Kentucky’s false marketing lawsuit for $24 million. The state received 48 times the amount of money it would have received from the federal settlement.
Evading Penalties, Responsibility
Purdue didn’t promote OxyContin on its own. It partnered with Abbott, a much older and larger pharmaceutical company. The companies contributed nearly equal numbers of sales reps to promoting OxyContin when it was launched, according to a recent STAT investigation. Abbott also rewarded its top sales reps with $20,000 cash and other bonuses. Like Purdue reps, they often made exaggerated or misleading claims. The larger company benefited from increased prescriptions, receiving 25 percent of net OxyContin sales up to $10 million, according to court records obtained by STAT. Between 1996 and 2002, Abbot received around $374 million from OxyContin sales. It stopped promoting the drug, but it continued to receive six percent of net sales from 2003 to 2006. The sales teams for both companies often worked together and compared strategies, and there is evidence that Purdue pressured Abbott to target certain doctors. Abbot avoided negative press and massive legal settlements because Purdue had agreed to protect Abbott from litigation when the partnership began. STAT reported that Abbott was named as a co-defendant alongside Purdue in 306 OxyContin-related lawsuits in 2003, but Abbot told its stockholders that Purdue had to indemnify it in each lawsuit.
Decades of Litigation
Purdue isn’t the only company that was and is still accused of illegally marketing opioids.
In 2006, a Texas court ordered Johnson & Johnson to pay $772,500 to the family of a woman who died when a Duragesic patch leaked. At the time, the FDA was investigating 120 deaths related to pain patches, according to The New York Times.
The FDA issued its second warning involving fentanyl patches to make sure doctors were prescribing the devices to be used exactly as recommended.
In 2008, drugmaker Cephalon plead guilty to a criminal violation of the Federal Food, Drug and Cosmetic Act for its misleading promotion of Actiq and two other drugs between 2001 and 2006. It agreed to pay $425 million in the case brought by the DOJ, 13 states and the District of Columbia. Teva acquired Cephalon in 2011.
In 2010, Alpharma settled false claims allegations brought by the Justice Department for $42.5 million. The DOJ claimed Alpharma misrepresented the safety of Kadian (morphine) and paid prescribers to promote or prescribe the drug between 2000 and 2008.
In recent years, cities, counties and states across the country have filed additional charges against various opioid manufacturers for aggressive and misleading marketing claims. Several of the charges have been dismissed by courts, including one lawsuit brought against six drugmakers by the city of Chicago. The city filed new charges against the manufacturers in 2015. In 2016, Pfizer, the maker of Embeda (morphine and naltrexone), agreed to cooperate with Chicago by adhering to a code of conduct for marketing opioids. Industry insiders believe the company agreed to the terms to avoid being involved in litigation with the city. Earlier that year, Endo settled a $200,000 lawsuit with the state of New York for misrepresenting Opana ER’s risk of abuse and addiction. Suffolk County in New York also filed charges against several drugmakers for false marketing claims in 2016. Other manufacturers have tried to profit from medications designed to help people recover from opioid addiction. More than 30 states have filed lawsuits against the makers of Suboxone, a medication that helps people recover from opioid addiction. The companies are accused of working together to manipulate the market by convincing health care providers to stop using a dissolvable Suboxone tablet when the patent expired. The companies developed a new digestible film and stopped producing the tablet to keep a monopoly on the Suboxone market. The lawsuit accuses drugmaker Reckitt Benckiser of using marketing, price adjustment and other tactics to remove tablets from the market even though the film didn’t have a superior medical benefit compared with the tablet.
Most prosecutors file lawsuits against companies, not people. In general, the companies pay large fines and individuals evade criminal or civil charges. That stance changed in 2015 when Deputy Attorney General Sally Yates issued a memo telling federal prosecutors to pursue charges against individuals. The same year, a Connecticut nurse plead guilty for accepting $83,000 in kickbacks from Insys Therapeutics, the maker of Subsys (fentanyl). It’s common and legal for doctors or nurses to be paid by pharmaceutical companies to speak at conferences, but the money from the companies isn’t supposed to influence prescribing habits. In the case of Heather Alfonso, the pain clinic nurse was one of the top Subsys prescribers to Medicare patients, and she was being paid $1,000 per event to speak at dinner programs. A federal investigation revealed that Alfonso rarely presented information at the dinners, and she often ate dinner with one other person in attendance — an Insys sales rep or a colleague who wasn’t licensed to prescribe. Alfonso admitted to prescribing Subsys for patients with chronic pain, even though the drug is only approved to treat patients with cancer pain. She also said the kickbacks from Insys influenced her prescribing habits. The case was one part of a larger investigation into Insys’s marketing practices. In 2016, the state of Illinois filed charges against the company for marketing Subys to patients without cancer. The same year, the DOJ charged a former Insys salesman, Fernando Serrano, and a former sales manager, Jonathan Roper, with providing illegal kickbacks to doctors to encourage them to sell the company’s drug.
An internal Insys memo from a 2016 lawsuit that illustrates the relationship between doctors and Insys sales reps (Source: U.S. District Court, Southern District of New York)
In December 2016, the DOJ charged six former Insys executives with conspiring to bribe prescribers to illegally prescribe Subsys and conspiring to defraud insurance companies.
These Insys executives include:
- President and CEO Michael L. Babich
- Vice President of Sales Alec Burlakoff
- Vice President of Managed Markets Michael J. Gurry
- National Director of Sales Richard Simon
- Sales Directors Sunrise Lee and Joseph Rowan
Prosecutors said they decided to pursue charges against the company leaders because of the high-risk nature of fentanyl compared to heroin and other opioids.
Evidence against Insys executives detailing directives to sales reps for promoting Subsys to doctors (Source: U.S. District Court, District of Massachusetts)
“Patient safety is paramount and prescriptions for these highly addictive drugs, especially Fentanyl, which is among the most potent and addictive opioids, should be prescribed without the influence of corporate money,” U.S. Attorney Carmen M. Ortiz said in a press release. “I hope [the] charges send a clear message that we will continue to attack the opioid epidemic from all angles, whether it is corporate greed or street-level dealing.” Each of the executives plead not guilty. In October 2017, the founder of Insys, billionaire John Kapoor, was arrested and added to the list of defendants in the case against the six executives. Federal prosecutors allege that as chairman of the board of Insys, Kapoor helped create a scheme to defraud insurance companies and pay kickbacks to prescribers. Insys has been negotiating with prosecutors to settle the case before it goes to trial, according to Reuters.
Targeting Pharmaceutical Distributors
Pharmacies and prescribers don’t get drugs directly from pharmaceutical companies. Middle-man companies called distributors buy from drugmakers and sell to doctors and pharmacies. Distributors McKesson, AmerisourceBergen and Cardinal Health distribute 85 percent of the drugs in the United States. Throughout the opioid epidemic, several distributors failed to adequately report the drugs they were distributing as required by law. But the DEA cracked down on the companies in 2005, according to a recent Washington Post investigation.
“The distributors could have stopped what was going on, but they didn’t. They were doing the bare minimum. Why would you want to cut off a customer that’s paying you $2 million a year?”
Frank Younker, Former DEA Supervisor
The DEA’s initiative required distributors to monitor their drug sales and halt them if they had suspicion that the drugs were being sold illegally. The agency threatened to issue suspension orders if it found that the drugs leaving distributors were causing a public health threat. “The distributors could have stopped what was going on, but they didn’t,” Frank Younker, a former DEA supervisor in Cincinnati, told The Washington Post. “They were doing the bare minimum. Why would you want to cut off a customer that’s paying you $2 million a year?”
After focusing on small distributors, the DEA eventually accused McKesson, the country’s largest distributor, of failing to report hundreds of shipments to online pharmacies. The distributor settled the lawsuit for $13 million in 2008. The same year, Cardinal Health settled a similar lawsuit for $34 million. But Cardinal Health continued to distribute painkillers to suspicious pharmacies run by CVS Pharmacy without reporting it to the DEA. The agency issued a suspension order to stop the shipments, and in 2012 Cardinal agreed to suspend controlled substance distributions from its Lakeland facility for two years because it failed to prevent the diversion of drugs leaving its facility. Three years later, CVS settled a $22 million lawsuit claiming two of its stores illegally dispensed prescription drugs. Another Florida pharmacy was accused of similar charges.
In 2013, Walgreens paid a record $80 million to resolve claims that its distribution facility failed to report suspicious shipments and that its pharmacies knowingly dispensed prescription drugs for illicit use. In January 2017, McKesson settled charges for violating the Controlled Substances Act for the second time in a decade. This time, the company paid a record $150 million fine and was forced to halt sales from four distribution centers. In December 2017, a joint investigation by the Washington Post and 60 Minutes revealed that McKesson may have got off easy. DEA investigators were prevented from seeking charges against executives, and the $150 million fine was a fraction of the $1 billion fine that some DEA investigators wanted to pursue. In October 2017, McKesson shareholder Charlie Steinberg sued 10 McKesson executives and auditors for failing to audit the company’s system to detect suspicious opioid shipments after the company’s 2008 settlement. McKesson lawyers have filed a motion to dismiss all charges. The case is pending in a Delaware court.
An Investigation Without Results
In 2012, the U.S. Senate Finance Committee began investigating drugmakers Purdue, Endo and Johnson & Johnson for their role in societies such as the American Pain Foundation, the American Pain Society, American Academy of Pain Medicine, the Center for Practical Bioethics and the University of Wisconsin’s Pain & Policy Studies Group. The American Pain Foundation closed shortly after the investigation began. Senate investigators “collected and analyzed a mountain of material” during the investigation, and the committee produced a draft of a report, according to a STAT column by former senate investigator Paul Thacker. However, the committee changed leadership in January 2014 and never released an official report. “It is very important that the findings of the Senate Finance Committee’s investigation be made public so that we can understand how opioid makers and nonprofit groups worked together to encourage aggressive opioid prescribing for common conditions like low back pain, where risks of use outweigh the benefits,” Dr. Michael Carome, director of Public Citizen’s Health Research Group, told DrugRehab.com. Public Citizen is a nonprofit based in Washington, D.C., that advocates for a variety of issues including increased physician accountability and safer and more effective drugs. In September 2015, several public health experts wrote a letter to the senate committee’s new leaders, Sens. Ron Wyden, D-Ore., and Orrin Hatch, R-Utah, requesting that they make the results of the investigation public.
“Some of these same companies and nonprofit groups have continued to promote aggressive opioid use and continue to block federal and state interventions that could reduce overprescribing.”
Dr. Michael Carome, Directory Of Public Citizen’s Publish Health Research Group
The letter was signed by Carome and leaders from 35 other organizations including:
- The Johns Hopkins Center for Drug Safety and Effectiveness
- The National Center on Addiction and Substance Abuse
- Physicians for Responsible Opioid Prescribing
- Transforming Youth Recovery
- American Society of Addiction Medicine
- The Hazelden Betty Ford Foundation
“Neither Senator Hatch nor Senator Wyden responded formally in writing,” Carome said. A spokesperson for Wyden has said an official report was never produced and the senators can’t comment outside of an official action or report. “The documents related to the 2012 investigation are currently being reviewed by Democratic investigations staff,” Wyden’s spokesperson Taylor Harvey said. “Senator Wyden intends to take official action related to this investigation.” More than two years have passed since the letter was sent to the senators, and nothing has happened. Senator Hatch’s term is set to expire in January 2019, and he has said that he does not plan to seek reelection. Carome said the results of the investigation are significant “because some of these same companies and nonprofit groups have continued to promote aggressive opioid use and continue to block federal and state interventions that could reduce overprescribing.”
The Epidemic Today
More than 20 years have passed since Purdue began marketing OxyContin. We’ve known that increases in opioid prescriptions are associated with increases in opioid addiction and overdoses for more than a decade. For years, we’ve known that prescription drug addiction leads to heroin addiction in a significant number of people.
But the problem is getting worse.
Dr. Kevin Wandler of Advanced Recovery Systems discusses the opioid crisis and why opioid addiction is difficult to overcome without treatment.
Deaths from drug overdoses continue to increase every year. Overdose deaths grew from a national record of 52,404 in 2015 to 63,632 in 2016. Opioids were involved in 63 percent of drug overdose deaths in 2015, and 66 percent in 2016, according to data from the CDC.
Among heroin users, 75 percent say they used prescription opioids before switching to heroin. From 2014 to 2015, heroin overdose deaths increased by 23 percent across the country, according to the CDC. “One of the reasons the problem got worse for so many years, and one of the reasons we failed to respond appropriately, was that policymakers were hearing from the opioid lobby that all of the bad stuff with opioid deaths were from so-called drug abusers,” Kolodny said. “Up until very recently, policymakers simply accepted that framework,” Kolodny continued.
From 2013 to 2014, heroin overdose deaths increased by 26 percent across the country.
Source: Centers for Disease Control and Prevention
“If you look at what was coming out of the Substance Abuse and Mental Health Services Administration, the Office of National Drug Control Policy and the FDA, the sole focus was on reducing nonmedical use, reducing abuse…. The CDC had been the one exception that, for a while, kept pointing to overprescribing as the problem.” The DEA recently reported that illegal Chinese laboratories were mass producing fentanyl and selling the drug to North American dealers via online pharmacies. Some dealers lace heroin with fentanyl to strengthen their supply and increase profits. Thousands of people who didn’t realize the drug was laced have overdosed. In some parts of the country, carfentanil, an opioid designed to sedate large animals, was added to heroin and lead to massive numbers of overdoses. Fortunately, access to an opioid overdose reversal drug called naloxone has increased. The drug can help someone who has overdosed on heroin regain consciousness in less than a minute. It’s used every day by first responders across the country. Firefighters in Revere, Massachusetts, told Fusion’s Mariana Van Zeller that everyone in the Revere Fire Department has used Narcan (naloxone) at least once.
“We tend to have more overdoses than we do fires, so it’s a piece of equipment that we can’t go without now. Just like we have the hose.”
Kevin Doherty, Firefighter
“We tend to have more overdoses than we do fires,” firefighter Kevin Doherty said. “So it’s a piece of equipment that we can’t go without now. Just like we have the hose.” But naloxone isn’t without controversy. The drug has been available in generic form since 1985, but a 2016 review published in the New England Journal of Medicine found prices of several versions of the drug have increased as the opioid epidemic has worsened.
Generic naloxone price increases:
- Amphastar’s naloxone injection Narcan cost $20.34 in 2009. It cost $39.60 in 2016.
- Hospira’s naloxone injection cost $62.29 in 2012. It cost $142.29 in 2016.
- Kaléo’s auto-injecting naloxone device Evzio cost $690 in 2014. It cost $4,500 in 2016.
Comparatively, Mylan, West-Ward and Adapt’s versions of naloxone have not changed in price in the past two years.
A New Way To Make Money
After admitting that their drugs were subject to abuse, several pharmaceutical companies said they’d fix the problem by making their drugs more difficult to misuse. In August 2010, the FDA approved a reformulated version of OxyContin which had abuse-deterrent properties. The drug is difficult to crush, break or dissolve. After years of post-market analysis, the agency allowed Purdue to add abuse-deterrent language to the drug’s label. Once again, other companies followed Purdue’s lead. They developed drugs that were difficult to crush and melt. They also made pills that released naloxone when crushed, which would block the euphoric effects of the opioid.
ABUSE-DETERRENT DRUGS ON THE MARKET TODAY
- Targiniqoxycodone and naloxone
- Embedamorphine and naltrexone
- Troxycaoxycodone and naltrexone
The drugs may have contributed to increases in heroin use in recent years. Reports indicate that people prescribed abuse-deterrent drugs often turn to heroin or other opioids on the street. None of the drugs are completely safe. With enough effort, they can be crushed or dissolved. People can abuse them by taking doses higher than those prescribed by a doctor.
Developing and patenting the drugs gave pharmaceutical companies an opportunity to continue to make money without competition from generics. “They’re just as addictive as regular formulations,” Judy Rummler, chair of the FED UP! Coalition, told Drug Rehab.com. The coalition advocates for federal action to end opioid addiction and overdose deaths. “Because there are new patents, the pharmaceutical industry has found a way to make a lot of money on these things,” Rummler said. “That’s something that people need to be made aware of. There is no proof that these are effective at ending the opioid epidemic, and they’re just as addictive as the regular formulations.” An Associated Press and Center for Public Integrity investigation revealed that companies made a combined $2.4 billion on abuse-deterrent drugs in 2015. Purdue’s abuse-deterrent OxyContin formula is the most popular, and patents protect it until 2030. The pharmaceutical industry has spent hundreds of thousands of dollars lobbying for legislation that requires insurers to cover the abuse-deterrent drugs. Since 2012, 21 bills pushed by industry lobbyists have become state law, according to the Associated Press report.
“There is no proof that these are effective at ending the opioid epidemic, and they’re just as addictive as the regular formulations.”
Judy Rummler, Chair, Fed Up! Coalition
Admitting Their Mistakes
The pain advocates of the 1990s and early 2000s have since backed away from their exaggerated claims. Many of them had always said that chronic pain patients should be evaluated for past substance abuse issues and be closely monitored. But they often relied on scant evidence to prove their claims. “A number of people in the leadership have basically sort of retreated,” Meldrum said. “A number of government agencies are sort of retreating as well.” In 2011, Kolodny and PROP uploaded an interview featuring Portenoy to YouTube in which the longtime opioid advocate showed regret for previous statements. “I gave so many lectures to primary care audiences in which the Porter and Jick article was just one piece of data that I would then cite,” Portenoy said in the video. “I would cite six, seven, maybe 10 different avenues of thought or avenues of evidence, none of which represented real evidence. “What I was trying to do was to create a narrative so that the primary care audiences would look at this information [in all] and feel more comfortable about opioids in a way they hadn’t before. In essence, this was education to destigmatize, and because the primary goal was to destigmatize, we often left evidence behind.” “Clearly, if I had an inkling of what I know now then, I wouldn’t have spoken in the way that I spoke. It was clearly the wrong thing to do.”
In a 2012 interview with The Wall Street Journal, Portenoy said he may have focused on the benefits of opioids without emphasizing the risks. “Did I teach about pain management, specifically about opioid therapy, in a way that reflects misinformation?” Portenoy said. “Well, against the standards of 2012, I guess I did. We didn’t know then what we know now.” Other organizations also owned up to their role in the epidemic. In an email to CNN, the Joint Commission’s executive vice president for health care quality said the organization had relied on faulty research. “There is no doubt that the widely held belief that short-term use of opioids had low risk of addiction was an important contributor to inappropriate prescribing patterns for opioids and the subsequent opioid epidemic,” Dr. David W. Baker said. “The Joint Commission was one of the dozens of individual authors and organizations that developed educational materials for pain management that propagated this erroneous information.” In 2016, the American Medical Association approved a resolution to remove pain as a fifth vital sign from professional standards, joining the Physicians for Responsible Opioid Prescribing in lobbying the Joint Commission to soften its pain management standards. The VA has also removed language involving pain as a vital sign from its standards.
“I would cite six, seven, maybe 10 different avenues of thought or avenues of evidence, none of which represented real evidence.”
Dr. Russell Portenoy
A 12-Month Wait For Treatment
After she relapsed, Pellegrino and her husband lived on the streets of Long Island for years. She thought about going to a methadone clinic for help. One of her friends had gone to a clinic and been able to recover. But the waiting lists for the methadone clinics on Long Island were 12 months long.
Pellegrino and her husband eventually moved to the streets of Manhattan, begging for food and money for drugs. Everyone on the street was using drugs. When they couldn’t find them, they would go to the methadone clinic to avoid withdrawal, she said. In the city, the waiting lists were shorter. In the summer of 2015, Pellegrino decided to go for the first time to avoid getting sick when she couldn’t afford heroin. “Ever since then, I’ve never used an [illicit] opioid,” Pellegrino said in December 2016. “I’m still on the methadone, but I’m tapering off and by the New Year, I’ll be off methadone. Once I was free, I wasn’t getting sick and I was able to get into a shelter, I knew I didn’t want to go back.” Her husband is in recovery, too. Neither has relapsed during the last 18 months of methadone treatment. “The progress is slow,” Pellegrino said. “We live in a New York City shelter together. We go to the methadone clinic. We both have jobs. We’re struggling to get an apartment.” She said she battles immense feelings of guilt for losing custody of her son, who currently lives with her in-laws on Long Island. “Once we get an apartment, we’ll be able to go to court and fight for child custody,” Pellegrino said. “That’s my goal.”
“Once I was free, I wasn’t getting sick and I was able to get into a shelter, I knew I didn’t want to go back [to heroin].”
The Smallest Victims Of Opioids
As opioid abuse and addiction increased in the United States, the number of babies born addicted to the drugs also grew. In 2003, 5,000 babies were born dependent on opioids because their mothers used the drugs during pregnancy. That year, Congress passed the Keeping Children and Families Safe Act, a law that funds a variety of child protective service programs. But the number of babies born with neonatal abstinence syndrome, a syndrome in which newborns experience withdrawal, increased each year from 2003 to 2013. More than 27,000 drug-dependent babies were born in 2013, according to a Reuters report.
Some moms, like Pellegrino, relapse after giving birth. Her son and thousands of other children are now being raised by their grandparents. The number of children in the custody of their grandparents increased by 4,000 from 2005 to 2015, according to a report by Stateline, an initiative of The Pew Charitable Trusts. When these children don’t have grandparents, the state becomes responsible for their care. That’s overwhelmed states such as Ohio. The Public Services Association of Ohio reported that opioid addiction led to a 19 percent increase in the number of children taken into protective custody between 2008 and 2015, according to the Associated Press. A 2016 report to the Senate Committee on Homeland Security and Governmental Affairs outlined increases in the number of children receiving out-of-home-care.
Children Receiving Out-Of-Home Care:
- 2013: 397,153
- 2014: 400,989
- 2015: 415,129
Source: Senate Committee on Homeland Security and Governmental Affairs
Those numbers are composed of children entering out-of-home care and children remaining in care. In 2014, about 265,000 children entered care. The majority of them were infants.
Searching For Solutions
During his final year in office, President Barack Obama made fighting the opioid epidemic a top priority for his administration. He requested $1.1 billion from Congress to fight addiction, and Congress passed the Comprehensive Addiction and Recovery Act of 2016 in July. The law authorized $181 million in new funding for prevention, treatment and recovery efforts.
In December 2016, Congress passed the 21st Century Cures Act which included $1 billion to fight opioid addiction in 2017 and 2018. Obama signed it into law less than a week after it was passed. Earlier in 2016, the president appointed Agricultural Secretary Tom Vilsack to fight heroin and prescription drug abuse in rural America. The goal of Vilsack’s Rural Impact initiative was to bring jobs and educational programs to rural America to boost protective factors in those communities. Obama spoke with Grammy Award-winning artist Macklemore about the opioid epidemic in a 2016 MTV documentary. The goal of the documentary was to help raise awareness about opioid addiction and to inspire people to seek help.
President Barack Obama and Macklemore discuss the opioid epidemic in America (Source: whitehouse.gov)
Macklemore and singer Ariana Deboo recently released a song titled “Drug Dealer” describing how Purdue Pharma and doctors who received financial kickbacks from the industry contributed to the epidemic. Other celebrities in recovery have also helped build support for addiction-related issues. Actress Jamie Lee Curtis spoke about her recovery from alcohol and Vicodin addiction at a fundraiser for the Council on Drugs and Alcohol in Houston. Actor Matthew Perry, who is also in recovery from alcohol and opioid addiction, spoke to Congress about securing funds for treatment programs in the criminal justice system. He advocates for the National Association of Drug Court Professionals. Across the country, families of people affected by opioid addiction have started nonprofits, community coalitions and advocacy groups to prevent substance abuse, destigmatize addiction and provide resources for those who need them. “You’ve seen governors around the country saying that overprescribing is the problem,” Kolodny said in 2016. “President Obama began weighing in on the problem this year, and he talked about overprescribing. The CDC continued that message and the surgeon general has certainly carried that torch. “We’re beginning to understand this problem, not as a problem of drug abuse, or nonmedical use or even heroin abuse. Policymakers are recognizing that we have an epidemic of opioid addiction fueled by overprescribing of opioids.”
2016 Opioid Prescribing Guidelines
In March 2016, the CDC released new guidelines urging doctors to use opioids only when no alternative medications were possible. It advised prescribers to thoroughly evaluate patients, check prescription drug monitoring programs, prescribe the lowest dose possible and monitor patients frequently.
“We know of no other medication routinely used for a nonfatal condition that kills patients so frequently.”
CDC Director Tom Frieden
Writing in the New England Journal of Medicine, CDC Director Tom Frieden said, “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently.” Two weeks after the guidelines were released, the White House announced that 61 medical schools agreed to require students to receive prescriber education in line with the CDC’s guidelines. The American Dental Association has urged dentists to increase efforts to prevent opioid addiction. The American Medical Association has developed resources for physicians to learn about opioid abuse, the stigma associated with substance use disorders and how to use prescription drug monitoring programs. Every state except Missouri has enacted legislation to fund prescription drug monitoring programs which are designed to reduce doctor shopping and identify patients at risk for substance use disorders. These and other attempts at reducing unnecessary opioid prescriptions seem to have started making an impact. A 2017 CDC analysis found that total prescriptions for opioids peaked in 2010 and declined each year through 2015. It was the first decline since 1996, the year OxyContin was introduced.
Still Work To Be Done
Pellegrino lives in a shelter where she hears about people getting prescription opioids from doctors all the time. She said she’s known people who would get teeth pulled just to get Vicodin. It’s still easy to doctor shop, she said. “Most people in the shelters are still using,” Pellegrino said. “I’m around it constantly. I see needles in the bathrooms. I hear them talk about it.”
She had to have mouth surgery recently, and she was petrified that she’d be prescribed opioids. “I had a lot of anxiety about them putting me under and medications,” Pellegrino said. “I was honest for the first time, and I told the dentist about my history. He really worked with me. I wound up just going home with ibuprofen, and honestly that works better than the pain pills anyway.” She’s glad she told him, and she said many doctors are becoming more aware of opioid addiction. “I think they’re a little more used to the story when you tell them, but they’re hopeless to pick up on the signs,” Pellegrino said. “They’re still quick to still prescribe them, even knowing the consequences and what’s happened to so many people.”
“They’re still quick to still prescribe them, even knowing the consequences and what’s happened to so many people.”
President Trump Declares Opioid Emergency
Then presidential candidate Donald Trump promised to help people addicted to opioids find treatment during the 2016 presidential campaign. In August 2017, President Trump told reporters that he was going to declare the opioid epidemic a national health emergency based on recommendations from his commission on combating drug addiction. In October 2017, Trump signed an executive order officially declaring the opioid epidemic a national emergency. “I am directing all executive agencies to use every appropriate emergency authority to fight the opioid crisis,” Trump said at the White House. “This marks a critical step in confronting the extraordinary challenge that we face.” The president promised to launch an opioid awareness campaign, to crack down on fentanyl trafficking, to expand access to naloxone and to launch a task force to create best practices for pain management. He also announced a partnership between the National Institutes of Health and the pharmaceutical industry to search for ways to develop safe pain management medications.
Still Searching For Relief
The pain management field is still trying to find a way to effectively relieve pain without putting patients at risk for addiction. The country is still trying to find a way to reduce the number of people addicted to pain relievers without increasing the number of people seeking heroin. In 2016, more than 2.1 million people were addicted to opioids, including 626,000 who were addicted to heroin, according to the National Survey on Drug Use and Health published in September 2017. About 718,000 people received treatment for prescription opioid addiction that year. But treatment doesn’t always lead to recovery. Between 40 and 60 percent of people relapse after receiving addiction treatment. Pellegrino said recovery isn’t easy, especially in her current living conditions. But she knows what she has to do to avoid relapse. She knows she can’t go back to Long Island because there are too many triggers there. “Everybody says it: persons, places and things,” Pellegrino said. “You have to remove yourself from where you are to clear your mind and get past it.” Peer support is one of the best resources for people trying to overcome addiction. That’s why Pellegrino created a private group called “Recovery Warriors Family” on Facebook to help people affected by addiction. After two weeks, 172 people had joined. “It’s a closed support group,” Pellegrino said. “Its people sharing stories, and if someone posts that they’re struggling, I’ll message them to try and help them. I feel like if I had that, maybe it would’ve been different.”
Her group is one of several groups on social media networks where people from across the country connect to share their stories. They talk about the struggles of addiction and how to find help. They talk about how much their lives have improved since they’ve been in recovery. “My life has changed,” Pellegrino said. “If you get clean, everything can really get put back together. But it’s not going to be overnight.” The lives of people living in chronic pain have changed, too. Reports have surfaced indicating that people with legitimate, severe pain have had trouble finding effective pain relief. They say doctors are now too scared to prescribe the drugs. “The problem is: if you are not using opioids, what do you use instead?” Meldrum said. She said other combinations of cognitive behavioral therapy and physical therapy may be effective, but they are rarely covered by insurance. They also require more time and effort than swallowing a pill. Today, the search continues. Pain experts are still seeking a safe, effective and accessible way to relieve chronic pain. Millions of people who have become addicted are looking for ways to recover. But more resources for heroin addiction are available today than ever before, and relief from addiction is possible for those who seek treatment.
“If you get clean, everything can really get put back together. But it’s not going to be overnight.”
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