Driving home from a hunting trip in 2008, Johnny Sullivan called his wife to say he was having trouble staying awake.
It was early afternoon, but Mary Lou Sullivan wasn't surprised. Her husband was a long-time user of the narcotic painkiller OxyContin (oxycodone) and frequently dozed off as a side effect,sometimes in the middle of chewing his food.
About 10 years earlier, Sullivan and six other chronic pain sufferers had been featured in a Purdue Pharma promotional video for the drug, which Purdue makes. In the video, Sullivan stood at a construction site and talked about how the powerful narcotic eased his back pain and enabled him to run his company again.
But a few years after being prescribed OxyContin, Sullivan became addicted to it and other prescription opioids, his family said. That afternoon in 2008, Sullivan, 52, fell asleep while driving and flipped his truck on a country road in North Carolina.
"I told my sons one day 'that medicine is going to kill him,'" his widow said.
Expanding the market
Purdue Pharma's marketing of OxyContin in the late 1990s marked the beginning of the industry's push to promote narcotic painkillers for treatment of chronic pain -- an indication for which both safety and efficacy remain unproven.
The first decade of the 21st century has been a good one for makers of prescription painkillers as sales quadrupled from 1999 through 2010, but even in a growth industry OxyContin stands out -- ringing up sales of nearly $3 billion a year.
Meanwhile, health officials and regulators have declared a national epidemic as addictions to prescription painkillers have skyrocketed and fatal overdoses have more than tripled in the past decade.
A U.S. Senate investigation -- prompted in part by Journal Sentinel/番茄社区 reports -- is probing financial relationships of drug companies and the doctors and organizations that have advocated for use of the drugs.
Against that background, emerges as a case study of marketing running ahead of science in the pursuit of the bottom line.
The video, made 14 years ago, showcased ordinary people who spoke glowingly of their experiences with OxyContin.
· Two of the seven patients died as active opioid abusers.
· A third became addicted, suffered greatly, and quit after realizing she was headed for an overdose.
· Three patients still say the drug helped them cope with their pain and improved their quality of life.
· A seventh patient declined to answer questions.
The doctor who not only played a starring role but also recruited his patients for the video now concedes some of his statements caught by the camera went too far.
In the video, the doctor, Alan Spanos, MD, a paid specialist in North Carolina, urged doctors to consider prescribing opioids more often.
Spanos, who was once a paid promotional speaker for Purdue, now says the video was meant to be one teaching aid used in lectures by experienced doctors.
But it was unclear then, and remains unclear now, what percentage of patients benefit from the drugs.
"We don't know whether success stories like this are one in five, one in 15, one in 100, one in a thousand", Spanos said in an interview. "They may be quite rare."
Nonetheless, the video was distributed to 15,000 doctors as part of a marketing campaign in which Purdue claimed, among other things, that the drug was less addictive and less subject to abuse than other drugs.
That wasn't true, and in 2007 The Purdue Frederick Co., an affiliate of Purdue Pharma, agreed to pay $634.5 million in penalties for misbranding the drug as part of a U.S. Justice Department investigation.
The sanctions didn't stop the pharmaceutical industry from promoting OxyContin and other narcotics for people with chronic, long-term pain -- a much larger group of potential customers than just those being treated with opioids for intense short-term pain caused by cancer and end of life pain or acute pain caused by severe injuries or surgery.
Building the market
At the time the video was produced, clinicians were often reluctant to prescribe narcotic drugs for chronic pain, fearing the risk of addiction and having little evidence of the drugs' long-term safety and effectiveness.
That changed as Purdue Pharma and other drug makers rolled out broad campaigns aimed at convincing prescribers of the efficacy and safety of their products. At the same time, professional organizations and associations that write treatment guidelines began endorsing opioids for chronic pain. Many of the people writing those guidelines had financial ties to the drug companies.
Over time, doctors began writing more and more prescriptions for opioids -- including Oxycontin, Vicodin (hydrocodone bitartrate and acetaminophen) and Percocet (acetaminophen and oxycodone) -- for more and more chronic conditions, such as back pain, fibromyalgia and arthritis.
Part of OxyContin's unique appeal was that it was a time-released version of the generic painkiller, oxycodone. Patients only had to take two pills a day, which allowed them to sleep through the night without having to get up to take more medicine.
In the 1998 video, Spanos says opioids "don't wear out," meaning patients won't need stronger doses over time.
However experts say it's common for opioid medications to lose their painkilling effect as patients develop tolerance, leading doctors to increase doses.
"Humans develop tolerance to opioids and -- pharmacologically and physiologically -- this is a well-known fact that was also well-known in the 1990s," said Beth Darnall, PhD, president of the Pain Society of Oregon and an associate professor at Oregon Health & Science University.
It worked well at first
Consider Lauren Cambra, one of the seven patients in the video. She was in her mid-40s and suffering from severe low-back pain until she went to see Spanos, who prescribed OxyContin.
"I was pain free," she said in an interview with the Journal Sentinel/番茄社区. "I was able to get up. I could walk up a flight of stairs. I was very happy with the therapy."
Then her dose had to be doubled. Eventually it was doubled again.
She lost her job in the Dot-Com collapse and could no longer afford the $600 a month she needed for OxyContin. When she tried to do without, she spent days on the couch curled up with withdrawal symptoms.
"The next month, I knew I was going to figure out how to get the money," she said.
Instead of paying her bills or her mortgage, Cambra bought OxyContin. She lost her car and her home. She filed for bankruptcy.
Eventually, over a period of months, she weaned herself off the drug.
"I thought that if I didn't stop doing this, if I didn't get off this medicine, I'd probably end up dead," she said.
Today she is managing her back pain the way she did before she went on OxyContin. If she has a flare up, she gets a prescription for a few days of a different opioid, such as hydrocodone (Vicodin). Then she stays off the drugs completely for weeks or months.
"You could not get me to take another OxyContin," she said.
Estimating the tolerance risk
Looking back on his claim that opioids didn't wear out, Spanos said he wanted to address a 1990s stereotype that all patients would develop tolerance and need higher doses.
"I would hope that what was conveyed in the video is that there are patients in whom tolerance doesn't happen," Spanos said.
In an email, Purdue spokesman James Heins said that OxyContin labels have always included warnings about side effects and tolerance, and they're updated when new medical evidence emerges.
He noted the video was made 14 years ago and has not been shown in a decade. He also said he could not comment on what happened to the patients in the video without obtaining their permission.
Heins said statements made in the video reflected the medical consensus regarding opioids at the time.
In fact, Spanos claimed in the video that the rate of addiction among pain patients was much less than 1%.
Spanos acknowledged in a July interview that the 1% addiction figure did not come from long-term studies of chronic pain patients and that he went too far by suggesting it did. He said he regretted it if doctors got the wrong message. It has since has become clear that the percentage of patients who are addicts or will become addicted is "all over the place," Spanos said.
"Those of us who were impressed by the clear benefits for patients did not have a big enough eye on the possible unintended consequences of our enthusiasm rubbing off onto some of our colleagues,," Spanos said of opioid painkillers. "They should be reserved for people for whom the benefits justify the risks and baggage that come with the drug and the most tricky problem is that we do not know the size of the risks."
Today, the National Institute on Drug Abuse says studies among chronic pain patients have found addiction rates from 3% to 40%.
Purdue Pharma spokesman Heins said the rate of addictive disorders among chronic pain patients has not been established by prospective studies. He said the current literature suggests it ranges from less than 1% to 24%.
At least part of the discrepancy in addiction estimates has occurred because many studies exclude patients with prior substance abuse problems. However, real-world pain treatment does not.
When OxyContin was approved in 1996 there was less concern about addiction because opioids were being used mainly to treat cancer and short-term pain, said Mark Sullivan, MD, professor of psychiatry and behavioral sciences at the University of Washington in Seattle.
"They just didn't have the relevant addiction data," Sullivan said.
Addiction and pain
At least three of the seven patients in the video, including Johnny Sullivan, struggled with addiction.
Ira Pitchal, who had fibromyalgia, said in the video that OxyContin allowed him to exercise and do physical therapy, which reduced his cholesterol and returned his blood pressure to a healthy level.
A few years later, Pitchal was found dead in his Florida apartment at age 62.
The cause of death was listed as high blood pressure and cardiovascular disease, though lab tests showed the presence of two opioids in his system, nalbuphine and oxycodone.
Numerous medications were found in his kitchen cabinet and he had pills in his pocket, according to a sheriff's department report.
Pitchal had a history of alcohol and narcotic painkiller abuse, the report said. He had been released from a detox center a month before his death.
A cousin, Marilyn Frey, said Pitchal had suffered from mental health problems for years and may have doctor-shopped for pills.
"He was on gobs of medicines, probably a whole bunch at the same time that he should not have been on," she said. "So many folks who use lots of drugs perhaps would be better off with ibuprofen and some really good (psychological) therapy. I think he was one of them."
Limited research suggests that about 30% of pain clinic patients may benefit from using opioids for long-term pain, according to Ed Covington, MD, director of the Neurological Center for Pain at the Cleveland Clinic. For those best-case patients, the average pain level is reduced by an estimated 30%, he said.
Rigorous clinical trials still have not been done to measure the long-term safety and effectiveness of opioids for various kinds of chronic pain. Without such research, it is difficult to know who is likely to benefit and who is likely to be harmed.
"My biggest complaint is that they (opioids) were pushed by all the zealots in a misleading way," Covington said. "So we were given a false choice - agony without opioids, comfort with."
But when it works...
Three patients in the video say they have greatly benefited from taking OxyContin to manage their long-term pain. Two of the women had severe, debilitating conditions while the third has taken the powerful painkiller for nearly 15 years to deal with back pain.
Mary Dell, who asked that her last name not be used, said in the video that she felt normal for the first time in a decade after taking OxyContin. She had undergone spinal surgery and suffered from back pain for years.
Mary Dell, now 73 and a biotechnology researcher in North Carolina, said not much has changed for her since the video was filmed. She still takes OxyContin every day.
"I would not be able to do the work I love here if I did not take the medicine," she said. "I would be lying on the bed with a heating pad."
OxyContin also made life livable for Dorothy, a patient who asked that she be identified only by her first name.
Dorothy appeared in the video wearing a neck brace. She had been in a car accident five years earlier and had spent the time since trying to control her neck and back pain. At times, she was in so much pain she felt like a "badly injured animal" with no appetite. She remembered staring at a salad one day, unable to move to put the food in her mouth. Riding in a car was unbearable, she said.
Dorothy said Spanos monitored her medication closely and made it clear she shouldn't get narcotics from other doctors in addition to him. The drugs helped her recover from her injury. She was able to move around more and strengthen her muscles. She could keep appointments with friends and not just live hour-to-hour in her house, she said.
"As the pain got better, I got out more," she said. "Life became more predictable."
The drugs were strong, Dorothy said, and the thought of withdrawal frightened her. Her mouth was often very dry, a common side effect of opioids.
But she never felt out of control and the side effects were worth it, she said.
Dorothy said she stopped taking OxyContin in 2004 or 2005 because she got to a point where she was able to function without it.
OxyContin was "a lifesaver" for Susan, another patient in the video who asked that her last name not be used because she is still taking the medication.
Diagnosed with rheumatoid arthritis at age 25, Susan had undergone more than a dozen surgeries, including several on her hip as well as knee replacements, wrist surgery, ankle surgery, fusing of her neck and a hysterectomy.
Susan had tried for years to manage her pain. Some doctors thought she was an addict seeking pain pills, she said. The pain was so bad that she discussed suicide with her husband. Before finding Spanos and OxyContin, she was required to pick up one day's worth of medicine at a pharmacy each morning.
In the video, Susan said finding the right medicine made her life "wonderful again."
"I have found life again and it is worth living now. And I'm so grateful," she said.
Fourteen years later, Susan is still taking OxyContin. She had been taking a massive dose when the video was filmed. Now her dose is about one-tenth of that and she still deals with major pain. She can barely turn her head because her neck is fused, and her wrists are permanently crooked. Her husband Kevin has to help her stand up and she walks slowly, often grimacing in pain.
"If Susan didn't have the painkillers, she couldn't function at all," Kevin said.
For a few years after the video, Susan worked as a paid speaker for Purdue, giving talks at medical schools and to doctors.
The three patients in the video who say OxyContin has helped them are worried that additional restrictions on prescribing narcotics might prevent people like them from getting the pain relief they need.
In July, a group of nearly 40 doctors, researchers and public health officials petitioned the FDA to change the labeling on opioids in ways that would make it more difficult for drug companies to market the medications for chronic, non-cancer pain lasting longer than 90 days.
The recommended changes, if approved, might prompt Medicaid, Medicare and many private insurers to impose restrictions on paying for opioids -- hurdles that would hurt patients who benefit from the potent painkillers, according to doctors who advocate use of the drugs for long-term care.
A better approach would be to improve doctor education, especially in the area of monitoring patients for early signs of addiction, said Lynn Webster, MD, president-elect of the American Academy of Pain Medicine, in a statement.
What about side-effects?
In the video, Spanos downplayed the risk of sedation and doctors' concerns that patients on narcotics seem "sleepy and vague" and "look stoned all the time."
"Nothing could be further from the truth," he said, noting that sedation usually settles to "little or nothing within two weeks."
Numerous papers in medical journals -- published both before and after the video -- warn of the sedative effect of opioids like OxyContin.
Doctors say drowsiness can lessen in two weeks in some patients, but remain an ongoing problem for others, especially when on high doses.
Such sedation can lead to respiratory depression and even fatal overdoses.
"Enough opioids can make you sleepy to the point of dead," said Deborah Grady, MD, a professor of medicine at the University of California, San Francisco and a physician at the San Francisco VA Medical Center.
Spanos said in an interview he agrees high doses can cause sedation but those who are sedated long-term are being "over-treated."
Spanos said it remains unknown how many patients will have a "stellar response" from taking opioids.
"Back then, we all just assumed that someone, somewhere was doing rigorous studies ... and so we'd know the numbers pretty soon," he said.
"And we still don't."
The last ride
Opioids didn't just make Johnny Sullivan sleepy. They overpowered him, said his widow Mary Lou.
"He would fall asleep while we were eating," she said. "I'd hear him gasping for breath."
Early on, the drug seemed to help Sullivan, his wife said.
But then his doses had to be increased.
Sullivan had been prescribed both OxyContin and morphine. He alternated between the drugs and made sure they were never out of reach.
He kept a pouch filled with pills hidden under the seat of his pickup truck. Mary Lou said she did not know which drug he was taking at the time of the accident and a blood test was never done.
At least twice he was taken to the hospital because of an accidental overdose, Mary Lou said.
One trip to the hospital began with a strange incident at a restaurant.
"He had a hamburger, but instead of biting the hamburger he would actually be biting his hand," she said.
Mary Lou took him the emergency room and he was put in intensive care for 24 hours, but he never remembered the incident.
As time went on, the drug had more profound affects, Mary Lou said.
She had to put on his socks and shoes, shave him and wash his hair.
Sullivan's family said they were hesitant to confront him about his addiction because they knew he was in pain.
He didn't acknowledge having problems either, and still painted a positive picture in a second video that Purdue distributed in 1999.
"Never a drowsy moment around here," Johnny Sullivan said, his voice slurred and his eyes heavy.
This story was reported as a joint project of the Journal Sentinel and 番茄社区.