PORTSMOUTH, Ohio — The label on OxyContin, which was approved by the FDA, initially said the risks of addiction were “reported to be small.”
The New England Journal of Medicine, the nation’s premier medical publication, informed readers that studies indicated that such painkillers posed “a minimal risk of addiction.”
Another important journal study, which the manufacturer of OxyContin reprinted 10,000 times, indicated that in a trial of arthritis patients, only a handful showed withdrawal symptoms.
Those reassuring claims, which became part of a scientific consensus, have been dropped or called into question in recent years, as many in the medical profession rediscovered the destructive power of opiates. But the damage arising from those misconceptions might have been vast.
The nation has been overwhelmed by an ongoing epidemic of addiction to prescription painkillers — more widespread than cocaine or heroin — that has left nearly 2 million in its clutches, according to federal statistics.
“It turns out that the doctors didn’t know what they were talking about,” said Barbara Howard, whose daughter, a home-care nurse, died of an overdose in 2009 in southeast Ohio, an area devastated by the epidemic. She had developed a habit after knee surgery.
A closer look at the opioid painkiller binge — retail prescriptions have roughly tripled in the past 20 years — shows that the rising sales and addictions were catalyzed by a massive effort by pharmaceutical companies to shape medical opinion and practice.
Opioids are a class of powerful drugs, often used for pain, that includes morphine, heroin and brand names such as OxyContin, Vicodin and Percocet.
For years, doctors had been cautious about prescribing opioids to anyone except patients with cancer or in acute pain.
But drug manufacturers and some pain specialists helped create a body of scientific research assuaging the long-standing worries about opioids and pushed to expand the use of the drugs in people with chronic pain: bad backs, arthritis, sore knees.
Their studies reported minimal risks of addiction and dependence. These, in turn, were accepted by the FDA and the nation’s medical journals. State medical boards made their rules for prescribing opioids more liberal. Academic and industry articles dismissed the old fears as “opiophobia.”
These reports reached doctors through marketing efforts and told them that there were few risks in using opioids to treat chronic pain.
According to a Washington Post examination of key scientific papers, a court document and FDA records, many of those claims were developed in studies supported by Purdue Pharma, the maker of OxyContin, or other drug manufacturers. In addition, the conclusions they reached were sometimes unsupported by the data, and when the FDA was struggling to come up with an opioid policy, it turned to a panel populated by doctors who had financial relationships with Purdue and other drugmakers.
A review of 16 key clinical trials on the subject shows that five were funded by Purdue and an OxyContin distributor, two were co-authored by Purdue employees, and two were sponsored by other drug companies making different opioids. None of the 16 studies showed clear warnings about the addiction dangers or the physical dependence generated by the drugs. And the low rate of addiction reported in these studies is at odds with more recent findings.
Internal company documents indicate that one of the key published studies sponsored by Purdue — the one reprinted 10,000 times — omitted suspected cases of withdrawal symptoms. The published paper offered assurance that only two of more than 100 OxyContin patients had withdrawal symptoms; the internal documents showed that at least 11 exhibited possible signs of withdrawal, and some experts say it is likely that at the doses given most of the patients would have experienced withdrawal.
To refine its policy on opioids, the FDA convened a key meeting in 2002 and invited 10 outside experts for advice. Five of them reported having served as speakers or investigators for Purdue. Three others reported working as speakers for or as advisers and consultants to other pharmaceutical companies.
One of those FDA advisers, Russell Portenoy, who was then the chair of the Department of Pain Medicine and Palliative Care at the Beth Israel Medical Center in New York, has since expressed regret for his evangelism on behalf of opioids.
He was “trying to create a narrative so that the primary care audience would ... feel more comfortable about opioids,” Portenoy said in a 2010 interview with Andrew Kolodny, the chief of a group seeking to rein in drug use, Physicians for Responsible Opioid Prescribing. “Because the primary goal was to destigmatize opioids, we often left evidence behind. ...
“To the extent that some of the adverse outcomes now are as bad as they have become in terms of endemic occurrences of addiction and unintentional overdose deaths, it’s quite scary to think about how the growth in that prescribing driven by people like me led in part to that occurring.”
Through a spokesman, Portenoy declined to comment for this report, but he has said that he continues to believe that many patients with chronic pain can benefit from opioids.
James Heins, a Purdue spokesman, said that “it is implausible that our marketing caused an upsurge in overall prescriptions of opioids or in the incidence of abuse,” because the company commands only a small portion of the painkiller market.
Moreover, he said, the notion that the risk of addiction was small was “not based on studies funded by Purdue but rather on the larger body of medical literature and clinical experience.”
Even today, he said, it is difficult to say exactly how many people who are prescribed opioids become addicted.
In few places are the effects of the opioid epidemic clearer than in Portsmouth, a town on the Ohio River near Ohio’s borders with West Virginia and Kentucky. About 10 percent of babies here are born addicted to opioids. At one point, nine “pill mills” operated out of this region of 80,000 people. About 20 people a year die of drug overdoses. And last year, for every resident, more than 100 doses of opioids were prescribed and dispensed.
Ask someone here whether the risks of opioid addiction are minimal, and some snort or roll their eyes.
“Around here, we call it ‘pharmageddon,’ ” said Lisa Roberts, the public health nurse for the town, whose primary job is to reduce the fatalities associated with drug use. “This has been absolutely devastating to Appalachia. From what we’ve seen, the risks of addiction were tremendous.”
Early on in the use of the drug, officials at the Drug Enforcement Administration perceived the danger to patients.
“The company’s aggressive methods, calculated fueling of demand and the grasp for major market share very much exacerbated OxyContin’s widespread abuse and diversion,” a November 2003 memo from the agency said. “The claim in Purdue’s ‘educational’ video for physicians that opioid analgesics cause addiction in less than one percent of patients is not only unsubstantiated but also dangerous because it misleads prescribers.”
The FDA, which must approve drug labels, allowed Purdue to say on its label: “The development of addiction to opioid analgesics in properly managed patients with pain has been reported to be rare.”
The agency warned that drug abusers and addicts might try to obtain the drugs, but it indicated that the risks seemed minor for patients: “We do not know how often patients with continuing (chronic) pain become addicted to narcotics, but the risk has been reported to be small.”
The agency, however, would later change its mind.
By 2008, the claims that the risks of addiction in patients were small were removed from the OxyContin label, after “extensive negotiations” with Purdue, an FDA spokeswoman said.
“The labeling information, including language regarding addiction, has evolved over time as data has become available,” Morgan Liscinsky said.
The FDA did not say what evidence led the agency to allow the previous claims or what new findings led it to ask for the removal of those claims.