Oregon’s Opioid Tapering Plan Delayed

By Pat Anson, PNN Editor

A controversial plan that could force thousands of Medicaid patients in Oregon off opioid pain medication has been put on hold because of a medical expert’s potential conflict of interest.

Oregon Health Authority (OHA) Director Patrick Allen asked the Health Evidence Review Commission (HERC) to table a final vote on changes in opioid policy until his agency could get an independent review of the recommendations.

At issue is a task force plan to limit Medicaid coverage of opioids to just 90-days for fibromyalgia and lower back pain. Patients currently on opioids longer than 90 days would be required to taper off the medications and switch to alternative therapies such as acupuncture and physical therapy that would be covered by Medicaid.

The plan has drawn nationwide criticism from chronic pain patients, advocates and pain management experts who say forced tapering would “exacerbate suffering for thousands of patients.”

Allen said he learned this week that Dr. Catherine Livingston, a family medicine physician who serves as a contracted medical consultant to HERC, is also a paid consultant to the Kaiser Center for Health Research and the National Institute of Drug Abuse. Livingston helped draft the opioid coverage proposal.

“I have requested the HERC to remove a chronic pain management proposal from today’s agenda to allow OHA time to seek independent review to ensure no potential conflicts of interest compromised the way the chronic pain benefit proposal was developed for the HERC’s consideration,” Allen said in a statement.

“It is vital for the Oregon Health Plan to cover safe and effective therapies to help people reduce and manage chronic pain. Yet it is also vital that Oregonians have full confidence in the decisions the HERC makes to assess the effectiveness of health care procedures.”

No timetable was set for the independent review. At a HERC hearing earlier this week, The Bend Bulletin reported that state officials defended the opioid policy change.

“I think the potential harms associated with opioids have become clear,” said Dr. Dana Hargunani, chief medical officer for the Oregon Health Authority. “Harms shown by the evidence about tapering are less clear.”

But in a joint letter signed by over 100 pain management experts, Dr. Sean Mackey, chief of pain medicine at Stanford University, urged the commission not to mandate “non-consensual forced tapering.”

“We fear the HERC’s proposal is, in essence, a large-scale experiment on medically, psychologically and economically vulnerable Oregonians, at a moment when Oregon has already seen a significant reduction in opioid prescribing and prescription opioid-related deaths,” Mackey wrote. “The evidence supports that this proposal represents an alarming step backward in the delivery of patient-centered pain care for the state of Oregon.”

Other members of the task force questioned the distinction between forced and voluntary tapers.

“I can’t tell you whether the tapers I do in my practice are voluntary or involuntary,” said Dr. Roger Chou, a professor of medicine at Oregon Health & Science University who was one of the co-authors of the controversial CDC opioid prescribing guideline.  “I explain why I think that’s important, that it’s a safety issue, and I guide them through the process. I try to be empathetic, but they don’t want to taper.

“I don’t think there’s anything compassionate about leaving people on drugs that could potentially harm them.”

Steep Decline in New Opioid Prescriptions

By Pat Anson, PNN Editor

The number of doctors writing new prescriptions for opioid pain medication has fallen by nearly a third in recent years, according to a large but limited study that documents a dramatic shift in opioid prescribing patterns in the U.S.

Researchers at Harvard Medical School studied health data for over 86 million patients insured by Blue Cross Blue Shield from 2012 to 2017, and found that first-time prescriptions for patients new to opioids – known as “opioid naïve” patients -- declined by 54 percent.

At the start of the study, 1.63% of Blue Cross Blue Shield patients were being treated with new opioid prescriptions. Five years later, only 0.75% were.

The study also found a shrinking pool of doctors willing to start opioid treatment. The number of doctors who prescribed opioids for opioid naive patients decreased by nearly 30 percent, from 114,043 to 80,462 providers.

The research findings, published in The New England Journal of Medicine, do not provide any context on the patients’ health conditions or the severity of their pain and injuries. As such, it is a data-mining study that provides no real information on the harms or benefits of opioids.

"The challenge we have in front of us is nothing short of intricate: Curbing the opioid epidemic while ensuring that we appropriately treat pain," lead investigator Nicole Maestas, PhD, an associate professor of health care policy at Harvard Medical School, said in a statement. "It's a question of balancing the justified use of potent pain medications against the risk for opioid misuse and abuse."

First-time prescriptions for opioids are usually used to treat short-term acute pain caused by trauma, accidents or surgery. They rarely result in long-term opioid use or addiction, but have become a major target for healthcare policymakers and anti-opioid activists. Several states have adopted regulations that limit the initial supply of opioids to 7 days or less.

While the number of doctors starting opioid therapy has fallen dramatically, Harvard researchers say many are still engaged in “high-risk prescribing” – which they defined as new prescriptions for more than 3 days’ supply or a daily dose that exceeds 50 morphine milligram equivalent (MME).

More than 115,000 of these “high-risk prescriptions” were written monthly for Blue Cross Blue Shield patients. Over 7,700 of the prescriptions exceeded 90 MME per day, a dose that researchers say puts patients at a substantially higher risk of an overdose. The study did not identify whether any of those high-dose patients experienced an overdose.

Opioid prescriptions in the U.S. have fallen sharply since their peak in 2010, but have yet to slow the rising tide of overdoses. Nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl and heroin, not prescription opioids.

Risky Combination: Opioids and Gabapentin

By Pat Anson, PNN Editor

Opioid medication significantly reduces low back pain, but opioids should not be used in combination with gabapentin (Neurontin) because of their limited effectiveness and potential for abuse, according to the authors of a small new study presented at the annual meeting of the American Academy of Pain Medicine.

"In these days, when we are focusing on reduction of opioids due to opioid crisis in the U.S., gabapentin could be an important part of multimodal non-opioid pain management," N. Nick Knezevic, MD, of the University of Illinois in Chicago told MedPage Today. "However, it should not be given to all patients since the effectiveness in chronic pain patients, particularly in those with low back pain, is limited."

KAISER HEALTH NEWS

In a retrospective study, Knezevic and his colleagues looked at 156 patients with low back pain; half of whom were treated with opioids alone and the other half with a combination of opioids and gabapentin.

“According to our study, the combination of gabapentin with opioids was not statistically superior in providing pain relief, in contrast to opioids alone, in patients with chronic pain. Our results are in line with recent guidelines for low back pain treatment that reflect the need to assess the recommendation of gabapentinoids for chronic pain in patients already taking opiods to mitigate risk factors of abuse and overdose,” researchers found.

Gabapentin is an anticonvulsant that was originally developed as a treatment for epilepsy, but is now widely prescribed for a variety of chronic pain conditions. Its use in primary care as a treatment for chronic back and neck pain has risen by 535% in the last decade, despite little evidence of its effectiveness.

"The fact that anticonvulsants are often advertised to be effective for 'nerve pain' may mislead the prescriber to assume efficacy for low back pain or sciatica," Oliver Enke, MD, of the University of Sydney, told MedPage.

A 2018 study by Australian researchers found that gabapentinoids did not reduce back pain or disability and often had side effects such as drowsiness, dizziness and nausea. Another recent study found that combining gabapentin with opioid medication significantly raises the risk of dying from an overdose than opioid use alone.

There have been increasing reports of gabapentin being abused by drug addicts, who have learned they can use the medications to heighten the high from heroin, marijuana, cocaine and other substances.

The CDC’s opioid prescribing guideline recommends gabapentin as a safer alternative to opioids, without saying a word about its potential for abuse or side effects.

A 2017 commentary in the The New England Journal of Medicine warned that gabapentinoids -- a class of nerve medication that includes both gabapentin and pregabalin (Lyrica) -- are being overprescribed.

"We believe… that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic,” wrote Christopher Goodman, MD, and Allan Brett, MD. “We suspect that clinicians who are desperate for alternatives to opioids have lowered their threshold for prescribing gabapentinoids to patients with various types of acute, subacute, and chronic noncancer pain."

60 Minutes Fails to Consider Pain Patients

By Laura Mills, Kate M. Nicholson, and Lindsay Baran

In a Feb. 24 segment, CBS’s 60 Minutes accused the Food and Drug Administration (FDA) of igniting the overdose epidemic in the United States with its “illegal approval of opioids for the treatment of chronic pain.” While the program highlighted the adverse consequences of misleading pharmaceutical marketing and lax government oversight, this segment failed to consider the perspective of patients who legitimately use opioids for pain, stigmatized them as drug-seekers, and propagated misconceptions about the overdose crisis, such as the idea that opioid treatment for chronic pain is indisputably illegitimate and is driving overdose deaths in the U.S.

When OxyContin went to market in 1996, its FDA label said that addiction was “very rare” when the medication was used to manage chronic pain. Although that warning was enhanced in 2001, the market for OxyContin was already booming: advertising spending for the drug increased from $700,000 in 1996 to $4.6 million in 2001. Lawsuits allege that Purdue Pharma, the maker of the drug, targeted high-prescribing physicians and continued to aggressively market OxyContin even after it learned its product had become a go-to drug for illicit use. The lack of government oversight and Purdue’s practices certainly deserve media scrutiny that could help shed light on actions that may underlie the overdose crisis.

However, the guests featured in the 60 Minutes segment gave the impression that the use of opioids for chronic pain is illegitimate or illegal, that prescription opioids are still driving overdose deaths in the United States, and that the use of prescribed opioids to manage chronic pain is equivalent to “heroin addiction.”

These are false narratives that do real harm to pain patients, who have been regularly stigmatized in the media and elsewhere as drug-seekers. In presenting this report, 60 Minutes failed to tell the other side of the story: that of pain patients who rely on these medications to function, and that of the medical community which largely agrees that opioids may help patients whose pain isn’t resolved by other means.

Chronic pain is a large category that includes pain associated with incurable illnesses, severe neurological conditions, and catastrophic trauma as well as more common ailments like arthritis. There is growing agreement that using opioids across this broad category was inappropriate and did harm, and that it is important to balance the potential benefits of opioids with misuse and diversion risks. But the medical community still largely agrees that, for some patients, opioids provide benefits. Indeed, the Centers for Disease Control, the Federation of State Medical Boards, a 2011 report by the Institute of Medicine, and all applicable medical and government guidelines on prescribing opioids have reaffirmed that opioids may be appropriate for patients whose chronic pain isn’t resolved by other means. 

Re-evaluating the use of opioids in long-term pain makes sense given recent history, but rushing to judgment before we do so can do real harm and risks violating a fundamental component of the right to health, including the right to adequate treatment for pain.  In over 80 interviews with patients, physicians, and experts, a recent Human Rights Watch report found a disconcerting trend: chronic pain patients are being forced off opioid medications simply because doctors fear regulatory oversight and reprisal. In many cases, physicians acted against their better medical judgment. Even when they believed their patients’ health was improved by long-term opioid treatment, they felt they had no option but to reduce patients’ doses dramatically or cut them off completely. They felt a wide range of pressures, from fear of Drug Enforcement Agency or state medical board scrutiny to the heavy bureaucratic burden created by insurance companies through their efforts to discourage opioid prescribing.

When deprived of their medication, the consequences for patients can be devastating: their health declines to the point where they can no longer work, do simple chores, or take care of their personal hygiene.  Several patients said they had turned to alcohol or illicit drugs to manage their pain when they were deprived of care.

Take Maria Higginbotham, whose story is included in the report. She has undergone 12 operations to prevent the collapse of her spine. Unfortunately these operations, which failed to relieve her pain, also left her with adhesive arachnoiditis, an incredibly painful condition that causes the nerves of the spinal cord to “stick together.”

“Re-evaluating the use of opioids in long-term pain makes sense given recent history, but rushing to judgment before we do so can do real harm and risks violating a fundamental component of the right to health.”

— Human Rights Watch

Maria is now being forced to a lower dose of medication by a provider who believes she needs opioids, but is afraid of attracting law enforcement scrutiny of his practice. Previously, Maria could function independently; she now requires assistance to go to the toilet.  To suggest that Maria has no legitimate right to these medications—and that her need for them is misguided, inappropriate or the result of drug misuse — is stigmatizing to all patients like her.

Hundreds of leading physicians and experts from with varying views on the efficacy of opioids have called attention to the dangers of involuntarily discontinuing opioids for the estimated 18 million Americans who currently use them for long-term pain, a practice the CDC and other medical bodies do not encourage. These dangers include medical destabilization, the lost ability to work and function, and suicide. The National Council on Independent Living (NCIL), a national disability rights organization, shares these concerns, which have a disproportionate impact on people with disabilities living with chronic pain who already face major barriers to accessing healthcare.  The American Medical Association has similarly criticized the indiscriminate discontinuation of opioids, and has underscored that the stigma surrounding opioids now affects cancer and palliative care patients who, despite explicit exemptions, face increased barriers to access as well. 

While liberal prescribing undoubtedly caused harm, further perpetuating inflammatory and stigmatizing ideas about people who rely on opioids helps legitimize the growing reluctance of physicians to prescribe these medications to those who they believe need them. At a time when the prescribing of opioids has dropped precipitously and drug overdose deaths are largely attributed to illicit substances, such harm ought to figure into the conversation.

It’s true that there is a lack of high quality data studying the efficacy of opioids beyond 12 weeks, but it is also the case that most medications approved for the treatment of pain reflect studies of similar duration.  This is in part because doing long-term, placebo-controlled trials with real human beings who are suffering presents practical and ethical challenges. 

FDA Commissioner Scott Gottlieb recently responded to the concerns raised by 60 Minutes, by announcing that the agency will conduct new studies into the efficacy of opioid analgesics for chronic pain, a move that he signaled could have an impact on how these drugs are marketed in the future. We agree that more research is critical and have backed initiatives such as the National Pain Strategy that call for much needed additional research into chronic pain. In the meantime, the dangers of reinforcing an incomplete or incorrect narrative and of stigmatizing patients are real—60 Minutes should ensure it doesn’t do either in its coverage, and should show all sides of the story.

This article was originally published on the Human Rights Watch website and is republished with permission.   

Laura Mills is a health researcher at Human Rights Watch and author of the HRW report, “Chronic Pain, the Overdose Crisis, and Unintended Harms in the U.S.”

Kate M. Nicholson is a civil rights and health policy attorney. She served for 20 years in the Department of Justice’s civil rights division, where she drafted current regulations under the Americans With Disabilities Act. She gave a TEDx talk about chronic pain, “What We Lose When We Undertreat Pain.”

Lindsay Baran is the policy analyst at the National Council on Independent Living (NCIL), the longest-running national cross-disability grassroots organization run by and for people with disabilities.

FDA Commissioner Resigns Unexpectedly

By Pat Anson, PNN Editor

The head of the U.S. Food and Drug Administration resigned unexpectedly Tuesday, just days after a critical report on 60 Minutes that alleged the FDA “opened the floodgates” to the opioid crisis.  

“I’m immensely grateful for the opportunity to help lead this wonderful agency,” FDA commissioner Scott Gottlieb, MD, tweeted. ”This has been a wonderful journey and parting is very hard.”

In a lengthier statement to FDA staff, Gottlieb cited family reasons for his departure.

“There’s perhaps nothing that could pull me away from this role other than the challenge of being apart from my family for these past two years and missing my wife and three young children,” Gottlieb said, indicating he would remain on the job until next month.

Gottlieb is a 46-year old cancer survivor and a former consultant to several drug companies. He commutes to Washington DC from his home in Westbury, Connecticut, where he lives with his wife and three daughters.   

President Trump tweeted that Gottlieb “has done an absolutely terrific job” and “he and his talents would be greatly missed!”

SCOTT GOTTLIEB, MD

There was no indication that Gottlieb was in trouble or that he was forced out. The FDA is currently involved in a number of complex and controversial regulatory issues, from high drug prices and e-cigarettes to medical marijuana and the opioid crisis.

The timing of Gottlieb’s departure is puzzling, however, because he tweeted two months ago that he had no intention of resigning after hearing from friends about speculation in the news media that he was leaving.

“I want to be very clear — I’m not leaving. We’ve got a lot of important policy we’ll advance this year,” Gottlieb tweeted, adding a famous quote from Mark Twain that reports of his death “have been greatly exaggerated.”

The 60 Minutes report alleged that the FDA caved into lobbying pressure from the pharmaceutical industry in 2001 by changing the warning labels on OxyContin and other opioid medications to indicate they were effective for long term use.

Gottlieb was not working at FDA when the agency made its labeling decision, but pledged last week in a lengthy essay that the FDA would “learn from past mistakes” and take “a much more aggressive approach to regulatory action” involving opioids.

Gottlieb joins a long list of agency directors and cabinet members who have resigned from the Trump administration, including former Health and Human Services Secretary Tom Price, who was forced out over excessive travel expenses and other ethical lapses, and former CDC director Brenda Fitzgerald, who resigned after it was disclosed she invested in tobacco and drug companies.

How Has CDC Opioid Guideline Affected You?

By Lynn Webster, MD, PNN Colomunist

The controversial CDC Guideline for Prescribing Opioids for Chronic Pain was released on March 15, 2016 in an effort to curb the opioid crisis. While “largely supportive” of the guideline at the time, the American Medical Association had concerns about how it would be implemented.

“We remain concerned about the evidence base informing some of the recommendations; conflicts with existing state laws and product labeling; and possible unintended consequences associated with implementation, which includes access and insurance coverage limitations for non-pharmacologic treatments, especially comprehensive care; and the potential effects of strict dosage and duration limits on patient care,” said Patrice Harris, MD, then board chair-elect of the AMA.

Dr. Harris proved to be prescient. In the last three years, insurance companies, healthcare systems and dozens of states have imposed limits – based on the CDC guideline -- on the quantity and dose of opioids dispensed to people with pain.

Oregon has even drafted a plan to stop opioid prescribing for many Medicaid patients and require that they use alternative treatments. Here was my response to Oregon's plan, in which I warned that “forcing opioid tapers is not an appropriate or compassionate solution” and could drive some patients to suicide.

Pharmacies are also imposing limits. In 2017, CVS announced it would limit the number of pills for new patients with acute pain to 7 days’ supply, saying “the CDC Guideline should become the default approach to prescribing opiates.”

That same year, the giant prescription benefits manager Express Scripts also started limiting new opioid prescriptions and set a dosage limit “based on CDC prescribing guidelines.” 

This January, the Centers for Medicare and Medicaid Services made it more difficult for over a million Medicare patients to receive doses above 90 MME (morphine milligram equivalent) which they consider a high dose. CMS also imposed a seven-day limit on all patients receiving a new opioid prescription. The CMS rules are based on evidence “cited in the CDC Guideline.”  

‘Revisit This Guideline’

When it first published its recommendations, CDC pledged to “revisit this guideline as new evidence becomes available” and said it was “committed to evaluating the guideline to identify the impact of the recommendations on clinician and patient outcomes, both intended and unintended, and revising the recommendations in future updates when warranted.” 

In a recent statement to PNN, the CDC said there are “several studies underway with external researchers” evaluating the impact of its guideline on opioid prescribing and patient outcomes. The agency also said it recently commissioned a review by Agency for Healthcare Research & Quality (AHRQ) “to determine what new scientific evidence has been released” on the effectiveness of opioid and non-opioid pain relievers.

In the meantime, no revision of the guideline is being planned.    

The CDC guideline was well-intentioned and included many wise principles of opioid prescribing. But it appears to be more about limiting the supply of opioids than improving clinical care for pain patients. Limiting opioid access may be good for some patients, but for many it means more pain and a worsened quality of life.  

There is little evidence that limiting supply reduces opioid addiction and overdoses. Opioid prescribing in the United States has significantly declined since 2012, yet opioid overdoses continue rising – primarily due to illicit fentanyl, heroin and counterfeit drugs, not prescription opioids. The CDC's reevaluation of the guideline should take this into consideration.  

In 2018, the National Institutes of Health’s Interagency Pain Research Coordinating Committee recommended that the CDC "engage with advocates and patients, who have been negatively impacted by the unintended consequences of the CDC guideline." It also called on the FDA and the CDC to work together to "update and improve" the guideline.  

Rather than seeing the CDC guideline as a resource or helpful tool, many prescribers live in fear of it. The DEA now routinely monitors prescription drug databases, looking for “red flags” that indicate a doctor is prescribing opioids at doses above those recommended by the CDC. The AMA last year took a stand against this “inappropriate use” of the guideline, and passed a resolution stating that doctors should not be subject to criminal prosecution or other penalties solely for prescribing opioids at higher dosages.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is a former president of the American Academy of Pain Medicine and the author of “The Painful Truth.”

You can find Lynn on Twitter: @LynnRWebsterMD. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Future Pain Pills

By Roger Chriss, PNN Columnist

The Food and Drug Administration announced this week that it would require drug makers to conduct new studies on the effectiveness of opioid pain medication and whether long-term use of the drugs lead to addiction. The FDA’s unprecedented action was due in no small part to a 60 Minutes report that said the agency “opened the floodgates” to the opioid crisis by approving the use of opioids for chronic pain. 

With opioid medication coming under scrutiny again – and perhaps more regulatory action – this is a good time to assess where we stand with development of newer and safer painkillers.  

Many analgesics already on the market have too many risks or too few benefits. A recent meta-analysis in JAMA concluded that opioids “may provide benefit for chronic noncancer pain, but the magnitude is likely to be small.”

And a new Cochrane review on acetaminophen (Tylenol) for hip or knee osteoarthritis found “only minimal improvements in pain and function.”

So new analgesics, whether safer opioids or non-opioid drugs, are urgently needed. Fortunately, there has been significant progress.

NKTR-181, from Nektar Therapeutics, is a new kind of opioid under “fast track” FDA review. It was designed with safety in mind, because it enters the nervous system slowly as a result of its unique chemical structure. NKTR-181 is the only abuse-deterrent opioid in the drug development pipeline designed to reduce the “high” and “drug liking” that can lead to addiction. Practical Pain Management recently gave it four out of five stars as a future analgesic.

Desmetramadol, from Syntrix Pharmaceuticals, is another opioid in early testing. Developed with support from the National Institute on Drug Abuse, desmetramadol is designed as a safer version of tramadol, a Schedule IV opioid. Researchers are looking at the results of a recent clinical trial to see whether the new drug “provides the safety and pain relief of tramadol without its metabolic issues.”

VX-150, from Vertex Pharmaceuticals, is a sodium channel inhibitor that late last year finished a “proof-of-concept” Phase II trial successfully. It acts specifically on sodium channels to block the pain caused by small fiber neuropathy. Because these channels are not expressed in the brain, VX-150 should have few if any cognitive side effects. Phase III clinical trials are expected to start later this year.

Tanezumab, from Pfizer and Eli Lilly, just completed a Phase III clinical study for chronic low back pain. The results showed that tanezumab injections were associated with a statistically significant improvement in low back pain compared with placebo. Tanezumab is also being studied as a treatment for osteoarthritis, although there are some lingering concerns about its side-effects.

Finally, the novel compound AT-121 from Astraea Therapeutics is showing promise as a non-addictive opioid analgesic. Researchers created AT-121 to bind to both the mu opioid receptor and the FQ peptide receptor, a combination that blocks the unwanted side effects of current opioid analgesics. Preclinical testing of AT-121 in animals found that it was more potent than morphine, but did not produce physical dependence or tolerance at high doses. The National Institute on Drug Abuse recently called AT-121 a “promising alternative to opioid pain medications.”

Improved understanding of the nervous system and of chronic painful disorders is also contributing to drug development. A recent review in Frontiers in Pharmacology looks at emerging “safer opioids” that provide effective pain relief with fewer side effects. The review explains that the new goal of drug developers is to target opioid receptors in injured or diseased tissues, while avoiding the brain to reduce cognitive side effects and minimize risk of abuse, addiction and overdose.

And new genetic research is identifying genes involved in painful neuropathies. For instance, a recent case report found that a variant in the gene PMP22 is linked to painful peripheral neuropathy in Charcot-Marie-Tooth Disease.

With the prevalence of chronic pain increasing as the population ages, the development of safer, more effective analgesics is critical. Advances in drug development techniques and better understanding of painful disorders should accelerate the process.  

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Counterfeit Pill Lab Exposed in BBC Report

By Pat Anson, PNN Editor

Counterfeit prescription drugs have emerged as a worldwide problem – from fake “Mexican Oxy” sold in United States to bogus cancer drugs recently found in Turkey, Argentina and Switzerland.

This week a chilling BBC documentary took viewers inside a dingy underground lab in the UK where counterfeit Xanax pills are made – often laced with illicit fentanyl and other dangerous chemicals.

One dealer bragged to BBC reporter Livvy Haydock that he could make 42,000 Xanax pills in three hours.

"I import the raw ingredients and chemicals needed and then I press the tablets with a tablet press machine,” he said.

"I've been doing this for many years and I've never been at the point where I can produce and supply enough to meet the demand for my product. I'm always turning away customers.”

BBC ‘INSIDE BRITAIN’S BLACK MARKET”

The fake anti-anxiety pills are manufactured in a converted cement mixer and tested on volunteer “guinea pigs” before being sold on the street, often to teenagers.

"They're taking that risk, they're paying the money. I'll make it and I'll do it as best as I can and I'll give a good service and provide a good product and the rest is on them," the dealer said.

He boasted that overworked customs officials send him warning letters when his shipments are seized, but they rarely tell police.

"I've had plenty of packages stopped from customs to addresses. A lot of the time you just receive a letter saying it's been seized,” he explained. “"They don't really follow it up. Sometimes they do, but the majority of the time they don't.”

A similar problem exists in the United States, where the Postal Service processes and delivers nearly half of the world’s mail. Postal inspectors can’t even open suspicious packages without a search warrant.

“Drug traffickers have familiarized themselves with and exploited vulnerabilities in the Postal Service network,” a recent Inspector General report warned. “Individuals can now order nearly any type of illicit drug online and have it delivered to a location of their choosing, all from the comfort of their own home.

“These illicit purchases often rely on mail shipment companies, including the Postal Service, to deliver products to customers as they provide greater opportunities for anonymity than other delivery options, such as human couriers.”

The Inspector General recommended that Congress pass legislation to give postal inspectors legal authorization to open and inspect domestic packages suspected of carrying illicit drugs.

According to the World Health Organization, the counterfeit drug market is worth $200 billion worldwide, with almost half of the fake and low-quality medicines sold in Africa. Up to 300,000 people may die from pneumonia and malaria every year due to substandard medications primarily made in China, India, Pakistan and the United Kingdom.

Prevalence of Chronic Pain Increasing

By Lynn Webster, MD, PNN Columnist

According to the Centers for Disease Control and Prevention, opioid prescribing quadrupled from 1999 to 2010. Some policymakers suggest that the amount prescribed in 1999 was appropriate and should remain static, and that any prescribing above the 1999 level exceeds the amount required to meet the needs of people in pain.

Perhaps, but it is important to understand that pain was vastly undertreated in the 1990s and there was a clear need to find effective treatment for pain patients. At least some of the increase in opioid prescribing would also seem logical, based on the greater number of people in pain.

According to the National Institutes of Health (NIH), the number of American adults suffering from at least one painful condition increased substantially from 120.2 million in 1997 to 178 million in 2014 – about 41 percent of the adult population. These numbers are from a comprehensive analysis of 18-year trends in the rates of noncancer pain, recently published in the Journal of Pain. 

 Aging Population

The NIH report may make you wonder why there are more people in pain now than there were in 1999. Here are some possible explanations.

Our aging population includes an ever-increasing number of elderly people. Baby boomers, who make up the largest demographic of society, recently began to enter their 70s. That is the decade during which we begin to experience a much greater prevalence of arthritis, spinal pain, obesity, surgical operations and cancer.

Mortality rates for cancer continue to decline, thanks to better treatments. More than 40% of cancer survivors now live longer than 10 years. That is good, of course, but many cancer survivors experience treatment-related chronic pain. 

Aging increases the likelihood that people will experience chronic pain. More than half of all adults older than 65 experience arthritic pain of the spine and other joints. For more age-related statistics regarding arthritis, click on this U.S. government PubMed abstract, the CDC's arthritis information page or the Arthritis Foundation’s website.  

In all age groups, the U.S. has an obesity epidemic (according to the CDC and the Journal of the American Medical Association) which can lead to diabetes. Obesity causes increased load on the back and joints, causing chronic pain. In addition, more people have peripheral neuropathy caused by diabetes. 

Finally, there is the problem of chronic post-surgical pain, which we began to recognize around the turn of the century. The incidence of chronic pain after major surgery is estimated to lie between 20% and 50%. Relatively minor operations, such as inguinal hernia repair or a C-section, seem to lead to this problem in approximately 10% of patients. This is an annuity that will keep growing as more operations occur every year.  

The increased prevalence of chronic pain has probably contributed to a greater number of opioid prescriptions. In addition, we have historically failed to recognize that pain deserves to be treated.

Alternative therapies like massage and acupuncture have not been widely available due to lack of insurance coverage. Thus, many people in chronic pain have not had access to any therapy except opioids. This can partially explain why there was an increase in the amount of opioids prescribed from 2001 to 2014.  

Undertreated Pain

Quadrupling the amount of opioids prescribed over several decades may sound excessive, unless we consider the growing number of people who were undertreated and in severe pain, year after year.  

Additionally, we must recognize opioids have not been distributed equally. It is possible that more opioids have been prescribed than appropriate for some patient populations, while other patients have been denied access to any pain treatment. 

A major shift in opioid prescribing began several years ago and by all accounts is accelerating. Between 2013 and 2017, the amount of opioids prescribed declined by 22%. The people most affected by the decrease appear to be those who reported benefit from opioid therapy.  

The amount of opioids that should be prescribed will remain open to debate. But millions of Americans have been -- and continue to be -- denied access to pain treatment, and there should be no debate about the fact that failure to treat severe pain is unacceptable.   

Everyone in the health care system and policymakers should be concerned about the NIH report on the prevalence of chronic pain. The dramatic increase in the number of people with chronic pain warrants our examination of all polices and resources to ensure that this population is receiving the care they need and deserve.  

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is a former president of the American Academy of Pain Medicine and the author of “The Painful Truth.”

You can find Lynn on Twitter: @LynnRWebsterMD. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Do Rx Opioids Really Increase Risk of Fatal Accidents?

By Pat Anson, PNN Editor

A recent study published in JAMA Network Open made headlines when it claimed that use of prescription opioids more than doubled the risk of causing a fatal car accident.  

Researchers at Columbia University Mailman School of Public Health looked at death certificates and toxicology tests on drivers involved in over 18,000 fatal two-vehicle accidents from 1993 to 2016. They found that 1,467 of the “crash initiators” tested positive for hydrocodone, morphine, oxycodone or other prescription opioids.    

The researchers reported their findings as “compelling evidence that use of prescription opioids by drivers is a significant contributing factor” in fatal crashes, which was a dog whistle for media outlets like CNN to warn, “Opioid epidemic spilling over onto roads.”

It turns out the evidence was not so compelling after all.

Like many states, Maryland faces growing rates of opioid abuse and addiction. But when researchers looked at opioid-related crashes in Maryland from 2006 to 2017, they found no significant increase in fatal accidents.

“The fact that opioid crashes in Maryland over the last 10 years have been more or less steady was a surprise,” Johnathon Ehsani, PhD, a professor at the Johns Hopkins Bloomberg School of Public Health told The Washington Post.

“That is striking, because Maryland is one of those states that has been quite severely affected by the overall opioid epidemic.”

Ehsani and his colleagues took another look at the toxicology data and realized it was misleading. The reason was simple: Because hospitals and first responders often give opioid medication to patients injured in accidents, autopsies will detect those opioids in patients who later die from their injuries. In other words, the drivers may not have been under the influence of opioids before the crash.

When researchers only looked at a sub-sample of drivers who died at the scene, they found that the use of prescription opioids was “considerably lower than those who died hours or days following the crash.”

“We applied a stricter definition than our other colleagues did,” said Ehsani, who published his findings in the less prominent journal Accident Analysis & Prevention. “We were more conservative in our case definition.”

The JAMA study apparently over-counted the number of opioid-related crashes by not differentiating between drivers who died at the scene and those who died after getting medical treatment with opioids.

"When determining the prevalence of opioid use in a population, it can be tricky to untangle the two circumstances," says Ehsani. "Thinking differently about the way in which researchers count cases has implications that can offer policymakers and public health professionals more meaningful results."

No one is suggesting that it’s okay to drive a vehicle while impaired by opioids. But it’s also not okay for researchers and prominent medical journals to use flawed data to suggest that patients using prescription opioids are more likely to cause fatal accidents.

In Maryland, they found just the opposite may be true.

“It could be that a number of people who are impaired by opioids choose not to drive,” Ehsani said. “It could be that there is some self-selection going on in that population or it could be that some of those who are most seriously impaired are unable to or don’t have access to a vehicle to drive.”

Should the CDC Opioid Guideline Be Revised?

By Pat Anson, PNN Editor

Carol Levy’s recent column (see “Guideline Paranoia”) drew quite a response from PNN readers, many of them offended by Carol’s contention that pain sufferers complain too often about the CDC’s 2016 opioid prescribing guideline.

“Maybe if we did not take any and all new guidelines as a frontal attack on us, maybe we would not be seen and referenced so often as a major component and cause of the opioid epidemic,” Carol wrote.

Those were fighting words to many pain sufferers who’ve been cutoff from opioid medication or had their dose reduced since the guideline came out. Dozens of patients commented on Carol’s column.

“Sounds a bit like blaming the victim for getting upset,” said Jen Saeger. “We ARE being targeted and having our medication taken away because these CDC guidelines have been taken as law. This isn’t overreacting, this is happening all over the country.”

“This woman needs to be educated about what is actually happening. We aren't overacting,” said Teresa. “Does she not know pain patients are being tapered or have completely lost their pain meds? Has she not heard of the suicides that are occurring in the chronic pain community?”

“Once these guidelines were released my pain doctor cut my medications by nearly 50% as well as many of his other chronic pain patients. He also showed me a letter from the CDC exclaiming that he was writing too many prescriptions for narcotic pain killers,” said Joe Allio. “So when they say this was a suggested guideline and not a mandate, IT'S A BIG FAT LIE!!!!! What I saw in this letter was nothing short of a threat!”

“The policymakers are the ones that need to be reminded that these are just guidelines,” wrote Vickie Tway. “You might especially want to let the DEA know this as they are running roughshod over physicians and causing those who DO want to help intractable pain patients to give up their profession for fear of being raided and facing criminal charges for doing their jobs.”

“The problem is that (doctors), pharmacies and insurance companies are using those said guidelines against chronic pain patients. Whether that's who they were intended for or not. CPP are having their meds cut back or cut off because of this hysteria and the new guidelines,” said Tracey Morales. “Until the CDC makes a statement to set this right people are going to continue suffering.”

CDC ‘Committed to Evaluating the Guideline’

PNN readers are better informed and more knowledgeable about the CDC guideline than most Americans. And they’re right when they say that the guideline was only supposed to promote a dialogue between primary care physicians and patients about the risks of opioid therapy.  The recommendations were never meant to be mandatory rules for everyone to follow, yet they’ve been widely adopted by other federal agencies, states, insurers, pharmacies and throughout the U.S. healthcare system.

Within months of the guideline’s release, CDC was warned by its own public relations consultants that “some doctors are following these guidelines as strict law” and that “pain patients who have relied on these drugs for years are now left with little to no pain management.”

In a joint letter to the CDC last year, over 200 healthcare providers warned the agency that many patients were being abandoned or forcibly tapered off opioids, and some were turning to suicide or illegal drugs to escape from their pain.

“Within a year of Guideline publication, there was evidence of widespread misapplication of some of the Guideline recommendations,” the letter warns. “These actions have led many health care providers to perceive a significant category of vulnerable patients as institutional and professional liabilities to be contained or eliminated, rather than as people needing care.”

The CDC pledged three years ago to “revisit this guideline as new evidence becomes available.”

“CDC is committed to evaluating the guideline to identify the impact of the recommendations on clinician and patient outcomes, both intended and unintended, and revising the recommendations in future updates when warranted.”

Will the CDC keep its pledge? The agency did not immediately respond to a request for comment on what it was doing to assess the impact of guideline or whether it would be revised.

(Update: On February 28th — 9 days after we asked — the CDC sent PNN a brief statement indicating it has “several studies underway with external researchers” evaluating the impact of the guideline on opioid prescribing and patient outcomes.

“CDC is commissioning a chronic pain systematic review by the Agency for Healthcare Research & Quality (AHRQ) to determine what new scientific evidence has been released since the CDC Guideline was released in March 2016. The chronic pain systematic review is underway now,” said CDC spokesperson Courtney Lenard.

“The review will evaluate the effectiveness and comparative effectiveness of non-opioid pharmacologic therapy and pharmacologic (opioid and non-opioid) therapy for chronic pain, considering the effects on pain, function, quality of life, and adverse events.”

The statement gave no indication when the review and other studies would be completed.)

How has the guideline affected you and should it be revised? If you’re a patient or healthcare provider, you can help shape the debate by taking our survey. Either click here or on the banner above.

We’ll release the survey results on March 15th, the third anniversary of the guideline’s release.   

CDC: Opioid Prescriptions Drop in 3 of 4 U.S. Counties

By Pat Anson, PNN Editor

The Centers for Disease Control and Prevention has released another study documenting how prescriptions for opioid medication have fallen dramatically in recent years. The study partially credits the CDC’s own guideline for the drop in opioid prescribing, but makes no mention of the suffering and suicides of pain patients who’ve been cut off from opioid medication.

Researchers at the CDC’s National Center for Injury Prevention and Control – which developed the agency’s controversial 2016 guideline -- looked at opioid prescribing trends nationally from 2015 to 2017.

They found significant declines in high dose opioid prescribing and in the average daily dose, which fell from 48.1 MME (morphine milligram equivalent) to 45.2 MME, a 6% decline. The guideline recommends that doses not exceed 90 MME except in rare instances.

Nearly 3 out of 4 counties experienced a reduction of 10% or more in the amount of opioids prescribed – the counties colored green in the map below. Relatively few counties, primarily in the Midwest and northern Rockies, had a 10% or more increase in opioid prescribing – counties that are marked in orange.

JAMA INTERNAL MEDICINE

“The reduction in opioid prescribing that began in 2012 has accelerated in the United States. The amount of opioids prescribed decreased an average of 10.0% annually with reductions in 74.7% of counties from 2015 to 2017,” CDC researchers reported in JAMA Internal Medicine.

“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. Despite reductions in prescribing, opioid overdose rates continue to increase and are driven largely by illicitly manufactured fentayl.”

A similar CDC study in 2018 also documented a decline in prescriptions, but made no effort to measure the guideline’s impact on patients and whether it had improved the quality of their pain care or worsened it.  There is only a brief acknowledgement that both studies are limited by “the inability to determine the appropriateness of opioid prescriptions” -- a belated and backhanded admission by the CDC that its guideline is built on the false premise that it knows what an appropriate dose is.

Had the CDC looked in its own Twitter feed touting the latest study, it could have found insight from patients on the guideline’s effect on the quality of pain care.

“Yea this is why my wife has been bedridden for over 2 YEARS now as her doctor does NOT BELIEVE in pain medication.  And when we call all the other practices in the area its more of the same response. Either we don't prescribe opioids or we don't take pain patients,” one poster wrote.

“Let's not forget skyrocketing suicide and patients turning to the streets for relief. Good job you now have a #OpioidCrisis of your own making,” another poster wrote.

“When the numbers of a drug are more meaningful than the human lives they help. So caught up in numerical reduction people who once had managed pain are forced to suffer or #SuicideDueToPain. I guess this makes you folks very proud, to kill off the disabled,” said another.

“And here we see the CDC touting what they think is a great thing. Ironically of course they are likely NOT tracking how many patients committed suicides after being forcibly tapered for no medical reason,” said Dave Wieland, a pain patient and advocate.

“And you can bet they are NOT tracking how many patients who had been able to work on their stable medication dosage, have now been forced to apply for disability after having their medication also taken away for no medical reason. Oh yea that's right the CDC doesn't care about those things.”

When the CDC released its guideline nearly 3 years ago, it pledged to “revisit this guideline as new evidence becomes available" and to evaluate its impact on doctors and patients.

How has the CDC guideline affected you? As the third anniversary of the guideline approaches, PNN is conducting a new survey of patients and healthcare providers. Is the guideline working as intended?

Click here to take the survey, which should only take a few minutes.

‘Mexican Oxy’ Flooding U.S. Black Market

By Pat Anson, PNN Editor

New York City police and DEA agents have announced the seizure of 20,000 counterfeit oxycodone pills made with illicit fentanyl. The pills, which have an estimated street value of $600,000, are blue in color and stamped “M” on one side and “30” on the other, making them virtually indistinguishable from prescription oxycodone.

The fentanyl pills are believed to have originated in Mexico. Known on the street as “Mexican Oxy,” the highly potent counterfeit pills are often cheaper and easier to obtain than pharmaceutical-grade oxycodone. Black market 30 mg oxycodone pills sell on the street for $9 to $30 each and are surfacing around the country.

“If you take prescription pills that did not come directly from a pharmacy, you are risking your life,” said New York City Special Narcotics Prosecutor Bridget Brennan. “Throughout New York City, we have seen a spate of cases involving tens of thousands of potentially lethal fentanyl pills masquerading as oxycodone.

“Just because black market pills have the same color and design as legitimate pills, it does not mean they are safe. The ingredients and potency are all unknown, and minuscule amounts of fentanyl can cause overdose or death. Consuming a counterfeit pill is akin to playing Russian Roulette.”

Overdose deaths in New York City are at record-high levels and fentanyl is involved in over half of them. Fentanyl is a synthetic opioid 50 to 100 times more potent than morphine. A customer accustomed to taking oxycodone would not necessarily have the tolerance to ingest illicit fentanyl without suffering an overdose.

DEA PHOTO

Fentanyl powder is typically produced by illicit labs in China and then smuggled into the U.S. through Mexico. The powder is transformed into tablets by pill presses purchased online and then sold by drug traffickers. Four arrests in New York were made in connection with the latest seizure.

“These arrests highlight a growing trend in illicit street drugs which increases the risk of drug overdose,” said DEA Special Agent in Charge Ray Donovan. “Traffickers are mass producing pseudo-pharmaceutical pills made of heroin, fentanyl and other illicit drugs in makeshift laboratories throughout New York City. These pills attract users because they are more convenient and less conspicuous; but users should beware because they are unregulated and lethal.”

Fentanyl Seizures at Mexican Border

Mexican Oxy is also blamed for a rash of overdoses in Arizona, where fentanyl deaths have tripled in recent years.

“It’s the worst I’ve seen in 30 years, this toll that it’s taken on families,” Doug Coleman, DEA Special Agent in Charge of Arizona told the Associated Press. “The crack (cocaine) crisis was not as bad.”  

Last month, the U.S. Border Patrol announced its biggest fentanyl seizure ever — over 250 pounds were found in a truckload of cucumbers at a border crossing in Nogales, Arizona.

Most of the fentanyl was in powder form and over two pounds were made up of pills. Together, they had the potential to kill millions of people.  

“Just because black market pills have the same color and design as legitimate pills, it does not mean they are safe.”

— Bridget Brennan, NYC Narcotics Prosecutor

Most of the fentanyl seized by law enforcement is found hidden inside vehicles at official border crossings around Nogales and San Diego, according to the AP. Smaller shipments of fentanyl are sent directly to the U.S. from China through the mail. The Postal Service’s Inspector General recently reported that over 90 percent of illegal online pharmacies use the mail to ship illicit drugs.

The Postal Service is prohibited from opening packages without a search warrant and is obligated to accept inbound international mail. This makes it more difficult for postal inspectors to identify and track packages suspected of containing illicit drugs. By comparison, private carriers are able to open and inspect packages and can track shipments from beginning to end.

The Inspector General recommended that Congress pass legislation that would give postal inspectors authorization to open and inspect domestic packages suspected of carrying illicit drugs.

FDA Warns Drug Distributor

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has sent a warning letter to a wholesale drug distributor rebuking the company for its handling of several tampering cases involving oxycodone and other medications.

The letter to the CEO of the McKesson Corporation involves incidents in 2016 when pharmacies notified the company about the tampering and theft of medications it had supplied them with.    

In one such case, a Rite Aid pharmacy in Michigan found that the seal to a bottle labeled as containing 100 tablets of oxycodone had been broken. Inside the bottle a pharmacist found 15 tablets of Aleve, a non-steroidal anti-inflammatory pain reliever.  Two other Rite Aid pharmacies also reported to the company that oxycodone bottles had been tampered with. McKesson investigated the reports and determined the tampering and thefts likely occurred while the bottles were in its possession.  

Similar tampering incidents involved drugs used to treat bipolar disorder, high blood pressure and HIV.

According to the FDA, McKesson did little to identify and quarantine other products in its distribution system that also may have been tampered with and failed to warn other pharmacies that illegitimate products were in the supply chain.

"This is simply unacceptable. A distributor’s failure to have systems in place to investigate and quarantine suspect and illegitimate products within their control is a violation of the law," said FDA commissioner Scott Gottlieb, MD, in a statement.

"But this is even more concerning given that we’re in the midst of a widespread opioid crisis. Opioids that leave the legitimate supply chain could end up being sold illegally, or a patient who was appropriately prescribed these drugs to treat pain may not get the treatment they need or may unknowingly take a medication that’s not meant for them."

The FDA did not say why it waited so long to send the warning letter or notify the public about the 2016 tampering incidents. McKesson is the first company to receive a warning letter under the Drug Supply Chain Security Act (DSCSA), which was enacted by Congress in 2013.

McKesson is one of the largest wholesale drug distributors in the country. It is being sued by dozens of states, cities and counties for its role in the opioid crisis. In 2017, McKesson was fined $150 million for failing to report suspicious orders for oxycodone, hydrocodone and other controlled substances. In 2008, the company agreed to pay $13.25 million in penalties for similar violations.

FDA: Pain Patients Dependent On Opioids Are Not Addicted

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has released new guidance to drug makers to streamline the development of buprenorphine products to treat opioid addiction. Commonly known by the brand name Suboxone, buprenorphine has long dominated the market for addiction treatment.

Of importance to pain patients is a statement about the guideline by FDA commissioner Scott Gottlieb, MD, that seeks to clarify the difference between opioid addiction and patients who need opioids for pain relief.

Gootlieb said there is still stigma and misunderstanding – even in the medical and addiction fields – about the difference between opioid addiction and dependence.

“Because of the biology of the human body, everyone who uses a meaningful dose of opioids for a modest length of time develops a physical dependence. This means that there are withdrawal symptoms after the use stops,” Gottlieb said. “A physical dependence to an opioid drug is very different than being addicted to such a medication.

“Addiction requires the continued use of opioids despite harmful consequences on someone’s life. Addiction involves a psychological preoccupation to obtain and use opioids above and beyond a physical dependence. But someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

“Someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

— Dr. Scott Gottlieb, FDA Commissioner

In recent years new and generic formulations of buprenorphine have been released in tablets, sublingual films, injections and implants, and the FDA is trying to promote the development of more of them.

The guidance released by the agency basically tells drug makers they may be able to submit new drug applications for buprenorphine products without conducting the safety and efficacy trials that are usually required for other medications.

“The guidance we’re finalizing today is one of the many steps we’re taking to help advance the development of new treatments for opioid use disorder, and promote novel formulations or delivery mechanisms of existing drugs to better tailor available medicines to individuals’ needs,” Gottlieb said. “Our goal is to advance the development of new and better ways of treating opioid use disorder to help more Americans access successful treatments.”

There are currently only three drugs approved by the FDA for medication-assisted treatment (MAT) – buprenorphine, methadone and naltrexone. Physicians wishing to prescribe buprenorphine to patients must have a special certification from the DEA and are limited in the number of patients they can treat.

Buprenorphine is an opioid that is also used to treat pain. When combined with naloxone, buprenorphine reduces cravings for opioids and lowers the risk of abuse.

Some addicts have discovered that buprenorphine can also be used to get high or to ease their withdrawal pain from heroin and other opioids. Buprenorphine is such a popular street drug that the National Forensic Laboratory Information System ranked buprenorphine as the third most diverted opioid medication in the U.S. in 2014.