On August 26 Oklahoma State Judge Thad Balkman ruled that Johnson & Johnson must pay $572 million to the state of Oklahoma for contributing to the local opioid addiction crisis. Johnson & Johnson sold two opioids: a fentanyl skin patch with the brand name Duragesic, and Nucynta,a synthetic opioid similar to tramadol but stronger.
Nucynta is not as addictive as most other synthetic and semi-synthetic opioids and has been shown to have low levels of abuse in post-marketing studies. Fentanyl skin patches are very difficult and inconvenient to convert for non-medical use. The Drug Enforcement Administration claims that nearly all the fentanyl seized is so-called "illicit fentanyl," manufactured mostly in powdered form in clandestine labs in Asia and Mexico, and then smuggled in to the U.S., sometimes via the Postal Service.
Johnson & Johnson was also charged with contributing to the overdose crisis because it owns two subsidiaries that make the active ingredients and narcotic raw materials used by other opioid manufacturers.
Two other opioid manufacturers, Purdue Pharma and Teva Pharmaceuticals, settled with the state, but Johnson & Johnson decided to take the case to trial. Their attorneys say the company plans to appeal the decision.
This is nothing more than a shakedown. As I have written here and here, the government’s own data show no correlation between prescription volume and the non-medical use of opioids or opioid use disorder. In fact, as prescription volume has come down, overdoses have gone up. That’s because as it has become more difficult and expensive to divert prescription pain pills to the underground market for non-medical use, non-medical users have migrated to heroin and fentanyl that the efficient black market is supplying in abundance.
Policymakers and politicians refuse to accept the fact that it is the current policy—drug prohibition—that is the cause of the opioid overdose crisis. Rather than taking a hard look at the dismal failure of America’s longest war, the war on drugs, they just double down on what clearly isn’t working, and seek scapegoats for the death and destruction the war continues to bring.
Oklahoma has extracted some tribute from Purdue Pharma and Teva Pharmaceuticals and, pending appeal, hopes to extract even more from Johnson & Johnson. If enough jurisdictions are successful in getting their piece of the action, we might see drug makers pull out of the pain reliever business altogether. That will not be good for millions of pain sufferers.
While state and municipal coffers may get some quick cash infusions, and some political careers may get a needed boost, this shakedown will not get one IV drug user to pull the needle out of their arm.
A letter to the editor in the August 14 New England Journal of Medicine by researchers at the University of Michigan proudly reported on the results of their effort, called the Michigan Surgical Quality Collaborative (MSQC), to reduce the volume of opioids prescribed for postoperative pain. The Collaborative developed a set of guidelines for its participating prescribers.
As a result, they found that from January 2017 through May 2018, the mean number of pills prescribed for postoperative pain decreased from 26 (+/-2) pills pre-guideline to 18 (+/– 3) pills post-guideline. Patient pill consumption also decreased from an average of 12 pills (+/-1) pre-guideline to 9 pills (+/-2) post-guideline. During that period there was no discernible difference in the pain scores reported by these patients pre-and post-guideline.
It seems all of health care is now fixated on getting the number of prescription pain pills down. Yet there is no correlation between prescription volume and nonmedical use or use disorder/addiction. And as prescription volume has dramatically come down since 2010, the overdose rate has dramatically increased. Furthermore, in 2017 at least 75% of opioid-related overdoses were from heroin or fentanyl, while 40% of overdoses involving prescription opioids had multiple other drugs onboard, including heroin, fentanyl, alcohol, and tranquilizers.
So, as academic physicians continue to virtue signal and show the media and regulators how well they are complying with the "new opiophobia" by reducing opioid prescribing, the overdose rate continues to climb.
To be fair, an oversupply of prescription pain pills to patients can lead to more pills getting diverted into the black market for nonmedical users. But as a doctor who cares about reducing deaths, I would prefer that nonmedical users take diverted prescription opioids as opposed to heroin or fentanyl or counterfeit prescription pills made from fentanyl.
The focus should be on the number of deaths, not the number of pills. For that to happen, policy must to shift to harm reduction.
It seems that no amount of data-driven information can get policymakers to reconsider the hysteria-driven pain prescription policies they continue to put in place.
I can understand lay politicians and members of the press misconstruing addiction and dependency, but there is no excuse when doctors make that error. Yet National Public Radio reports that surgeons in 18 Upstate New York hospitals have agreed on an initiative to limit the amount of pain medicine they will prescribe to postoperative patients discharged from the hospital. The reporter says that researchers “now know” that patients prescribed opioids for postoperative pain “can become addicted” and that “the new prescription guidelines can prevent this particular gateway to abuse.”
But what does the research show? One recent study published in the BMJ of more than 568,000 “opioid naïve” postsurgical patients followed for 8 years found a total “misuse” rate of 0.6 percent. (“Misuse” includes a range of non-prescribed drug use, from self-medicating with leftover pills to treat an ankle sprain on one extreme to addiction on the other.) Broken down further, the researchers found the misuse rate was 0.15 percent in patients given just one prescription postoperatively and was 0.29 percent in patients who got a second prescription as a refill.
Multiple highly-respected Cochrane systematic analyses, the most rigorous reviews in the medical science literature, found the addiction rate in chronic noncancer pain patients on long-term opioid therapy to be around 1 percent.
Addiction and dependency/tolerance are two separate entities, but policymakers and many in the media equate the two. But the doctors in Upstate New York should know better. Physical dependence refers to the physiological adaptation to the drug such that abrupt cessation or tapering off too rapidly can precipitate a withdrawal syndrome, which in some cases can be life-threatening. Tolerance is an aspect of physiological adaptation, in which increasing dose of a medication become necessary to achieve the desired effect. Once a patient is properly tapered off of the drug on which they have become physically dependent, they do not feel a craving or compulsion to return to the drug. Dependence and tolerance are seen with numerous types of drugs, from anti-depressants and anti-epileptics to beta-blockers (used to treat hypertension and other cardiovascular conditions).
Addiction, on the other hand, is defined by the American Society of Addiction Medicine as a “chronic disease of brain reward, motivation, memory and related circuitry…characterized by the inability to consistently abstain, impairment in behavioral control, craving” that continues despite resulting destruction of relationships, economic conditions, and health. Addiction has a biopsychosocial basis with a genetic predisposition and involves neurotransmitters and interactions within reward centers of the brain. Some experts believe addiction is a learning disorder in which behavioral patterns are automatized as mechanisms for coping with stress or trauma. A major feature of addiction is compulsiveness. This compulsiveness is why alcoholics or other drug addicts will return to their substance of abuse even after they have been “detoxed” and despite the fact that they know it will further damage their lives.
Writing in the New England Journal of Medicine in 2016, Drs. Nora Volkow and Thomas McLellan of the National Institute on Drug Abuse explained, “Unlike tolerance and physical dependence, addiction is not a predictable result of opioid prescribing. Addiction occurs in only a small percentage of persons who are exposed to opioids — even among those with preexisting vulnerabilities.”
In 2016 the Centers for Disease Control and Prevention published guidelines regarding opioid prescribing for pain. Many scholars and clinicians specializing in pain management and addiction treatment criticized the guide as lacking a basis in evidence. Despite the fact that the CDC stated its guidelines were meant to be “voluntary rather than prescriptive standards, “ and that much of the guidelines were based on “Type 4 evidence” (defined as “based upon clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations”), policymakers on the federal and state level have been quick to adopt many of these guidelines as statutory limitations on opioid prescribing. The guidelines recognized that “clinical decision making should be based on a relationship between the clinician and patient, and an understanding of the patient’s clinical situation, functioning, and life context.” But one-size-fits all limitations on prescription dosages and amounts implemented by policymakers are incompatible with that statement.
An outcry from chronic pain patients experiencing the rapid tapering or termination of their chronic opioid treatment that followed in the wake of statutory enactments of the CDC guidelines led former Food and Drug Administration Commissioner Scott Gottlieb to order a meeting on “Patient-Focused Drug Development for Chronic Pain” on July 9, 2018, stating in the meeting announcement: “In short, having sound, evidence-based information to inform prescribing can help ensure that patients aren’t over prescribed these drugs; while at the same time also making sure that patients with appropriated needs for short and, in some cases, longer-term use of these medicines are not denied access to necessary treatments. We will take the first steps toward developing this framework in the coming months, with the goal of providing standards that could inform the development of evidence based guidelines (emphasis added).” Thus, the Commissioner implied his sympathy with criticisms raised by academic and clinical physicians and their patients regarding the misinterpretation and misapplication of guidelines that lacked a solid basis on the evidence.
Complaints by academicians, clinicians, and the American Medical Association(Resolution 235) finally caused the CDC to issue a clarification in April 2019, noting, “Some policies, practices attributed to the Guideline are inconsistent with its recommendations.” Among the misapplications of the guidelines it noted were those that result in “hard limits or ‘cutting off’ opioids,” stating the “Guideline does not support abrupt tapering or sudden discontinuation of opioids.”
Yet the statutory and regulatory restrictions remain unchanged. To date 18 states have laws limiting the amount of opioids that can be prescribed for acute and chronic pain. Many have limits on the morphine milligram equivalent daily dose (MEDD) that may be prescribed, despite evidence in the peer-review science literature that MEDD is an inaccurate and inappropriate metric. And it appears that even many actively practicing physicians, such as the surgeons in the 18 upstate New York hospitals, ignore the science as well as pleas from patients.
So the march continues, undeterred by the facts, toward a pre-modern approach to the understanding and treatment of pain, and a pre-modern understanding of the risks and benefits of opioids, and the subtleties that differentiate dependency from addiction.
In February of this year, I co-authored a paper in the Journal of Pain Research explaining why there is no correlation between the amount of opioids prescribed and the incidence of non-medical use or prescription pain-reliever use disorder. That same month my colleague Jeffrey Miron and co-authors revealed similar findings in this Cato Institute Policy Analysis.
Now researchers in Germany have provided more evidence to pour cold water on the idea of any relationship between the volume of opioid prescribing and the incidence of opioid use disorder. Publishing in the German Medical Association’s international science journal, they found that “the number of persons addicted to opioids in Germany has hardly changed over the past 20 years,” with an average of 3.1 persons per 1000 inhabitants across Germany. This compares to data from the U.S. National Survey on Drug Use And Health showing no significant change in “pain reliever use disorder” in persons aged 12 and above from 2002-2014.
Germany ranks second only to the U.S. in opioid prescription volume. Canada and Australia rank third and sixth respectively. An international group of investigators recently compared the opioid prescription volume per capita of Canada, Australia, Germany, and the U.S., from 1980-2015 using data provided by the International Narcotics Control Board and the World Health Organization. In the U.S., opioid volume (measured as morphine milligram equivalents per capita) began to increase in the late 1980s, accelerated in the mid-90s, and then surged in the early part of this century, peaked in 2012 and then began to taper. In Germany the increase in prescribing began slightly later than in the U.S.—in the mid-90s. But, as in the U.S., it surged in the early 2000s, peaked in 2012, and then began to recede. (The prescribing patterns followed similar trend lines in Australia and Canada but had not shown any evidence of peaking by 2015.)
A big takeaway is that, just as there is no correlation between prescription volume and opioid use disorder in the U.S., so too there is no correlation between prescription volume and addiction in Germany. But another point of comparison must not go unnoticed: the U.S. leads the developed world in per capita opioid-related overdose deaths, while Germany's overdose rate is among the lowest in the developed world.
Germany’s overdose rate has been essentially unchanged for most of this century. Opioids were considered responsible for just under 800 overdose deaths in 2016, compared to more than 42,000 deaths in the U.S. that year. Also unlike the U.S., Germany has embraced harm reduction strategies for the treatment of substance use disorder and non-medical drug use for decades. These strategies include Safe Injection Facilities, needle exchange programs, Medication Assisted Treatment and Heroin Assisted Treatment, and distribution of test strips and naloxone.
U.S. and state policymakers remain obsessed over curtailing the prescription of opioids to patients in pain while the overdose rate continues to climb and patients suffer needlessly. To reduce overdoses, U.S. policy must shift from a war on drugs to a war on drug-related deaths. This means following Germany's example and making harm reduction the central goal.
With clear evidence that restricting the number of prescriptions increased the death rate by driving non-medical users to heroin and fentanyl, the last thing one wants to hear about is a politician planning to double down on this deadly policy by calling for further prescription limits for patients in pain.
Yet Senator Robert Portman (R-OH) is proposing legislation that would impose a national 3-day limit on opioid prescriptions following surgeries. He will be kind enough to allow exceptions for people dealing with cancer, chronic pain, and “other serious matters”—whatever that means.
Government data show there is no correlation between the number of opioids prescribed and their non-medical use or the development of opioid use disorder. Overdose rates skyrocketed during the last 10 years while high-dose opioid prescriptions dropped more than 58 percent and total volume of dispensed opioids dropped more than 29 percent. Seventy-five percent of opioid-related deaths in 2017 involved fentanyl and heroin, and fewer than 10 percent involved prescription pain pills without also involving heroin, fentanyl, cocaine, tranquilizers, or alcohol.
The senator has determined that, “After the second or third [postoperative] day, other pain medications work just as effective (sic)." In my more than 35 years as a practicing general surgeon, I usually find that my patients recovering from major surgery require prescription opioids to control their pain for more than 2 or 3 days. It is bad enough that many states have imposed 5 or 7 day limits on opioid prescriptions, forcing many patients in severe pain to make multiple trips to the doctors office for refills. Imposing a national 3-day limit lacks an understanding of the science. It would be an unfounded and callous government intrusion into the practice of medicine.
Senator Portman, like so many other politicians untrained in medicine or pharmacology, is guilty of misinterpreting and misapplying the guidelines on opioid prescribing published in 2016 by the Centers for Disease Control and Prevention. He must still believe that today’s non-medical users are yesterday’s pain patients, even though, as mentioned above, there is no evidence of any correlation between the two.
He also seems to think there is a high risk of addiction in patients prescribed opioids for acute post-surgical pain. Yet a well-publicized study in the medical journal BMJ by researchers at Harvard and Johns Hopkins looked at 568,000 opioid “naïve” patients in the Aetna health insurance data base given prescription opioids for acute postoperative pain over the period of 2008-2016. The researchers found the “total misuse rate,” i.e., rate of all opioid misuse diagnoses among the 568,000 patients prescribed the opioids, was 0.6 percent.
Senator Portman told Ohio reporters, “After day four, five or six, the chances of becoming addicted are higher.” Maybe he is reacting to the statement by the researchers in the BMJ report that each refill and additional week of opioid use was “associated with an adjusted increase in the rate of misuse of 44%.” But a deeper look at their data shows the incidence of opioid misuse rose from 145 cases per 100,000 person years, or 0.15 percent per year, in patients who had no refills, to 293 cases per 100,000 person years, or 0.29 percent per year, for persons who had one refill. Indeed, that is nearly double. But if you nearly double a very low number, you still get a low number.
The fact is the overdose rate from the non-medical use of licit and illicit drugs has been on a steady exponential increase since the 1970s and shows no signs of slowing down. The only thing that has changed over the years is the particular drug in popular use at any given time. The reasons behind this are complex and multifactorial, and likely sociocultural and psychosocial. In the early part of this century the popular drugs for non-medical users were diverted prescription opioids. Next it became heroin. For the past several years it has been heroin and fentanyl. Methamphetamine related deaths are now surging to all-time high levels, and preliminary estimates from the CDC place the number of meth-related deaths at nearly 13,000 in 2018—eclipsing the number for prescription opioid-involved deaths.
Senator Portman is two or three drugs behind in his prosecution of the drug war.
To bring the death rate down, Senator Portman should learn a lesson from his home state of Ohio, where a recent embrace of harm reduction measures—expanding needle exchange programs, distributing the overdose antidote naloxone, and increasing access to Medication Assisted Treatment—has led to a 23.3 percent drop in overdose deaths in 2018 according preliminary CDC data. Harm reduction is a proven strategy for saving lives.
If Senator Portman wishes to craft legislation that can truly save lives, he should propose a repeal of the federal “Crack House Statute.” This law stands in the way of many of the country’s largest cities that wish to establish Safe Injection Facilities, which are preventing overdoses and saving lives in more than 120 cities throughout Europe, Canada, and Australia.
The Washington Post recently received access to a database maintained by the Drug Enforcement Administration that tracks the manufacture and distribution of every prescription opioid in the country. It reported that 76 billion pills were distributed throughout the US between 2006 and 2012, with higher volumes shipped to the areas that were most hard hit with opioid-related overdose deaths.
This is being offered as proof that the overprescribing of prescription opioids caused the overdose crisis. But this flies in the face of other powerful evidence. Research reported in the Journal of Pain Research last February that examined data from the National Survey on Drug Use and Health as well as the Centers for Disease Control and Prevention show there is no correlation between the number of pain pill prescriptions and “past-month nonmedical use” or past-year diagnosis of “pain reliever use disorder” among adults. This was corroborated by a study published by the Cato Institute the same month.
Research from the University of Pittsburgh shows overdose deaths from nonmedical use of licit and illicit drugs have been on a steady exponential increase since the 1970s, with no evidence of slowing. The only changes over the decades pertain to the particular drug in vogue during any period. In the early part of this century, the drugs in vogue were diverted prescription opioids.
To be sure, the lure of easy money offered by a black market fueled by drug prohibition brings out the worst in people, and doctors and pharmacists were no exception. Some doctors and pharmacists leveraged their professional licenses and teamed up with regional drug dealers to supply nonmedical users with large quantities of their preferred drug. But the blame for such behavior should be placed where it belongs: drug prohibition.
Those unethical health care providers were the exception, not the rule. And they were providing drugs to mostly nonmedical users, sometimes under the guise of providing patient care. Meanwhile, the nonmedical use of prescription opioids peaked in 2012, as heroin became cheaper and more available than diverted pain pills. The prescription of high-dose opioids peaked in 2008 and the number dropped more than 58 percent by 2017. Yet the overdose rate accelerated as the prescription numbers decreased, because nonmedical users migrated to more readily available heroin and fentanyl. By 2015 there was already evidence that heroin was becoming the new drug in vogue, as up to one-third of heroin addicts undergoing rehab stated they initiated drug use with the opioid heroin.
The CDC released preliminary estimates of 2018 opioid-related overdose deaths July 17, and they suggest the death toll may be tapering off slightly, down to 47,590 from roughly 49,000 in 2017. One aspect of these numbers the media failed to report was that 67 percent of those deaths involved illicit fentanyl, one-third involved heroin, and just under one-third also involved cocaine. About one-fourth of opioid-related overdose deaths involved any prescription pain killer, and more than three quarters of them also involved heroin, fentanyl, cocaine, or tranquilizers.
The overdose problem has never been a product of doctors treating patients for pain. It has always been a product of (a growing population of) nonmedical users accessing drugs in a dangerous black market fueled by drug prohibition. While the possible downturn or leveling off in the mortality rate is encouraging, this can largely be attributed to the adoption of harm reduction measures, such as naloxone distribution and needle-exchange programs, which need to be more widely-adopted.
The number of opioids prescribed greatly increased during the early part of this century, as doctors were--rightly--encouraged to be more concerned with alleviating pain and patients were--rightly--assured that opioids in the medical setting have a low overdose and addiction potential. That meant more pain pills were available for diversion to the black market for nonmedical use. And, as mentioned above, there were some doctors and pharmacists who were unethical and unscrupulous. But, at the end of the day, there is no correlation between the number of pills prescribed and the incidence of nonmedical use or use disorder.
The continued obsession about the number of pain pills being prescribed causes patients to go undertreated for their pain and will not make one IV drug user pull the needle out of their arm.
Senator Joe Manchin (D-WV) and Mike Braun (R-IN) are still trying to address the fentanyl and heroin overdose crisis—soon to be joined by a methamphetamine and cocaine overdose crisis—by denying chronic pain patients access to pain relief. They have just introduced a bill they call The FDA Opioid Labeling Accuracy Act, which would “prohibit the Food and Drug Administration (FDA) from allowing opioids to be labeled for intended use of ‘around-the-clock, long-term opioid treatment’ until a study can be completed on the long-term use of opioids.”
Set aside the fact that most pain specialists agree that, in some cases, long-term opioid therapy is all that works for some chronic pain patients. The 2016 guidelines on opioid prescribing put forth by the Centers for Disease Control and Prevention have already been misinterpreted and misapplied by legislators and regulators, leading to forced and rapid tapering off of opioids in many chronic pain patients, causing many to resume lives immobilized by pain, and in many cases, seek relief in the black market or by suicide. It has gotten so bad that the CDC recently issued a “clarification” in April, reminding regulators that the guidelines were only meant to be suggestive, not prescriptive, and did not in any way mean to encourage the rapid tapering of patients on chronic opioids for pain management. Johns Hopkins bioethicist Travis Rieder, PhD delves deeply into this subject and relates his own experiences in his book, In Pain.
What the senators fail to recognize is that patients are not one-size-fits-all. Different patients respond to pain and to pain management differently. Their proposed legislation, if passed, will only serve to exacerbate the unnecessary suffering of patients in pain that the CDC is trying to undue with its guideline clarification.
Meanwhile, they should take a look at the government’s own numbers. The data show there is no correlation between the number of prescriptions written and the incidence of non-medical use of prescription opioids or prescription pain reliever use disorder. And less than 10 percent of opioid-related overdose deaths in 2017 involved prescription pain relievers unaccompanied by other drugs such as cocaine, heroin, alcohol, or fentanyl.
The continued war on patients by politicians and regulators will not get one IV heroin user to take the needle out of their arm. Senators Manchin and Braun need to recognize that the overdose crisis has been on a steady, exponential increase since the 1970s and shows no signs of stopping—and that its ultimate cause is drug prohibition.
If they want to get serious about addressing the problem, they should switch their focus to harm reduction. A good way to start would be to repeal the “Crack House” statutes that prevent cities and states from establishing overdose prevention sites called “safe injection facilities.”