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 the June 14th Wall Street Journal, Johns Hopkins University bioethicist Travis Rieder, in an excellent essay, shared with readers his battle with pain resulting from a devastating accident, the effectiveness of opioids in controlling the pain, and the hell he went through when he was too rapidly tapered off of the opioids to which he had become physically dependent. Like most patients requiring long term pain management with opioids, he developed a physical dependence, which is often mistakenly equated with addiction by policymakers and many in the media.
The aggressive schedule launched me into withdrawal, and I learned viscerally, firsthand, what the absence of opioids can do to someone whose brain has become accustomed to them. Those symptoms include increased sensitivity to the very pain that the opioids counteract, as well as extreme flu-like symptoms, insomnia and crippling depression. I came to understand why people sometimes go back onto deadly dangerous drugs: because the alternative is such profound suffering that it makes you want to die.
I have criticized policymakers for their ham-handed approach based upon a misinterpretation and misapplication of the guidelines on pain management with opioids, released in 2016 by the Centers for Disease Control and Prevention, here, here, and here. As explained in an article I co-authored in the Journal of Pain Research in February 2019, this blunt reaction is based upon the false assumption that opioid-related overdose deaths from nonmedical use is primarily a result of doctors treating patients in pain.
In his essay, Dr. Rieder levels similar criticisms:
Perhaps the greatest challenge about them [opioids] today is to resist the urge to be simplistic or reactionary. America’s current crisis of overuse has led some prescribers to avoid the drugs completely, and it has led politicians to occasionally consider ham-fisted policy solutions, like limiting the lengths or dosages of prescriptions regardless of any individual patient’s needs. But when a medication has both risks and benefits, what we need isn’t one-size-fits-all policies but nuance.
Dr. Rieder was one of dozens of scholars, academics, physicians, and pain experts who signed a letter to the Oregon Health Authority in March, authored by Stanford University Medical School Professor Sean Mackey, urging against the Authority's plans to force a rapid tapering off of opioids on all of the chronic pain patients in Oregon’s Medicaid system. That letter, plus push-back from patient advocacy groups, caused the Oregon Health Authority to put its plans on hold. It should not be lost on readers of this blog post that such interventions in the practice of medicine and the delivery of health care are part and parcel of a state-run health care system.
As I have written many times before, the opioid prescribing guidelines put forth by the Centers for Disease Control and prevention have been criticized for not being evidence-based. This has even caused the Food and Drug Administration to begin the process of developing its own set of guidelines.
In publishing the guidelines, the CDC emphasized they were meant to be suggestive, not “prescriptive,” pointing out that health care practitioners know their patients’ situations better than any regulators and should therefore individualize their prescribing to meet their patients’ unique needs.
That has not prevented the majority of states from implementing opioid prescribing guidelines that place limits on the dose, amount, and length of time that doctors can prescribe opioids—usually restricting the dose of opioids to a maximum of 90 MME (morphine milligram equivalents) per day. According to the National Conference of State Legislatures at least 30 states have implemented such guidelines. These guidelines have caused many health care practitioners to return to the undertreatment of pain for which they were criticized in the 1980s and 90s. And it has driven many chronic pain patients to desperation as their doctors abruptly taper their pain medication or cut them off entirely.
The American Medical Association has gently criticized the misinterpretation and misapplication of the CDC guidelines in the past. Now two and a half years after the CDC published its guidelines, the AMA has taken a more adamant stand. This week, at the AMA’s interim meeting in Maryland, its House of Delegates resolved:
RESOLVED that our AMA affirms that some patients with acute or chronic pain can benefit from taking opioids at greater dosages than recommended by the CDC Guidelines for Prescribing Opioids for chronic pain and that such care may be medically necessary and appropriate.
RESOLVED that our AMA advocate against the misapplication of the CDC Guidelines for Prescribing Opioids by pharmacists, health insurers, pharmacy benefit managers, legislatures, and governmental and private regulatory bodies in ways that prevent or limit access to opioid analgesia.
RESOLVED that our AMA advocate that no entity should use MME thresholds as anything more than guidance, and physicians should not be subject to professional discipline, loss of board certification, loss of clinical privileges, criminal prosecution, civil liability, or other penalties or practice limitations solely for prescribing opioids at a quantitative level above the MME thresholds found in the CDC Guidelines for Prescribing Opioids.
Sadly, the opiophobia-driven policy train left the station long ago. As an eternal optimist, my initial reaction is to think, “better late than never,” and to hope this new resolution will cause policymakers to reconsider their misguided policy. But the cynical voice inside me responds with a more negative cliché: “a day late and a dollar short.”
On November 2 the Food and Drug Administration announced the approval of Dsuvia, a sublingual tablet containing the powerful fentanyl analog, sufentanil. Sufentanil has been used for years in the hospital setting, primarily in intravenous form for anesthesia. It is roughly 5 to 10 times more potent than fentanyl, and thus has a significant overdose potential. The FDA reached this decision following a 10-3 vote in favor of the drug’s approval by the Anesthetic and Analgesia Drug Products Advisory Committee (AADPAC), based on data from multicenter trials. It was not approved for outpatient use, but for use only in medically supervised settings, and may be of particular benefit to military health care practitioners.
FDA Commissioner Gottlieb’s announcement stated:
Dsuvia, which was previously approved by the European Medicines Agency in July under the brand name Dzuveo, has some unique features in that the drug is delivered in a stable form that makes it ideally suited for certain special circumstances where patients may not be able to swallow oral medication, and where access to intravenous pain relief is not possible. This includes potential uses on the battlefield. For this reason, the Department of Defense (DoD) worked closely with the sponsor on the development of this new medicine. This opioid formulation, along with Dsuvia’s unique delivery device, was a priority medical product for the Pentagon because it fills a specific and important, but limited, unmet medical need in treating our nation’s soldiers on the battlefield. The involvement and needs of the DoD in treating soldiers on the battlefield were discussed by the advisory committee.
The announcement was met with criticism from numerous quarters, including Anesthesiology Professor Raeford Brown of the University of Kentucky, who chairs the AADPAC, Senator Edward Markey (D-MA), and the advocacy group Public Citizen. They questioned the need for the development of a new and potent opioid in the presence of the opioid overdose crisis, and raised concerns about the potential for the drug’s diversion to the black market for non-medical users. These objections were trumpeted by the media.
The concerns raised by critics are unfounded. According to the Drug Enforcement Administration, most fentanyl and fentanyl analogs found on the streets are in an illicit powdered form, made in labs overseas and smuggled into the US via the mail, Fedex, and UPS, or using Mexican drug cartel infrastructure. While much of it is mixed in with heroin or cocaine, many dealers own pill presses and press the powder into counterfeit oxycodone or hydrocodone pills that are sold to unsuspecting nonmedical users. That’s how the artist known as Prince died. He liked to use Vicodin (hydrocodone) recreationally. Records show he never obtained any prescriptions from doctors. His dealer sold him what was believed to be Vicodin but was actually counterfeit and made from fentanyl, which caused his overdose death.
Recrudescent opiophobia now evokes positions held at the zenith of President Nixon’s war on drugs. The fact remains that opioids can be highly effective in treating pain, especially in the acute setting. Hysteria-driven policy should not stifle innovations in this or other forms of pain management.
Commissioner Gottlieb also stated in the FDA announcement:
We owe an answer to patients with medical pain, and the innovators who take risks to develop products to help address their needs. We owe it to Americans who want the FDA to do our part to help end one of the biggest addiction crises of modern times, while we carefully balance these grave risks against patient needs.
Commissioner Gottlieb made the right call here.
Late last week UPI news ran a report by E.J. Mundell with the headline, “Government efforts to curb opioid prescriptions might have backfired.” It cites two separate studies published online in JAMA Surgery on August 22 that examined two different restrictive opioid policies that fell victim to the Law of Unintended Consequences.
The first study, by researchers at the University of Michigan, evaluated the impact of the Drug Enforcement Administration’s 2014 rescheduling of hydrocodone (Vicodin) from Schedule III to Schedule II. Prescriptions for Schedule III narcotics may be phoned or faxed in by providers, but Schedule II narcotics require the patient to see the prescriber in person in order to obtain a prescription. The DEA’s goal was to reduce the number of Vicodin pills, popular with non-medical users, available for diversion to the black market.
The study looked at 21,955 post-surgical patients across 75 hospitals in Michigan between 2012 and 2015 and found that the number of hydrocodone pills prescribed after the 2014 schedule change increased by an average of seven 5mg tablets. The total Oral Morphine Equivalent of prescribed hydrocodone did not change significantly after the DEA made hydrocodone Schedule II. However, the refill rate decreased after the change. The study’s abstract concluded, “Changing hydrocodone from schedule III to schedule II was associated with an increase in the amount of opioids filled in the initial prescription following surgery.”
As a practicing general surgeon, my initial reaction to this study was: “Tell me something I don’t know.” Prior to the 2014 schedule change, I would often start off prescribing a small amount of hydrocodone to some of my post-op patients (depending upon the procedure and the patient’s medical history) with the knowledge that I can phone in a refill for those patients who were still in need of it for their pain after the initial supply ran out. Once it was rescheduled, I changed my prescribing habits. Not wanting any of my patients to run out after hours, over a weekend, or on a holiday—when the office is closed and their only recourse would be to go to an emergency room or urgent care center to get a prescription refill—I increased the amount I prescribe (based on my best estimate of the maximum amount of days any individual patient might need hydrocodone) to reduce the chances of them needing a refill. This results in some patients having leftover Vicodin pills in their medicine cabinet. On the other hand, fewer of those patients need refills.
Not surprisingly, many of my clinical peers have done the same thing. It’s not a surprise because most physicians place the interests of their patients ahead of the interests of regulators and bureaucrats. So the adjustment made in postoperative hydrocodone prescribing was basically a “no brainer.”
On August 22, Food and Drug Commissioner Scott Gottlieb issued a press release announcing the FDA plans to contract with the National Academies of Sciences, Engineering, and Medicine (NASEM) to develop evidence-based guidelines for the appropriate prescribing of opioids for acute and post-surgical pain. The press release stated:
The primary scope of this work is to understand what evidence is needed to ensure that all current and future clinical practice guidelines for opioid analgesic prescribing are sufficient, and what research is needed to generate that evidence in a practical and feasible manner.
The FDA will ask NASEM to consult a “broad range of stakeholders” to contribute expert knowledge and opinions regarding existing guidelines and point out emerging evidence and public policy concerns related to the prescribing of opioids, utilizing the expertise within the various medical specialties.
Recognizing the work of the Centers for Disease Control and Prevention for having “taken an initial step in developing federal guidelines,” Commissioner Gottlieb diplomatically stated the FDA initiative intends to “build on that work by generating evidence-based guidelines where needed” that would differ from the CDC’s endeavor because it would be “indication-specific” and based on “prospectively gathered evidence drawn from evaluations of clinical practice and the treatment of pain.”
The CDC guidelines for prescribing opioids, released in early 2016 and updated in 2017, have been criticized by addiction and pain medicine specialists for not being evidence-based. Unfortunately, these guidelines have been used as the basis for many new prescribing regulations instituted at the state-level and proposed on the federal level. The American Medical Association and other medical specialty organizations have spoken out against proposed federal prescription limits that are based upon an inaccurate interpretation of the flawed CDC guidelines.
In May, Commissioner Gottlieb, in a blog post, mentioned he was aware of criticisms as well as complaints by patient and patient-advocacy groups and was interested in developing more “evidence-based information” on the matter of opioids and pain management.
Now it appears he is taking the next step. While the press release language was diplomatic and avoided any notion of disrespect for the CDC’s efforts, it is difficult not to infer that the Commissioner agrees with many who have been criticizing the CDC guidelines over the past couple of years.