Opioid Prescriptions Plunge to 15-Year Low

By Pat Anson, Editor

The volume of opioid prescriptions in the United States has fallen sharply and now stand at their lowest levels since 2003, according to data released by the Food and Drug Administration.

Over 74 million metric tons of opioid analgesics were dispensed in the first six months of 2018, down more than 16 percent from the first half of 2017. Opioid prescriptions have been declining for several years, but the trend appears to be accelerating as many doctors lower doses, write fewer prescriptions or simply discharge pain patients.

“These trends seem to suggest that the policy efforts that we’ve taken are working as providers, payers and patients are collectively reducing some of their use of prescription opioid analgesic drugs,” said FDA commissioner Scott Gottlieb, MD, in a statement.

SOURCE: FDA AND IQVIA

"This graph confirms the perception that many of use have, that prescribing continues to decline," said Bob Twillman, PhD, Executive Director of Academy of Integrative Pain Management. "But, the question remains --what is the effect of this decreased prescribing on people with chronic pain?

"Measures of prescribing need to be matched with measures of patient function and quality of life, especially given evidence that decreased prescribing may actually be associated with increased suicide. All this measure really tells us is that the intense pressure from legislators, regulators, and payers has had its desired effect of driving down prescribing, even it there’s no evidence that it’s done anything else helpful."

While opioid prescriptions decline, overdoses continue to rise. According to preliminary data from the CDC, nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl and heroin, not prescription opioids.

“It isn’t necessarily the case that more people are suddenly switching from prescription opioids to these illicit drugs. The idea of people switching to illicit drugs isn’t new as an addiction expands, and some people have a harder time maintaining a supply of prescription drugs from doctors,” said Gottlieb. “What’s new is that more people are now switching to highly potent drugs that are far deadlier. That’s driven largely by the growing availability of the illicit fentanyls.”

Illicit fentanyl and its chemical cousins are synthetic opioids, 50 to 100 times more potent than morphine. They are produced largely by clandestine drug labs in China and then smuggled into the U.S., where they are often mixed with heroin, cocaine and counterfeit drugs.  A record 1,640 pounds of fentanyl and nearly 5,500 pounds of heroin have been seized by law enforcement so far this year; likely a small fraction of what’s available on the black market.

While the Trump administration has expanded efforts to stop the distribution and sale of illicit opioids, it also remains focused on reducing the supply of prescription opioids.  The FDA plans to develop new prescribing guidelines for treating short-term, acute pain that will likely set a cap on the number of pills that can be prescribed for certain medical conditions.

“No more 30-day prescriptions for a tooth extraction or an appendectomy,” said Gottlieb.

The Justice Department also recently announced plans to lower production quotas by 10% next year for six widely prescribed opioid medications. The goal of the administration is to reduce opioid prescriptions by a third in the next three years. 

“The number of opioid prescriptions is only one of many factors and may not be the most important factor contributing to the opioid crisis. In fact, the U.S. is at a 15-year low in the amount of opioid prescribed but continues to see a surge of drug overdoses,” said Lynn Webster, MD, a pain management expert and past president of the American Academy of Pain Medicine.

“Much of the effort to curb the amount of prescription opioids has contributed to more suffering by people in chronic pain and possibly the increase in suicides.  It also hasn't done anything to curb the number of overdose deaths. Rather than being focused on number of pills or amount of opioid prescribed we need to focus on what is the best and most appropriate treatment for individual patients. When that is done properly, the right amount of opioids will be prescribed.”  

90% of Massachusetts Overdoses Linked to Fentanyl

By Pat Anson, Editor

Nearly 90 percent of opioid-related overdose deaths in Massachusetts now involve fentanyl, according to a new report that documents the rapidly changing nature of the opioid crisis. Less than 20 percent of drug overdoses in the state were linked to prescription opioids.

In the second quarter of 2018, Massachusetts health officials say 498 people died from an opioid-related overdose – the third straight quarter that opioid deaths have declined.

But the good news was tempered by the rising toll taken by fentanyl -- the synthetic opioid that’s become a deadly scourge on the black market. Fentanyl is often mixed with heroin, cocaine and counterfeit drugs to increase their potency. 

Because Massachusetts was one of the first states to conduct blood toxicology tests in overdose cases, it’s quarterly reports on drug deaths are considered more accurate than federal estimates and more likely to spot emerging trends in drug use. 

"This quarterly report provides a new level of data revealing an unsettling correlation between high levels of synthetic fentanyl present in toxicology reports and overdose death rates. It is critically important that the Commonwealth understand and study this information so we can better respond to this disease and help more people,” Massachusetts Gov. Charlie Baker said in a statement.

Another trend documented in Massachusetts is the increasing role played by cocaine and benzodiazepines --- an anti-anxiety medication – in drug overdoses. In the first quarter of 2018, cocaine (43%) and benzodiazepines (42%) were involved in more overdoses than heroin (34%) and prescription opioids (19%). 

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

Drug experts say many cocaine users may not realize their drug has been spiked with fentanyl, while many people who buy Xanax or Valium on the black market don’t know they’re getting counterfeit medication laced with fentanyl.

“If you are using illicit drugs in Massachusetts, you really have to be aware that fentanyl is a risk no matter which drug you’re using,” Dr. Monica Bharel, Massachusetts public health commissioner told The Boston Globe. “The increased risk of death related to fentanyl is what’s driving this epidemic.”

Fentanyl is also involved in a growing number of fatal overdoses in Pennsylvania. According to the Drug Enforcement Administration, there were 5,456 overdose deaths in Pennsylvania last year. Of those, over 67% percent involved fentanyl. The presence of fentanyl or its chemical cousins in overdose deaths rose almost 400% in the state from 2015 to 2017.

Most overdoses involve multiple drugs and blood tests alone do not determine a cause of death -- only which drugs were present at the time of death.

Former CDC Director Arrested for Sexual Misconduct

By Pat Anson, Editor

Dr. Thomas Frieden, the former director of the Centers for Disease Control of Prevention, has been arrested on sexual misconduct charges in New York City.

Frieden turned himself in to police in Brooklyn Friday morning after being charged with forcible touching, harassment and third degree sex abuse, all misdemeanors. The charges stem from a complaint filed in July by a 55-year old unnamed woman who alleges the 57-year old doctor grabbed her buttocks without permission in his apartment last October. 

According to STAT, Frieden later apologized to the woman -- a longtime family friend -- and "tried to manipulate her into staying silent by citing his position and potential to save lives around the world."

Fried was arraigned Friday afternoon and released without bail, after a judge ordered him not to contact his accuser and to surrender his passport. He's due back in court October 11.

Frieden did not enter a plea. A spokesperson released a statement saying the incident "does not reflect Dr. Frieden’s public or private behavior or his values over a lifetime of service to improve health around the world.”

Frieden led the CDC from 2009 to 2017 and championed the agency’s controversial opioid prescribing guideline -- calling it an "excellent starting point" to prevent opioid abuse.

Although voluntary and only intended for primary care physicians, the guideline has been widely adopted by insurers, states and healthcare providers – resulting in many chronic pain patients losing access to opioid medication.

“This crisis was caused, in large part, by decades of prescribing too many opioids for too many conditions where they provide minimal benefit," Frieden wrote in a commentary published by Fox News.  “There are safer drugs and treatment approaches that can control pain as well or better than opioids for the vast majority of patients."

DR. THOMAS FRIEDEN

Frieden currently heads Resolve to Save Lives, a program of Vital Strategies, a non-profit health organization that is trying to improve public health worldwide.

Vital Strategies released a statement saying Frieden informed the organization in April about the misconduct allegation. His accuser does not work for Vital Strategies, but the organization hired an investigator to interview employees about Frieden. No inappropriate workplace behavior or harassment was found, according to Vital Strategies CEO Jose Castro.  

“I have known and worked closely with Dr. Frieden for nearly 30 years and have seen first-hand that he has the highest ethical standards both personally and professionally. Vital Strategies greatly values the work Dr. Frieden does to advance public health and he has my full confidence,” said Castro.

Frieden has an extensive background in epidemiology and infectious diseases, and his tenure at the CDC was marked by major efforts to combat the Ebola virus, fungal meningitis, influenza and the Zika virus.

Before his appointment as CDC director, Frieden was New York City’s health commissioner, where he led efforts to ban public smoking and remove unhealthy trans fats from restaurants. Frieden is married and has two children.

FDA to Develop Acute Pain Guidelines

By Pat Anson, Editor

The head of the U.S. Food and Drug Administration is following up on a promise to develop new federal prescribing guidelines for treating short-term, acute pain. But don't expect an overhaul of the CDC's controversial opioid guideline.

FDA commissioner Scott Gottlieb, MD, announced today that his agency has awarded a contract  to the National Academies of Sciences, Engineering, and Medicine (NASEM) to help develop guidelines for prescribing opioids for acute pain that results from specific medical conditions or procedures, such as wisdom tooth removal or post-operative pain.  

The CDC guideline takes a one-size-fits-all approach to chronic pain -- pain that lasts longer than three months -- and doesn't distinguish between pain from fibromyalgia, arthritis, neuropathy or any other medical condition.  

"We’ve contracted with NASEM to conduct a consensus study and issue a report on its findings. This work will begin with an identification and prioritization of procedures and conditions associated with acute pain for which opioid analgesics are commonly prescribed and where evidence-based clinical practice guidelines would help inform prescribing practices," Gottlieb said in a statement.

"We acknowledge the work of our colleagues at the U.S. Centers for Disease Control and Prevention (CDC) who have taken an initial step in developing federal guidelines on pain management and the use of opioids which are based on expert opinion. Our work seeks to build on that work by generating evidence-based guidelines where needed. The guidelines we generate would be distinct from this corresponding effort by the CDC, in that our effort would be indication-specific." 

Importantly, Gottlieb says NASEM will hold a series of public meetings and workshops, and seek input from "a broad range of stakeholders" from different medical specialties. The CDC guideline was initially developed with no public hearings and with little input from pain management experts.

While Gottlieb clearly wants more transparency brought to the guideline development process, he also clings to the notion that opioid medication is overprescribed and is primarily responsible for the nation's opioid crisis.

"Many people who become addicted to opioids will first be exposed to these drugs through a lawfully prescribed medication. Unfortunately, the fact remains that there are still too many prescriptions being written for opioids," Gottlieb said.

"Our analyses suggest that the first prescription for many common, acute indications could typically be for many fewer pills – maybe just a day or two of medication rather than a 30-day supply, which is typically prescribed. In some cases, the excess pills that aren’t used by patients may end up being diverted to illicit markets or misused or abused by friends or family members. In other cases, patients who are prescribed more medication than necessary may find themselves at increased risks for misuse, abuse and addiction."

But studies show that long-term opioid use by patients recovering from surgery is rare and less than one percent of legally prescribed opioids are diverted.

In 2016, the American Pain Society released guidelines that encourage physicians to limit the use of opioids and offer “multimodal therapies” to patients suffering from postoperative pain. Among the treatments suggested are pregabalin, gabapentin, NSAIDs and acetaminophen.

The University of Michigan has also developed prescribing guidelines for over a dozen common surgeries, ranging from hernia repair to hysterectomies. The recommendations list the suggested dose of opioids and number of pills for each procedure.      

Several states have already adopted their own guidelines for acute pain, limiting opioids to a few days' supply -- regardless of whether the pain is from a broken leg, a tonsillectomy or gunshot wound.  It's not clear how federal guidelines for acute pain would impact state regulations.

Studies Warn of Pregabalin Deaths

By Pat Anson, Editor

Two new studies – one in Canada and one in Australia – should give pause to patients who use opioids and pregabalin (Lyrica), an anticonvulsant medication increasingly prescribed for fibromyalgia, neuropathy and other chronic pain conditions. Both studies found a number of overdose deaths that involve – but were not necessarily caused -- by pregabalin.

The Canadian study, published in the Annals of Internal Medicine, looked at over 1,400 patients in Ontario on opioid medication from 1997 to 2016 who died from opioid-related causes. Another group of over 5,000 surviving opioid patients was used as a control group.

Researchers found that patients who were co-prescribed opioids and pregabalin had a significantly higher risk of an overdose.

The risk of death was over two times higher for patients receiving opioids and a high dose of pregabalin (over 300mg) compared to those who took opioids alone.

Patients on a low or moderate dose of pregabalin also had a heightened risk, although not as large.

Researchers say pregabalin has a sedative effect and may interact with opioids in ways that increase respiratory depression. Few doctors and patients are aware of the risk, even though over half of Ontario residents who begin pregabalin therapy are also prescribed an opioid.

"There is an important drug interaction between opioids and pregabalin that can lead to increased risk of fatal overdose, particularly at high doses of pregabalin," lead author Tara Gomes, PhD, of the Institute for Clinical Evaluative Sciences (ICES) and St. Michael's Hospital in Toronto, told MedPage Today.

"Clinicians should consider carefully whether to prescribe opioids and pregabalin together. If they decide that both medications are clinically appropriate, they should start with low doses and monitor their patients closely."

Lyrica (pregabalin) and Neurontin (gabapentin) are both made by Pfizer and belong to a class of anticonvulsant nerve medication called gabapentinoids. Sales of gabapentinoids have tripled in recent years, in part because of CDC prescribing guidelines that recommend the drugs as alternatives to opioid medication.  

U.S. health officials have only recently started looking into the misuse and abuse of gabapentinoids, which are increasingly used by addicts to enhance the euphoric effects of heroin and other illicit opioids. While gabapentin  has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

“Although current product monographs for gabapentin contain warnings about serious adverse events when this agent is combined with opioids, those for pregabalin do not. The importance of our finding warrants a revision of the pregabalin product monographs,” wrote Gomes.

Pregabalin Abuse in Australia

Health officials in Australia are also concerned about the growing use of pregabalin.  Researchers at the NSW Poisons Information Centre say poisoning cases involving pregabalin rose from zero in 2005 to 376 cases in 2016.

“Our study shows a clear correlation between the rapid and continuous rise of pregabalin dispensing and an increase in intentional poisonings and deaths associated with pregabalin,” said lead author Dr. Rose Cairns, a specialist at the NSW Poisons Information Centre.

According to the Australian Journal of Pharmacy (AJP), there have been 88 recorded deaths associated with pregabalin in recent years. Most of the deaths involved young, unemployed males who had a history of substance abuse, particularly with opioids, benzodiazepines, alcohol and illicit drugs.

“We believe that Australian doctors may not be aware of the abuse potential of pregabalin,” Cairns said. “Most patients who are prescribed this medication are in the older population but the group who are at high risk of overdosing are much younger. These people are likely to have been prescribed pregabalin despite having a history of substance abuse.”

According to researchers, up to two-thirds of people who intentionally misused pregabalin had a prior documented substance abuse history. “Prescribers need to consider this growing body of evidence that pregabalin has abuse potential before prescribing, especially to patients with substance abuse history,” said Cairns.

Pfizer did not respond to a request for comment on the Canadian and Australian studies.

Study Finds Racial Bias in Drug Testing

By Pat Anson, Editor

African-American patients on long-term opioid therapy are more likely to be drug tested by their doctors and significantly more likely to have their opioid prescriptions stopped if an illicit drug is detected, according to a new study.

Yale researchers analyzed the health records of more than 15,000 patients who received opioids from the Veterans Administration between 2000 and 2010. About half of the VA patients were white and half black.

Over 25 percent of the black patients had a urine drug test within the first six months of opioid treatment, compared to nearly 16% of whites.

When patients tested positive for either marijuana or cocaine, the vast majority – 90 percent -- continued to receive their opioid prescriptions. But there were significant differences in how patients were treated depending on their race.

Black patients that tested positive for marijuana were twice as likely as whites to have opioid therapy stopped and three times more likely to have opioids discontinued if cocaine was detected in their urine.

The findings, published in the journal Drug and Alcohol Dependence, are consistent with previous research showing disparities in how blacks and whites are treated by the healthcare system in general, and particularly when opioids are involved.

“There is no mandate to immediately stop a patient from taking prescription opioids if they test positive for illicit drugs,” said first author Julie Gaither, PhD, a pediatrics instructor at the Yale School of Medicine.

“It’s our feeling that without clear guidance, physicians are falling back on ingrained stereotypes, including racial stereotyping. When faced with evidence of illicit drug use, clinicians are more likely to discontinue opioids when a patient is black, even though research has shown that whites are the group at highest risk for overdose and death.”

A 2016 study of emergency room patients found that blacks were significantly less likely to get an opioid for abdominal pain than whites. Another study of white medical students and residents found that half had at least one false belief about black patients. Those that did were more likely to report lower pain ratings for black patients.

Drug Testing for Marijuana Not Recommended

The 2016 CDC opioid guideline encourages doctors to conduct urine drug tests before starting opioid therapy and at least annually after patients start taking the drugs. But the guideline also urges physicians not to test opioid patients for tetrahyrdocannabinol (THC), the psychoactive ingredient in marijuana that makes people high.

“Clinicians should not test for substances for which results would not affect patient management or for which implications for patient management are unclear. For example, experts noted that there might be uncertainty about the clinical implications of a positive urine drug test for tetrahyrdocannabinol (THC).” the guideline states.

"Clinicians should not dismiss patients from care based on a urine drug test result because this could constitute patient abandonment and could have adverse consequences for patient safety, potentially including the patient obtaining opioids from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder."

Another factor to consider is the unreliability of urine drug tests. As PNN has reported, “point-of care” (POC) urine drug tests, the kind widely used in doctor’s offices, frequently giving false positive or false negative results for marijuana, cocaine and other drugs. 

A 2015 study found that 21% of POC tests for marijuana and 12% of those for cocaine produced a false positive result.

Message to CDC: Tear Down Your Walls of Silence!

By Richard Lawhern, PhD, Guest Columnist

In March 2016, the Centers for Disease Control and Prevention published its guideline for primary care physicians on prescribing opioid medication for chronic non-cancer pain.

Three months before its publication, Congress and President Obama made the guideline mandatory for the Veterans Health Administration, leading to revised practice standards at the VA that sharply restrict opioid medication for all veterans, regardless of risk or benefit. These unjustified restrictions were again written into federal law by the Veterans Administration Mission Act and recently signed into law by President Trump.

In civilian practice -- and despite being phrased as voluntary and only for general practitioners -- the CDC guideline was immediately and widely interpreted as a mandatory standard of practice for all doctors. 

Many insurers and healthcare providers adopted the CDC’s 90mg morphine equivalent dose (MME) as the maximum safe level of treatment, and some states have limited opioids to 7 days' supply or less for initial prescriptions, even after major surgery. 

More recently, Oregon’s Medicaid program has proposed rule changes that would forcibly taper many chronic pain patients currently on opioid therapy to zero. 

Major changes are also coming next year for Medicare patients nationwide that will sharply restrict high-dose opioid therapy for hundreds of thousands of older and disabled patients, by allowing insurers to require prior authorization for prescriptions in excess of 200 MMEs.

Almost immediately -- and despite wording in the CDC guideline discouraging such action -- doctors began coercing patients to eliminate or reduce opioids that were effective in managing their pain for years. State and federal law enforcement agencies like the Drug Enforcement Administration also ramped up the investigation and prosecution of doctors who prescribe high doses. 

Fearing loss of their livelihoods, many doctors refused to prescribe opioids or discharged patients who asked for them.  Some physicians left pain practice altogether.  As a result, tens of thousands of patients can no longer find effective pain treatment. There are widespread stories in social media, acknowledged in professional medical literature, of patients deserted by doctors who spiral down into agony, disability, and in some cases suicide. 

Where is CDC’s Guideline Evaluation?

One would think that federal agencies that caused such a public health disaster would be concerned with correcting course.  But that is not the case. 

Practice standards published by medical associations usually include a follow-up program to measure their safety and effectiveness. However, CDC has failed to conduct a full assessment of the opioid guideline in the nearly two and a half years since its release – even though the agency pledged in the guideline to conduct one:

“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.”

It is obvious why the CDC has maintained a wall of silence in the face of widespread criticism of the guideline by both patients and doctors. The agency is desperately wrong on three central assumptions about the opioid crisis:

1. The crisis was caused by “over-prescribing” medical opioids to patients in pain. Doctors were careless, greedy or deceived by evil pharmaceutical companies into ignoring risks of drug addiction.
2. There is no evidence that opioid analgesics are effective for pain when used over long periods.
3. Alternative pain therapies and non-opioid medications are safer and more effective than opioids and should be preferred over them.

All three of these assumptions are wrong.  Patient experience and published data from healthcare researchers demonstrate they are wrong. Let’s look at these three false assumptions.

Do Opioid Prescriptions Cause Overdose Deaths? 

Very rarely.  If prescribing increases the risk of opioid overdose deaths, then we would expect to see more overdoses in states and patient demographic groups where prescribing rates are highest.  But we do not. 

The following graphic compares overdose mortality rates from legal and illegal opioids to rates of opioid prescribing in all 50 states and Washington, DC in 2016.

SOURCE: CDC DATABASE

It might be difficult for a layman to make much sense of this graphic.  And that is precisely the point.  If there was a clear cause and effect relationship between prescribing and overdose deaths, then we would see higher death rates on the right side of the chart, with most data clumped closely around a rising central trend line.  But we don’t see that. 

The contribution of medically prescribed opioids to overdose deaths is so small that it gets lost in the noise of illegal street drugs.  Contrary to the screaming headlines in the media, prescription drugs aren’t killing people in large numbers. Illegal street drugs are.

This is not to say prescription drugs played no role in worsening the opioid crisis.  But in recent years, their role in opioid mortality has become small.  Even when they are found in the bloodstream of an overdose victim, opioid prescriptions are almost never found alone.  In Massachusetts, illicit fentanyl was found last year in 85% of blood toxicology screens of overdose victims, while heroin and/or cocaine were detected in about 45% of them.  Prescription opioids were found in only 15% of overdose victims.

Those numbers obviously don’t add up to 100 percent.  That is because the great majority of overdose victims had taken more than one illegal drug plus alcohol and/or benzodiazepine drugs.  We don’t really know which drug or combination of drugs caused the overdose.   

Overdose data also suggest that death is not a predictable outcome of opioid prescribing, nor is it common in groups that use the most opioid prescriptions. 

Basic trends in the chart below stand out.  First, rates of overdose deaths among people over age 50 have been stable for the last 17 years, while death rates among young people have risen sharply. In 2016, they were six times higher than in seniors.

We know that rates of opioid prescribing for seniors are at least 250% higher than for kids under 21. Thus, the group that benefited the most from liberalized prescribing policies of a decade ago – older adults -- has shown no higher risk of overdose deaths, even as kids who receive fewer opioid prescriptions are now dying in record numbers.

The asserted demographics of “over-prescribing” are plainly wrong. They don’t work and never have.  Exposure to medically managed opioids does not cause increased opioid mortality, at least not directly. 

Brief exposure to prescription opioids contributes very little to addiction or long term use. In two recent large-scale studies, opioid abuse and prolonged prescribing of opioids were evaluated for over 650,000 patients given opioids for the first time to control pain after surgery.  Fewer than 0.6% of these patients were diagnosed with opioid abuse 2.5 years later. 

This means that opioid treatment for acute pain is safe, effective and usually free of bad outcomes for over 99% of opioid-naive post-surgical patients.

Do Opioid Medications Relieve Chronic Pain?

Of course they do!

We hear a lot of noise that there is no evidence or proof that opioids work for long periods.  But “no proof” is not the same as “proof of no effect”. 

There are very few double blind clinical trials for opioids longer than 90 days -- and this reality is entirely understandable.  When people with severe pain are given placebos, they lapse into agony and drop out of trials.  Long term studies of any pain treatment can easily rise to the level of being inhumane – which is why so few have been conducted.

It isn’t rocket science, and the writers of the CDC guideline knew it.  Instead of comparing shorter trials of opioid analgesics against behavioral therapies and non-opioid medications, the guideline writers stacked the deck against opioids.  And they got caught at it by their medical peers. 

If trials of all three therapies had been limited to studies of at least a year -- as opioids were but alternative therapies were not -- none of the three could have provided “evidence” of useful effect.

We must also acknowledge that not all patients do well on opioids.  Some develop persistent nausea, sedation, constipation, suppression of sexual libido and depression. Some patients also become drug tolerant, requiring ever-increasing doses of opioids to achieve the same pain-relieving effects.  It has been theorized that a condition called “opioid induced hyperalgesia” may alter the action of opioid receptors in the brain.  But there is no medical consensus on how to measure such an effect in human beings, or even whether hyperalgesia exists. 

Many of the perceived failures of opioid therapy might be laid at the feet of ill-trained physicians.  Some doctors titrate their patients from zero to a therapeutic dose too fast.  Others fail to recognize factors in liver metabolism which make some patients poor metabolizers or hyper-metabolizers of opioids. Variation in metabolism means that there can be no one-size-fits-all pain treatment. Opioid therapy can be safe and effective for a small minority of patients at doses well above 1,000 MME.

Are Safe Substitutes for Opioids Widely Available?

For millions of patients, not yet.

We hear a lot of noise about tapering pain patients out of opioid therapy and into “alternative” or “integrative medicine.”  Indeed, it seems appropriate to first try less powerful medications such as NSAIDs or anticonvulsants before proceeding to opioids.  Exercise and massage therapy are also useful as palliative therapies.  But for millions of people, less powerful medications don’t work well enough -- or at all.  Tylenol or ibuprofen at high doses might also put you in a hospital with liver toxicity or major gastrointestinal problems.

What about “non-pharmacological” and “non-invasive” therapies?  Do they work well enough to be substituted for opioids?  Unfortunately, the answer is no. The state of science for alternatives like cognitive behavioral therapy, acupuncture, chiropractic, or various talk therapies is simply abysmal. 

At most, these alternative treatments are experimental.  They might be useful as supportive therapies in coordination with a well managed program of pain relieving medications.  But pending a more rigorous evaluation, we simply cannot offer such experimental techniques as substitutes for opioids. 

What Are Federal Agencies Doing to Correct Course?

In two words, “nothing apparent.”

The CDC, Food and Drug Administration, Health and Human Services (HHS), and the National Institutes of Health seem to be collectively dragging their feet in a campaign of deliberate inaction, refusing to respond to criticism or examine their own medical evidence of error.

This author and others have been trying for years to get healthcare agencies to reevaluate the relationship between opioid prescribing and overdose mortality. These efforts have included recent testimony to the FDA Opioid Policy Steering Committee and to the HHS Inter Agency Task Force on Best Practice in Pain Management.

In addition, copies of our analysis have been sent to the following authorities.  Most have been silent and none have responded in substance.

• Dr. Scott Gottlieb, FDA Commissioner and senior analytics staff
• Dr. Sharon Hertz, Director, Division of Anesthesia, Analgesia, and Addiction Products, FDA
• Dr. Mary Kremzner, Director, Division of Drug Information, FDA. (Dr. Kremzner responded with a courteous letter referring to a press release from Scott Gottlieb). 
• Alicia Richmond Scott, Designated Federal Officer, and Dr. Vanilla Singh, Chair of the HHS Inter Agency Task Force on Best Practices in Pain Management  
• Dr. Nora Volkow, Director of the National Institute on Drug Abuse
• The Whistleblower gateway of the House Subcommittee on Government Oversight

An inquiry was also filed online with the CDC. A dismissive response was received from the CDC Center for Injury Prevention – which oversaw development of the opioid guideline -- claiming to have read my analysis and asserting their previous positions.  This response was clearly a brush-off adapted from previous form letters.

A request is now in preparation to the HHS Office of the Inspector General, asking for investigation of CDC for malfeasance and possible fraud.

Richard Lawhern, PhD, has for 21 years volunteered as a patient advocate in online pain communities and a subject matter expert on public policy for medical opioids.  He is co-founder and corresponding secretary of the Alliance for the Treatment of Intractable Pain.

Graphics in this article originally published by The Crime Report on January 21, 2018, in "The Phony War Against Opioids - Some Inconvenient Truths."

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.

Trump Administration Proposes More Rx Opioid Cuts

By Pat Anson, Editor

For the third year in a row, the U.S. Drug Enforcement Administration is proposing another round of cuts in the supply of opioid pain medication – a 10% reduction in manufacturing quotas in 2019 for several widely used opioids.  The Trump Administration says the pain relievers are “frequently misused” and reducing their supply will help prevent addiction and abuse.

The DEA proposal involves six opioids classified as Schedule II controlled substances:  oxycodone, hydrocodone, oxymorphone, hydromorphone, morphine, and fentanyl. Some of the medications are already in short supply, forcing some hospitals to use other pain relievers to treat surgery and trauma patients.

“President Trump has set the ambitious goal of reducing opioid prescription rates by one-third in three years. We embrace that goal and are resolutely committed to reaching it,” Attorney General Jeff Sessions said in a statement. “We have already made significant progress in reducing prescription rates over the past year. Cutting opioid production quotas by an average of ten percent next year will help us continue that progress and make it harder to divert these drugs for abuse.”

The DEA has already made substantial cuts in opioid production quotas, reducing them by 25 percent in 2017, followed by another 20 percent cut in 2018.  

The production cuts have had no effect on reducing the nation’s soaring overdose rate. According to a preliminary report released this week by the CDC, over 72,000 Americans died of drug overdoses last year, a 6 percent increase from 2016. The rising death toll is primarily attributed to illicit fentanyl, heroin and cocaine. Overdoses involving prescription opioids appear to have leveled off.

The DEA’s latest round of production cuts is in line with President Trump’s “Safe Prescribing Plan” which seeks to reduce "the over-prescription of opioids” by cutting nationwide opioid prescription fills by one-third within three years.

“We’ve lost too many lives to the opioid epidemic and families and communities suffer tragic consequences every day,” said DEA Acting Administrator Uttam Dhillon. “This significant drop in prescriptions by doctors and DEA’s production quota adjustment will continue to reduce the amount of drugs available for illicit diversion and abuse while ensuring that patients will continue to have access to proper medicine.”

‘Serious Consequences’ for Patients

But legitimate patients are losing access to opioids.  Many hospitals and hospices now face a chronic shortage of three intravenous or injectable opioids --  morphine, hydromorphone and fentanyl -- which are used to treat patients recovering from surgery or trauma. Shortages of these "parenteral" drugs have been primarily blamed on manufacturing problems, although some critics say it has been worsened by the DEA production cuts.

“The shortage has serious consequences for patients and physicians. Parenteral opioids provide fast and reliable analgesia for patients admitted to the hospital with poorly controlled pain, patients who have undergone painful procedures such as major surgery, and those who were previously on oral opioid regimens but are unable to continue treatment by mouth,” Edward Bruera, MD, an oncologist at The University of Texas MD Anderson Cancer Center, wrote in an op/ed published this week in The New England Journal of Medicine.

“Shortages of the three best-known parenteral opioids may increase the risk for medication errors when it becomes necessary to switch a patient to a less familiar drug or to use opioid-sparing drug combinations. Opioids are already among the drugs most frequently involved in medication errors in hospitals. There are also increased risks of delayed time to analgesia and of side effects resulting in unnecessary patient suffering and delayed hospital discharge.”

Although opioid prescribing guidelines are only intended for physicians treating patients with “chronic non-cancer pain,” Bruera says some cancer patients are being affected by opioid shortages and over-zealous enforcement of prescribing guidelines.

“Most hospitalized patients and almost all patients with cancer need opioids, either on a temporary basis after surgery or painful treatments such as stem-cell transplantation, or longer for cancer-related pain or dyspnea,” he wrote. “It is impossible to appropriately treat such a large number of patients unless most physicians are able and willing to prescribe opioids. There were not enough palliative care and pain specialists to meet patient needs before the shortages began, and universal referral of patients who need parenteral opioids will therefore only result in more undertreated pain.”

The rationale behind the DEA’s production cuts defy some of the agency’s own analysis. Less than one percent of legally prescribed opioids are diverted, according to a 2017 DEA report, which also found that admissions for painkiller abuse to publicly funded addiction treatment facilities have declined significantly since 2011, the same year that opioid prescriptions began dropping.

Positive Results for New Osteoarthritis Drug

By Pat Anson, Editor

Two pharmaceutical companies have announced positive results from a Phase 3 study of an experimental non-opioid pain reliever that has a history of safety concerns.

Teva and Regeneron are jointly developing fasinumab as a treatment for chronic pain from osteoarthritis of the knee and hip. The companies say patients treated for 16 weeks with fasinumab injections had significantly less pain and improved function compared to a placebo.

"We are encouraged by these data and look forward to advancing our pivotal Phase 3 fasinumab program in patients with osteoarthritis of the knee or hip, who currently have very limited therapeutic choices to treat their chronic pain, other than with non-steriodal anti-inflammatory drugs or opioids," said George Yancopoulos, MD, President and Chief Scientific Officer of Regeneron.

Fasinumab is a humanized antibody that targets nerve growth factor (NGF), a protein that increases in the body because of injury, inflammation or chronic pain. Fasinumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

Teva and Regeneron say fasinumab was “generally well tolerated” in the Phase 3 study, with similar adverse events (AEs) as in previous trials. Treatment was discontinued due to AEs in 6 percent of the fasinumab patients, about the same as the placebo group. The companies plan to present further details at an upcoming medical conference.

Regeneron recently halted high-dose trials of fasinumab because the risk of harm outweighed the benefits of the drug. There is some concern that NGF antibodies work too well and encourage osteoarthritis patients to become more active, which accelerates joint deterioration. No cases of joint damage were observed in the current study.

Regeneron and Teva are currently enrolling osteoarthritis patients in three additional Phase 3 clinical trials, including one assessing the long-term safety of fasinumab and two trials comparing fasinumab to standard pain therapies.

There is intense competition about drug companies to develop non-opioid pain relievers that don’t have the risk of addiction and overdose. Pfizer and Eli Lilly are jointly developing a similar NGF inhibitor called tanezumab, which was given fast track designation by the FDA in 2017 to speed its development.

Like fasinumab, there are safety concerns about tanezumab. The FDA ordered a partial halt to clinical studies of tanezumab in 2010 after Pfizer said a small number of osteoarthritis patients taking the drug needed joint replacements. Another safety issue arose in 2012 because the drug caused “adverse changes in the sympathetic nervous system of mature animals.”  Most clinical studies of tanezumab did not resume until 2015.

FDA Warns Veterinarians of Pet Owners Abusing Opioids

By Pat Anson, Editor

Doctors and patients aren’t the only ones under scrutiny for prescribing and using opioid pain medication. Pet owners are also coming under suspicion for diverting and abusing opioids intended for their animals.

The Food and Drug Administration today warned veterinarians to be cautious when prescribing opioids and be on the alert for people who may be using their pets to gain access to the drugs.

“We recognize that opioids and other pain medications have a legitimate and important role in treating pain in animals – just as they do for people,” FDA commissioner Scott Gottlieb, MD, said in a statement.

“But just like the opioid medications used in humans, these drugs have potentially serious risks, not just for the animal patients, but also because of their potential to lead to addiction, abuse and overdose in humans who may divert them for their own use.”

Only one opioid is currently approved by the FDA for use in animals, a potent fentanyl medication for post-surgical pain that is sold under the brand name Recuvyra.  

The maker of another fentanyl based product -- carfentanil -- voluntarily surrendered approval for the drug in March because of growing signs it was being diverted. Carfentanil is so potent it was used by veterinarians as an anesthetic on elephants.   

With few options to choose from, some veterinarians are legally prescribing tramadol and others opioids intended for humans to relieve pain in pets. The FDA is recommending veterinarians use alternatives to opioids whenever possible and look for signs of opioid abuse by pet owners and their own employees.

“We’re advising veterinarians to develop a safety plan in the event they encounter a situation involving opioid diversion or clients seeking opioids under the guise of treating their pets; and taking steps to help veterinarians spot the signs of opioid abuse,” Gottlieb said.

Possible warning signs of opioid abuse are suspicious injuries to animals, a pet owner asking for specific medication by name, or asking for refills of lost or stolen medication.

Gottlieb’s statement was released one week after a small study published in the American Journal of Public Health suggested that some pet owners are purposely injuring their animals to gain access to opioids.

"Our results indicate that we should be paying more attention to how opioid abusers are seeking their drugs -- including through veterinary clinics," said Lili Tenney, deputy director of the Center for Health, Work & Environment at the Colorado School of Public Health.

In a survey of 189 Colorado veterinarians, 13 percent reported they had seen a client who they believed had purposefully injured a pet or made them ill. Nearly half the vets said they knew of a pet owner or employee who was abusing opioids; and 12 percent suspected a staff member of diverting opioids or abusing them.

Colorado and Maine require veterinarians to look at a pet owner’s medication history before dispensing opioids or writing a prescription.  Over a dozen states require veterinarians to report when they prescribe opioids to a prescription drug database.

The New Face of the Opioid Crisis

By Pat Anson, Editor

Caylee Cresta doesn’t have any illusions about being the next Internet star or YouTube sensation. But the 23-minute video she posted on what it’s like to be a chronic pain patient during an age of opioid hysteria has become a hit in the pain community.

“This video should be made to go viral,” one fan said.

“Caylee you did an amazing, persuasive presentation. Maybe you should be a lobbyist!” another one wrote.

“Single best piece of chronic pain patient advocacy I have ever seen. Absolutely brilliant!” wrote Chuck Malinowski.

Caylee’s video is not addressed to the pain community, but to the public at large. The 26-year old Massachusetts woman with fiery red hair looks directly into the camera and earnestly asks people to set aside their misconceptions about pain, addiction and the opioid crisis.

“I do not suffer from addiction and yet stigma will tell you that I do.  And that is a myth that we are going to change,” she says. “Don’t ever brush off the plight of the chronically ill because your lives can change in an instant, just as ours have.

“The fight against opiates is an uneducated one. This is a movement that lacks understanding in its most basic form. Every lawmaker is taking on this fight without ever consulting even a single chronically ill person. What does that mean? That means that the people who depend on these medications aren’t even being considered when taking them away.”

In her video, Caylee spends little time discussing her own experience as a pain patient. While still in high school, Caylee developed a rare and incurable neurological disorder called Stiff-person syndrome, which is characterized by strong muscle spasms and stiffness. The spams are so severe her lungs have collapsed twice.

“I’ll get such strong spasms in my throat and chest cavity that they create so much air that can’t escape (my lungs) that it just made them literally pop,” she told PNN. “My muscle spasms can break my bones, they’ll get that strong.”

Caylee’s symptoms were usually dismissed by doctors and it took years for her to get a proper diagnosis. Last year, a doctor at a pain clinic dropped her as a patient after getting a warning letter from Medicare that she was prescribing too many opioids. Caylee went without opioids for months, which is when her lungs burst.

Living in Fear

Although Massachusetts has a reputation as having some of the best healthcare in the world, Caylee now drives 3 hours one-way to see a neurologist in Connecticut.

“Any other doctor that I’ve seen over the years has literally looked at me and in one way or another and said, ‘Your prognosis is so dim. It’s so rare.’ They’re not even willing to take me on as a patient. My doctor has stuck by me and tried everything there is to try,” she says. 

Caylee has tried stem cells, chemotherapy and many other treatments. The only thing that works is opioid medication. Although she is once again able to get prescriptions for opioids, she often has trouble getting them filled. She and her husband went to 20 pharmacies one day before finding a pharmacist willing to fill her script.

“You live every single day in fear.  Every time you fill your prescription you go, okay, I’m going to have a life for another month. But you live that whole month with such anxiety and wondering what’s going to happen next,” she said. 

Caylee hopes her YouTube video will help educate the public about the daily challenges of being in pain and give some hope to pain sufferers.

“I want to fight for people going through this. I truly want to fight for them. I just want to let people know that they’re not alone. I want them to know that we’re all in this together,” says Caylee.

“What is probably the most humbling is when I get messages like ‘I would do anything for the world to be able to see this’ or ‘I would do anything for this to go viral and for people to understand what we go through.’ When I get messages like that, that let me know that these people feel like somebody is speaking for them, that touches me in a way that I can’t even explain.”

Long-Term Opioid Use Rare After Wisdom Teeth Removed

By Pat Anson, Editor

Anti-opioid activists have long claimed that thousands of young people have become addicted to opioid pain medication after having their wisdom teeth removed.

“Would you give your child heroin to remove a wisdom tooth?” is how a provocative 2016 anti-opioid billboard in New York City’s Times Square put it.

But a large new study published in JAMA found that the risk of long-term opioid use after wisdom tooth removal is relatively rare – although still a cause for concern.

The study of over 70,000 teens and young adults found that only 1.3% were still being prescribed opioids months after their initial prescription by a dentist. The risk of long-term use was nearly 3 times higher for young people prescribed opioids than for those who were not (0.5%).

Although the overall risk of long-term use is small, researchers say the sheer number of wisdom tooth removals warrants caution when prescribing opioids.

"Wisdom tooth extraction is performed 3.5 million times a year in the United States, and many dentists routinely prescribe opioids in case patients need it for post-procedure pain," said lead author Calista Harbaugh, MD, a research fellow and surgical resident at the University of Michigan’s Institute for Healthcare Policy and Innovation.

"Until now, we haven't had data on the long-term risks of opioid use after wisdom tooth extraction. We now see that a sizable number go on to fill opioid prescriptions long after we would expect they would need for recovery, and the main predictor of persistent use is whether or not they fill that initial prescription."

Harbaugh and her colleagues looked at insurance claims for opioid prescriptions between 2009 and 2015. Hydrocodone (70%) was the most common opioid prescribed after wisdom tooth removal, followed by oxycodone (24%). Long-term opioid use was defined as two or more prescriptions filled in the year after wisdom tooth removal.

But other factors besides dental surgery raised the risk of long-term opioid use. Teens and young adults who had a history of chronic pain or mental health issues such as depression and anxiety were more likely to go on to regular use after filling their initial opioid prescription.

"These are some of the first data to the show long-term ill effects of routine opioid prescribing after tooth extractions. When taken together with the previous studies showing that opioids are not helpful in these cases, dentists and oral surgeons should stop routinely prescribing opioids for wisdom tooth extractions and likely other common dental procedures," said senior author Chad Brummett, MD, co-director of the Michigan Opioid Prescribing and Engagement Network.

There are no specific prescribing guidelines for wisdom tooth removal. The American Dental Association recommends that dentists first consider non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief. It also supports the CDC opioid guidelines, which recommend that opioids be limited to no more than 7 days' supply for acute pain.

A small 2016 study found that over half the opioids prescribed to patients after wisdom tooth removal or dental surgery go unused, with many of the leftover pills being abused or stolen by friends and family members. On average, dental patients received 28 opioid pills and – three weeks later – most had pills leftover.

How Common Is Opioid Addiction?

By Roger Chriss, PNN Columnist

As the opioid crisis continues to worsen, there is increased scrutiny of both prescribing levels and fatal overdose rates. The goal of reducing opioid prescriptions is to decrease the exposure to opioids, on the theory that medical use of opioid analgesics is closely linked with addiction and overdose risk.

But how valid is that theory? A key issue in the crisis is opioid addiction rates, which can be divided into medical and non-medical addiction.

Medical Opioid Addiction Rates

The National Institute on Drug Abuse (NIDA) reports that 8 to 12% of patients on long-term opioid therapy develop an opioid use disorder.

“The best and most recent estimate of the percentage of patients who will develop an addiction after being prescribed an opioid analgesic for long-term management of their chronic pain stands at around 8 percent,” NIDA Director Nora Volkow, MD, told Opioid Watch.

The NIDA estimate is well-researched and widely accepted. But there are other estimates, each with important qualifications.

Cochrane found in a major review of studies of long term opioid therapy for non-cancer pain that only 0.27% of participants were at risk of opioid addiction, abuse or other serious side effects.

In another large study, The BMJ reported that only about 3% of previously opioid naïve patients (new to opioids) continued to use them more than 90 days after major elective surgery.

Other addiction rates include numbers as low as 1% and as high as 40%. But details matter. Much of the difference in addiction rates stems from three factors:

1. How well screened the patient population is

2. How carefully monitored the patients are during opioid therapy

3. How the criteria for opioid use disorder are applied

In other words, a well-screened and closely monitored population of adults with no risk factors may well have an addiction rate of 1%. The recent SPACE study by Erin Krebs, MD, in which over 100 people with knee osteoarthritis and low back pain were put on opioid therapy for a year, saw no signs of misuse, abuse or addiction. There were also no overdoses.

Non-Medical Opioid Addiction Rates

It’s also important to look at the percentage of people who become addicted to opioids without ever having an opioid prescription. Here the addiction rates are much higher.

A 2009 study in the American Journal of Psychiatry found that among treatment-seeking individuals who used OxyContin, 78% had not been prescribed the drug for any medical reason. The OxyContin was “most frequently obtained from nonmedical sources as part of a broader and longer-term pattern of multiple substance abuse.”  

The 2014 National Survey on Drug Use also found that about 75% of all opioid misuse starts outside medical care, with over half of opioid abusers reporting that the drugs were obtained “from a friend or relative for free.”

Heroin is considered highly addictive, with nearly one in four heroin users becoming dependent. Importantly, most people who try heroin already have extensive experience with other substances, including opioid medication, and many have serious mental illness. There is no research on the addictive potential of heroin in drug-naive people.

Relatively little is known about the complex and concealed world of nonmedical opioid use. Researchers like UCSF’s Daniel Cicerone are working to fill this gap by collecting information on overdoses to get a more accurate picture on the type of opioids being used.  

Risk Management

Opioids remain an essential part of modern medicine, from trauma and battlefield medicine to surgery, end-of-life care and long-term management of chronic, progressive degenerative conditions. This makes risk management vital.

Current tools to screen patients include the long-standing COMM tool and the new NIDA TAPS tool. Novel approaches using genetic testing for opioid risk may eventually help clinicians better assess risk, too. And improved data analytics may also help reduce addiction.

"Understanding the pooled effect of risk factors can help physicians develop effective and individualized pain management strategies with a lower risk of prolonged opioid use," says Ara Nazarian, PhD, a researcher at Beth Israel Deaconess Medical Center.

The Krebs SPACE study achieved an admirable level of safety by carefully screening and monitoring patients during opioid therapy. A similar patient-focused approach that acknowledges the low rate of medical opioid addiction and works to minimize it further is likely to bring benefits to both individuals and society at large.

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.

Mayo Clinic: Opioid Prescribing Has Not Changed

By Pat Anson, Editor

Numerous studies have shown that opioid prescriptions are falling. The trend started in 2011 and appears to have accelerated since the release of the CDC’s 2016 opioid prescribing guidelines.

The volume of opioid medication filled last year fell by 12 percent, the largest decline in 25 years, according to the IQVIA Institute.  Prescriptions for hydrocodone – once the most widely prescribed drug in the country – have fallen by a third since their peak. Even the CDC has reported that opioid prescriptions have dropped by about 5% each year between 2012 and 2016.

Anecdotally, many patients tell us opioids are harder, if not impossible, to obtain. Nearly half of the 3,100 patients PNN surveyed last year said they were getting a lower dose. And one in four said they were no longer prescribed opioids.

But according to Mayo Clinic researchers, opioid prescribing hasn't changed that much and remains at high levels. In a study published in the British Medical Journal (BMJ), they report that opioid prescriptions for Medicare and privately insured patients have remained relatively stable over the past few years. And the average daily dose of opioids is well above what it was 10 years ago.

“If you’re hearing the message that prescription opioid use is starting to decline, I think we need to counter that message and say in most populations it really isn’t moving very much.” says lead author Molly Jeffery, PhD, scientific director of the Mayo Clinic Division of Emergency Medicine Research. “Our data suggest not much has changed in prescription opioid use since about five years ago.”

Why the discrepancy? Jeffrey says most of the previous studies only looked at market-level data – the amount of opioids that drug makers reported producing and selling. She and her colleagues dug a little deeper, looking at insurance claims for 48 million U.S. patients between 2007 and 2016.  

Over that 10-year period, the rate of opioid use by privately insured patients remained relatively flat at 6 to 7 percent. The average daily dose for that group, about two pills of 5-milligram oxycodone, remained the same.

The rate of opioid use by Medicare patients 65 and older peaked at 15% in 2010 and decreased slightly to 14% by 2016. Their average daily dose, three 5 mg pills of oxycodone, also remained relatively unchanged.

Rates of opioid use by disabled Medicare patients also haven't changed much, peaking at 41% in 2013 and falling to 39% in 2016. Their average daily dose remains relatively high, about eight 5 mg oxycodone pills. 

“Our research of patient-level data doesn’t show the decline that was found in previous research,” says Jeffery. “We wanted to know how the declines were experienced by individual people. Did fewer people have opioid prescriptions? Did people taking opioids take less over time? When we looked at it that way, we found a different picture.”

The Mayo study includes an interesting disclaimer. While the researchers looked at data from patient insurance claims, they never surveyed or spoke to any patients about their opioid use. The researchers said they would “engage” with patients in future blog posts and press releases.

You can share your views with Molly Jeffery by email at jeffery.molly@mayo.edu or @mollyjeffery on Twitter.

Chronic Pain Patients Caught in Debate Over Opioids

By Will Stone, KJZZ

It started with a rolled ankle during a routine Army training exercise. Shannon Hubbard never imagined it was the prologue to one of the most debilitating pain conditions known to exist, called ­­­­­­­complex regional pain syndrome.

The condition causes the nervous system to go haywire, creating pain disproportionate to the actual injury. It can also affect how the body regulates temperature and blood flow.

For Hubbard, it manifested years ago following surgery on her foot — a common way for it to take hold.

“My leg feels like it’s on fire pretty much all the time. It spreads to different parts of your body,” the 47-year-old veteran said.

Hubbard props up her leg, careful not to graze it against the kitchen table in her home east of Phoenix. It’s red and swollen, still scarred from an ulcer that landed her in the hospital a few months ago.

“That started as a little blister and four days later it was like the size of a baseball,” she said. “They had to cut it open and then it got infected, and because I have blood flow issues, it doesn’t heal.”

She knows it’s likely to happen again.

Over the past three years, I’ve been prescribed over 60 different medications and combinations; none have even touched the pain,” she said.

Hubbard said she’s had injections and even traveled across the country for infusions of ketamine, an anesthetic that can be used for pain in extreme cases. Her doctors have discussed amputating her leg because of the frequency of the infections.

“All I can do is manage the pain,” she said. “Opioids have become the best solution.”

For about nine months, Hubbard was on a combination of short- and long-acting opioids. She said it gave her enough relief to start leaving the house again and do physical therapy.

But in April that changed. At her monthly appointment, her pain doctor informed her the dose was being lowered. “They had to take one of the pills away,” she said.

Hubbard knew the rules were part of Arizona’s new opioid law, which places restrictions on prescribing and limits the maximum dose for most patients. She also knew the law wasn’t supposed to affect her — an existing patient with chronic pain.

Hubbard argued with the doctor, without success. “They didn’t indicate there was any medical reason for cutting me back. It was simply because of the pressure of the opioid rules.”

Her dose was lowered from 100 morphine milligram equivalents daily (MME) to 90, the highest dose allowed for many new patients in Arizona. She said her pain has been “terrible” ever since.

“It just hurts,” she said. “I don’t want to walk, I pretty much don’t want to do anything.”

Hubbard’s condition may be extreme, but her situation isn’t unique. Faced with skyrocketing drug overdoses, states are cracking down on opioid prescribing. Increasingly, some patients with chronic pain like Hubbard say they are becoming collateral damage.

New Limits On Prescribing

More than two dozen states have implemented laws or policies limiting opioid prescriptions in some way. The most common is to restrict a patient’s first prescription to a number of pills that should last a week or less. But some states like Arizona have gone further by placing a ceiling on the maximum dose for most patients.

The Arizona Opioid Epidemic Act, the culmination of months of outreach and planning by state health officials, was passed earlier this year with unanimous support.

It started in June 2017, when Arizona Gov. Doug Ducey, a Republican, declared a public health emergency, citing new data, showing that two people were dying every day in the state from opioid overdoses. He has pledged to come after those responsible for the rising death toll.

He has pledged to come after those responsible for the rising death toll.

“All bad actors will be held accountable — whether they are doctors, manufacturers or just plain drug dealers,” Ducey said in his annual State of the State address, in January 2018.

The governor cited statistics from one rural county where four doctors prescribed 6 million pills in a single year, concluding “something has gone terribly, terribly wrong.”

Later in January, Ducey called a special session of the Arizona legislature and in less than a week he signed the Arizona Opioid Epidemic Act into law. He called it the “most comprehensive and thoughtful package any state has passed to address this issue and crisis to date.”

The law expands access to addiction treatment, ramps up oversight of prescribing and protects drug users who call 911 to report an overdose from prosecution, among other things.

Initially, Arizona’s major medical associations cautioned against what they saw as too much interference in clinical practice, especially since opioid prescriptions were already on the decline.

Gov. Ducey’s administration offered assurances that the law would “maintain access for chronic pain sufferers and others who rely on these drugs.” Restrictions would apply only to new patients. Cancer, trauma, end-of-life and other serious cases were exempt. Ultimately, the medical establishment came out in favor of the law.

Pressure On Doctors

Since the law’s passage, some doctors in Arizona report feeling pressure to lower patient doses, even for patients who have been on stable regimens of opioids for years without trouble.

Dr. Julian Grove knows the nuances of Arizona’s new law better than most physicians. A pain doctor, Grove worked with the state on the prescribing rules.

“We moved the needle to a degree so that many patients wouldn’t be as severely affected,” said Grove, president of the Arizona Pain Society. “But I’ll be the first to say this has certainly caused a lot of patients problems [and] anxiety.”

“Many people who are prescribing medications have moved to a much more conservative stance and, unfortunately, pain patients are being negatively affected.”

Like many states, Arizona has looked to its prescription-monitoring program as a key tool for tracking overprescribing. State law requires prescribers to check the online database. Report cards are sent out comparing each prescriber to the rest of their cohort. Clinicians consider their scores when deciding how to manage patients’ care, Grove said.

“A lot of practitioners are reducing opioid medications, not from a clinical perspective, but more from a legal and regulatory perspective for fear of investigation,” Grove said. “No practitioner wants to be the highest prescriber.”

Arizona’s new prescribing rules don’t apply to board-certified pain specialists like Grove, who are trained to care for patients with complex chronic pain. But, said Grove, the reality is that doctors — even pain specialists — were already facing pressure on many fronts to curtail opioids — from the Drug Enforcement Agency to health insurers down to state medical boards.

The new state law has only made the reduction of opioids “more fast and furious,” he said.

Grove traces the hypervigilance back to guidelines put out by the Centers for Disease Control and Prevention in 2016. The CDC spelled out the risks associated with higher doses of opioids and advised clinicians when starting a patient on opioids to prescribe the lowest effective dosage.

Psychiatrist Sally Satel, a fellow at the American Enterprise Institute, said those guidelines stipulated the decision to lower a patient’s dose should be decided on a case-by-case basis, not by means of a blanket policy.

“[The guidelines] have been grossly misinterpreted,” Satel said.

The guidelines were not intended for pain specialists, but rather for primary care physicians, a group that accounted for nearly half of all opioids dispensed from 2007 to 2012.

“There is no mandate to reduce doses on people who have been doing well,” Satel said.

In the rush to address the nation’s opioid overdose crisis, she said, the CDC’s guidelines have become the model for many regulators and state legislatures. “It’s a very, very unhealthy, deeply chilled environment in which doctors and patients who have chronic pain can no longer work together,” she said.

Satel called the notion that new prescribing laws will reverse the tide of drug overdose deaths “misguided.”

The rate of opioid prescribing nationally has declined in recent years, though it still soars above the levels of the 1990s. Meanwhile, more people are dying from illicit drugs like heroin and fentanyl than prescription opioids.

In Arizona, more than 1,300 people have died from opioid-related overdoses since June 2017, according to preliminary state numbers. Only a third of those deaths involved just a prescription painkiller.

Heroin is now almost as common as oxycodone in overdose cases in Arizona.

A Range Of Views

Some physicians support the new rules, said Pete Wertheim, executive director of the Arizona Osteopathic Medical Association.

“For some, it has been a welcome relief,” he said. “They feel like it has given them an avenue, a means to confront patients.” Some doctors tell him it’s an opportunity to have a tough conversation with patients they believe to be at risk for addiction or overdose because of the medication.

The organization is striving to educate its members about Arizona’s prescribing rules and the exemptions. But, he said, most doctors now feel the message is clear: “We don’t want you prescribing opioids.”

Long before the law passed, Wertheim said, physicians were already telling him that they had stopped prescribing, because they “didn’t want the liability.”

He worries the current climate around prescribing will drive doctors out of pain management, especially in rural areas. There’s also a fear that some patients who can’t get prescription pills will try stronger street drugs, said Dr. Gerald Harris II, an addiction treatment specialist in Glendale, Ariz.

Harris said he has seen an increase in referrals from doctors concerned that their patients with chronic pain are addicted to opioids. He receives new patients — almost daily, he said — whose doctors have stopped prescribing altogether.

“Their doctor is afraid and he’s cut them off,” Harris said. “Unfortunately, a great many patients turn to street heroin and other drugs to self-medicate because they couldn’t get the medications they need.”

Arizona’s Department of Health Services is working to reassure providers and dispel the myths, said Dr. Cara Christ, who heads the agency and helped design the state’s opioid response. She pointed to the recently launched Opioid Assistance and Referral Line, created to help health care providers with complex cases. The state has also released a set of detailed prescribing guidelines for doctors.

Christ characterizes this as an “adjustment period” while doctors learn the new rules.

“The intent was never to stop prescribers from utilizing opioids,” she said. “It’s really meant to prevent a future generation from developing opioid use disorder, while not impacting current chronic pain patients.”

Christ said she just hasn’t heard of many patients losing access to medicine.

It’s still too early to gauge the law’s success, she said, but opioid prescriptions continue to decline in Arizona.

Arizona saw a 33 percent reduction in the number of opioid prescriptions in April, compared with the same period last year, state data show. Christ’s agency reports that more people are getting help for addiction: There has been about a 40 percent increase in hospitals referring patients for behavioral health treatment following an overdose.

Shannon Hubbard, the woman living with complex regional pain syndrome, considers herself fortunate that her doctors didn’t cut back her painkiller dose even more.

“I’m actually kind of lucky that I have such a severe case because at least they can’t say I’m crazy or it’s in my head,” she said.

Hubbard is well aware that people are dying every day from opioids. One of her family members struggles with heroin addiction and she’s helping raise his daughter. But she’s adamant that there’s a better way to address the crisis.

“What they are doing is not working. They are having no effect on the guy who is on the street shooting heroin and is really in danger of overdosing.” she said. “Instead they are hurting people that are actually helped by the drugs.”

This story is part of a partnership that includes KJZZ, NPR and Kaiser Health News. It is republished with their permission.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.