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The Other Opioid Epidemic

December 30, 2021

Federal crackdowns on opioid prescribing have shifted the crisis from overdoses to undertreatment

The United States is in the grip of an opioid epidemic that has lasted nearly 20 years. During that time, an estimated 400,000 people have died from overdoses that included opioids – either heroin or prescription painkillers.1 "Pill mills," or clinics where doctors unscrupulously hand out prescriptions for powerful opioids like oxycodone, oxycontin, hydrocodone, and fentanyl at volumes far exceeding the need of the patient population, began proliferating in the early 2000s, and have since been one of the main targets of a federal crackdown.

U.S. Drug Enforcement Administration (DEA) agents have arrested doctors and other employees at these facilities, attempting to shut down the steady supply of unnecessary drugs into communities.

Some physicians started to write fewer prescriptions for these painkilling drugs to avoid unwanted attention from law enforcement, and in 2016, the Centers for Disease Control and Prevention (CDC) released new guidelines on prescribing opioids for chronic pain, with restrictions on the amount of painkillers an individual can be prescribed.2 CDC officials noted that the guidelines apply to all adults with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. However, they did not include specific guidance for patients with sickle cell disease (SCD).

Unfortunately, many practitioners took a broader interpretation of the recommendations and began further decreasing their prescriptions for opioids, afraid they'd be found in violation of the guidelines. Some reduced their patients' opioid prescriptions, while others abandoned patients who needed more than the average amount of pain management medications.

These "corrective actions" have helped create a new opioid epidemic, one in which patients with legitimate need for pain medication may be undertreated.

"There is no question that prescriber irresponsibility has contributed to the epidemic," Holly Geyer, MD, an addiction medicine specialist at the Mayo Clinic in Phoenix, Arizona, told ASH Clinical News. "Greater education on the part of physicians and providers is key to preventing future overdoses."

While organizations like the American Society of Hematology (ASH) are encouraging federal agencies to clarify the unique needs of these patient populations and abandon a one-size-fits-all solution to the crisis, hospital networks and individual centers are developing their own strategies for safe, responsible opioid prescribing. ASH Clinical News spoke with Dr. Geyer and other experts in pain management for patients with hematologic disorders to learn about the extent of "the other opioid epidemic."

The Scope of the Epidemic

The beginnings of the opioid epidemic trace back to the 1990s, when what the CDC describes as the first wave of the crisis kicked off with a substantial increase in prescription opioid overdose deaths.1 That was followed by a second wave starting in 2010 that involved rapid increases in heroin overdose deaths. Now, the U.S. has entered a third, deadlier wave, caused primarily by synthetic opioids and illicitly manufactured fentanyl – an extremely potent painkiller. During this time, pill mills and unscrupulous clinicians were able to hand out opioid prescriptions that far exceed patient need with limited oversight, which contributed to increases in patient overdoses and deaths.3

As the opioid epidemic peaked in 2017, the DEA and other law enforcement agencies targeted those clinics and overprescribing physicians.4 State governments began simultaneously tackling the problem from the patient side. Prescription Drug Monitoring Programs use electronic health records to determine whether patients are "doctor shopping" – seeking drugs from multiple prescribers – and visiting multiple pharmacies or filling extra prescriptions.5

While many overdoses occur in individuals using the drugs recreationally, it's clear that overprescribing also has contributed to the epidemic. Over the past few years, though, pharmaceutical companies that manufacture opioids have been accused of deceptive marketing tactics that misled prescribers and patients about their drugs' safety and addictive potential. As of September 2019, multiple manufacturers, including Purdue Pharmaceuticals, Johnson & Johnson, and Allergan, have been fined billions of dollars for their role in fueling the opioid epidemic.6

The reality is that "a good portion of our patients were unfortunately receiving more prescriptions than necessary," said Dr. Geyer. One clear lesson, she added, is that "when we, as providers, don't regulate ourselves, we will be regulated."

Comprehensive, but Restrictive

In July 2016, President Barack Obama signed the Comprehensive Addiction Recovery Act into law. It represented the first major federal addiction legislation in 40 years and allocated $181 million per year to support efforts toward prevention, treatment, recovery, law enforcement, criminal justice reform, and overdose reversal. Among its many sections, the very first, section 101, requested the formation of an "inter-agency task force" led by the U.S. Department of Health and Human Services (HHS) to develop guidelines for safely prescribing medicines to patients with acute and chronic pain.

Earlier this year, the HHS Pain Management Best Practices Inter-Agency Task Force released its final report on acute and chronic pain management best practices, which called for "a balanced, individualized, patient-centered approach."7 This included tailoring pain management to the needs of special populations, such as active-duty military personnel and veterans, children and adolescents, and patients with SCD, cancer-related pain, or receiving palliative care.

Representatives from ASH, the American College of Emergency Physicians, and the Sickle Cell Disease Association of America sent a letter to HHS leaders emphasizing the need to further address pain management in the context of SCD. In response, the HHS leaders described efforts to preserve access to appropriate opioid medications for patients with SCD. These include commissioning an SCD-focused supplement for emergency physicians in the Annals of Emergency Medicine, which is now accepting submissions for articles about complex issues like delays in treatment, patient stigma, provider bias, and access to care. The submission period closes on October 31, 2019.

Regulating the Regulations

"The problem with the CDC guidelines is not the guidelines themselves, but their secondary impact on government agencies like the DEA that look to see if a provider's prescribing meets those guidelines," explained Wally Smith, MD, director of the Virginia Commonwealth University Adult Sickle Cell Program. Since the guidelines were published, some agencies viewed them as concrete rules rather than suggestions, he added.

Again, doctors refused to write opioid prescriptions over fears of fines, or even arrests, given the heightened attention on prescribing patterns. Pharmacists also refused to fill prescriptions, and insurance companies used the guidelines to deny payments for prescriptions that didn't fit within them. "Pharmacies across the U.S. are now adopting a ‘maximum fill' that they apply to specific types of opioids," explained Dr. Geyer. "So, even if we write for a certain amount, there is no guarantee the patient will get it."

According to Dr. Smith, "It is so bad that I had to hire a full-time employee to do nothing but respond to prior authorization requests for opioid prescriptions. It takes an hour per request if you do it by phone. In the meantime, patients in the emergency room are in pain, out of opioids, and in misery," he said.

Not everyone has taken measures like Dr. Smith's. Some pain patients were abandoned by their doctors or abruptly told they would no longer receive opioids. "I don't think the average practitioner is prepared to handle those kinds of cases," Dr. Geyer commented. "Many times, these patients are lost."

"Some providers are not willing to prescribe chronic opioid therapy because of a potential risk," said Amanda Brandow, DO, a hematologist and oncologist at the Children's Hospital of Wisconsin. There is a fear that "the DEA could come to your office because your opioid prescribing patterns have been flagged for some reason."

As a result, some providers scaled back on their opioid prescriptions or put patients on a "forced taper." For example, the 2016 CDC guidelines advised that doctors not increase a patient's opioid dose to more than 90 MME, or morphine milligram equivalents. For the many patients who are already taking higher doses, doctors tapered them back to 90 MME, despite little evidence guiding safe tapering from chronic high doses.8 Patients who have taken opioids for years and developed a physical dependency may be forced to taper, even though they have not shown signs of opioid use disorder and have taken the drugs as prescribed.

"The problem with the CDC guidelines [on prescribing opioids for chronic pain] is not the guidelines themselves, but their secondary impact on government agencies like the DEA."

—Wally Smith, MD

The recent epidemic also has sparked "opiophobia," in patients. Fears of addiction have compelled some patients, even those with legitimate need, to self-impose dosing limits or to forgo opioids for nonaddictive alternatives. Though nonaddictive, these options – including nonsteroidal anti-inflammatories (NSAIDs), antiseizure medications, or nondrug interventions like exercise and massage – may be less effective. Results from a recent meta-analysis of 81 randomized controlled trials comparing placebo with various opioid and nonopioid regimens in patients with chronic cancer pain suggested that lidocaine was the most effective option for pain management, but that assertion was based on just two small studies.9 The second-most effective option was an opioid-containing regimen: codeine plus aspirin.

When patients are refused opioids, the picture gets even bleaker, as research shows that those who are cut off from their medications often turn to illicit sources, risking overdose and death in attempts to quell their pain. An August 2019 study revealed that, for patients who are prescribed opioid therapy for chronic pain, discontinuation did not reduce the risk of death.10 Rather than increasing their survival likelihood, opioid discontinuation tripled the patients' risk of death by overdose.

"There's been so much effort on behalf of states to reduce prescribing," said Dr. Geyer. "What we've created is a very large pool of people who are now seeking their opioids from secondary sources, and that's contributing to the death rate."

The study was published by researchers at the University of Washington, but Dr. Geyer has witnessed that trend in her state, as well. "In Arizona, the death rates have increased independently of our prescribing behaviors improving over the last two years – despite all these regulations," she said. "That speaks to the volume of patients who likely have established opiate use disorders, but who now clearly aren't receiving the necessary treatment for it."

"Some chronic [pain] patients have actually committed suicide because they can't access pain medication," said Dr. Brandow.

Unintended Consequences

It took some time for the effects of the guidelines to become clear, but stakeholders began to push back. In April 2018, ASH released a statement urging consideration of the unintended consequences of increasing regulations on opioid prescribing.11 The Society wrote that, while it supports efforts that increase safe use and monitoring of patients using opioids, "every patient should have access to the approved evidence-based treatments for [his or her] disease and associated symptoms as recommended by [his or her] physician. Patients should not suffer from a lack of recognition of their pain, nor should they have to suffer unnecessary delays in obtaining access to appropriate medications for which there is no effective substitute."

Research supporting that appropriate opioid prescriptions were safe in patients with SCD and cancer continued to pile up: At the American Society of Clinical Oncology's 2018 Quality Care Symposium, investigators found that the general population was 10 times more likely than patients with cancer to die of an opioid overdose.12 "Cancer patients at risk for opioid overdose are different from those at risk in the general population," the authors wrote, "and care should be taken when planning effective treatment of cancer-related pain."

At the 2018 ASH Annual Meeting, researchers also reported that patients with SCD had similar in-hospital mortality rates as the general population, "suggesting that the rate of opioid-related deaths in SCD is low, and the use of opioids for pain control may be considered relatively safe in the SCD population."13

Still, anxiety about the opioid epidemic caused continued restriction of these patients' access to opioids. Between 2016 and 2018, opioid prescriptions decreased from 24% to 10% in patients who had survived cancer and from 48% to 34% in patients with chronic pain, according to a survey from the American Cancer Society's Cancer Action Network.14 More patients also reported difficulty getting their medications, due to issues with pharmacies or insurance companies – up from 11% in 2016 to 30% in 2018.

The person responsible for responsible for coordinating HHS' efforts across the administration to combat the nation's opioid epidemic is HHS Assistant Secretary for Health Adm. Brett Giroir, MD, who leads development of agency-wide public health policy recommendations. Reducing the inappropriate use of opioids is a key priority of his tenure, he told ASH Clinical News, as is preserving access to opioids for patients with SCD or other hematologic conditions who require pain management.

"We must ensure that people living with sickle cell disease don't become collateral damage in the fight against the opioid overdose epidemic," he said. "During a pain crisis, SCD patients often suffer more than they should because of the complex nature and mechanisms of acute and chronic sickle cell pain, combined with a lack of understanding by health care professionals of the unique needs of these patients. We are committed to protecting their access to the appropriate and safe use of opioids, while developing more effective ways to prevent and treat SCD pain."

The HHS inter-agency task force, Dr. Giroir added, is part of these efforts, which starts with educating providers about pain in SCD and other hematologic conditions. "The HHS Pain Management Best Practices Inter-Agency Task Force Report specifically discusses our gaps in knowledge and future areas for research to improve pain management for patients with sickle cell disease," he said.

A New Era of Opioid Guidelines?

Thanks to research demonstrating the safety of opioid prescriptions for pain management in patients with SCD and hematologic malignancies, as well as feedback from ASH and other medical organizations, the CDC issued a key clarification to its 2016 guidelines in April: The recommendations were never intended to deny opioids to patients with cancer- or SCD-related pain.15

ASH applauded this clarification. "People with SCD suffer from severe, chronic pain, which is debilitating on its own without the added burden of having to constantly appeal to the insurance companies every time a pain crisis hits and the initial request is denied," said ASH President Roy Silverstein, MD. "We appreciate the CDC's acknowledgement that the challenges of managing severe and chronic pain in conditions such as SCD require special consideration, and we hope payers will take the CDC's clarification into account to ensure that patients' pain management needs are covered."

When the task force was identifying gaps and inconsistencies in opioid-prescribing knowledge, one challenge became immediately apparent, according to Dr. Brandow, who served on the task force: "No studies assessed the effectiveness of chronic opioid therapy that followed patients beyond six months," she said. "There is a huge gap in the literature, but lack of data does not mean lack of efficacy."

"Regardless of what might have been in their past, it is our moral obligation to manage cancer pain for those who have it."

—Tonya Edwards, MSN, RN

Given the limited empirical evidence, the group suggested that opioid use for chronic pain should be treated on a case-by-case basis. "If patients are benefiting from the therapy, functioning well, and aware of the potential risk-benefit ratio in their individual context, I think that patients should be offered appropriate access to opioid therapy," said Dr. Brandow.

The group also highlighted several examples of patient populations with "unique therapeutic goals" who require careful balancing of risks and benefits in opioid prescribing decisions. SCD was a particularly useful model to discuss pain, Dr. Brandow said, because acute and chronic pain are hallmarks of the disease. "The task force felt that SCD was an outstanding example of a painful condition that basically transcends the entire lifespan," she explained. "It's unique in that regard. It represents all aspects of pain, including acute intermittent pain and chronic pain."

The report stated that SCD patients should likely be considered exempt from the standard guidelines and highlighted how this population frequently experiences health care disparities and racial bias. "Surveys show that SCD is a disparity disease when it comes to accusations of opioid misuse," said Dr. Smith. Patients who present at the emergency room with complaints of pain are often turned away for exhibiting "drug-seeking behavior."

"Physicians are suspicious and may not supply enough opioids. Patients feel very, very mistreated," he added.

Policy in Practice

With this new clarification, hospitals and treatment centers around the country are developing strategies to put policy into practice.

For most providers, that means evaluating a patient's risk for opioid use disorder before writing a prescription. Clinicians take a detailed patient history and use questionnaires like the CAGE Substance Abuse Screening Tool, which asks four questions to determine a patient's potential risk of alcohol or drug abuse.

Still, Tonya Edwards, MSN, RN, a palliative care nurse at the University of Texas MD Anderson Cancer Center, said she gives all patients the benefit of the doubt. "Regardless of what might have been in their past, it is our moral obligation to manage cancer pain for those who have it," she told ASH Clinical News.

Ms. Edwards helped launch the Compassionate High-Alert Team (CHAT) at MD Anderson, a multidisciplinary group comprising clinicians, psychologists, counselors, social workers, and other health care professionals who can address the multiple facets of opioid addiction.

Before CHAT even comes in to play, though, her nursing team educates patients and their caregivers about opioid use, "starting at ‘hello.'" She's worked with practitioners to improve their communication about these issues, so that they can ensure patients and caregivers truly understand their responsibilities. This includes advising them on how to handle difficult situations, like if a patient wakes up with pain in the middle of the night or runs out of painkillers early.

Despite this thorough education, some patients will take more painkillers than they should or get extra prescriptions from other providers. Patients at MD Anderson are monitored carefully, Ms. Edwards noted, and extra prescriptions will show up in the center's Prescription Drug Monitoring Programs database.

When a patient's record shows he or she has run out of drugs early, the patient gets extra prescriptions, she explained. However, if a urine screen comes back and shows that the patient isn't taking the drug – or that he or she is taking a drug not prescribed to the patient – the CHAT team intervenes. The team meets first without the patient to discuss the situation, then they meet with the patient to ask, in a nonconfrontational manner, the circumstances or events that led to the extra prescriptions. After that conversation, the team meets again, without the patient, to discuss appropriate steps forward.

Those steps might include giving the patient fewer medications at a time or increasing the frequency of follow-up visits. "If they can't handle a month's supply maybe we only give them a week's supply," said Ms. Edwards.

Providers also are receiving more education about appropriate screening to help curb the epidemic of overtreatment – and undertreatment for patients with legitimate chronic painkiller needs. ASH recently launched an online repository of Resources for Sickle Cell Disease Pain Management (, which compiles resources for physicians treating patients with SCD. The growing list of material includes links to policy news, pocket guides, and ASH's Consult-a-Colleague program.

When a risk for opioid use disorder is identified, providers like Dr. Smith will often prescribe naloxone, an overdose-reversal drug, along with opioids. Certain states, including Virginia, Vermont, California, Arizona, Florida, Ohio, New Mexico, and Rhode Island now require some of these prescriptions to go hand-in-hand.16 Last year, the U.S. saw the number of deaths from overdose decrease for the first time in a decades.17 CDC officials stated that it could be a result of wider access to naloxone, a finding supported by a study published in JAMA.18

Dr. Smith added that, despite hospitals' and patients' best efforts, addiction happens. In that case, "we try to comanage that," he said. His hospital has a provider authorized to prescribe buprenorphine, a maintenance treatment that can help minimize cravings and relapses in patients with opioid use disorders. New research is showing that it can also be used to treat pain.

Most health care providers are hoping for discoveries of new classes of drugs that might treat pain more safely than opioids can. But until then, researchers are working to find ways to better manage prescriptions for vulnerable patients who need them, but that will take time.

"It takes a very long time to undo something," said Dr. Brandow. It took two or three years for the first CDC guidelines to have an impact, she added. Progress won't happen overnight. â€”By Emma Yasinski


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