Naltrexone Shortage Disrupts Addiction Treatment

By Pat Anson, PNN Editor

An inexpensive drug used to manage chronic pain and treat substance use disorders has joined the growing list of medications that are in short supply in the United States.

The Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) both recently added naltrexone tablets to their drug shortage lists. It’s not clear what caused the shortage, but the ASHP says “there is insufficient supply for usual ordering.”  

Naltrexone is FDA-approved to treat both alcohol and opioid use disorder, and is also used off-label in low doses to treat some chronic pain conditions.

In 50mg doses, naltrexone blocks opioid receptors in the brain and reduces cravings for opiates or alcohol. But in smaller doses of 5mg or less, patients have found low-dose naltrexone (LDN) to be an effective pain reliever for interstitial cystitis, Ehlers-Danlos syndrome, fibromyalgia, and other painful conditions.

LDN advocates believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, the body's natural painkiller. Because it is an opioid antagonist, naltrexone should not be taken with opioid medication.

So far, the shortage only affects 50mg naltrexone tablets. Pain patients usually obtain LDN by prescription from compounding pharmacies, which make the low dose versions in-house.

Several drug makers are reporting short supplies of 50mg tablets, including Accord Healthcare, Major, Elite Laboratories, SpecGx, Sun Pharma, Tagi Pharma, and Avet Pharmaceuticals. The companies didn’t provide the ASHP with a reason for the shortage, but said the tablets are on back order and would be released when they become available.    

The naltrexone shortage comes at an inopportune time, as more people abused alcohol and other substances during the pandemic and sought treatment. The drug that helps them stay sober is now hard to get.

"People are coming in with more cravings," Dr. Aviva Zohar, an addiction medicine provider, told Philly Voice. "Even the feeling of, 'I don't know when my medicine is coming in,' is a huge struggle. It's horrific (and) causing a lot of stress.”

To make up for the shortage, some providers are giving patients Vivitrol, an injectable, extended-release formulation of naltrexone taken once a month. A single Vivitrol injection costs about $1,700, while a month’s supply of 50mg naltrexone tablets costs about $48.

The cheap price of naltrexone may be responsible for the shortage. Most drugs in short supply are low-cost generics with slim profit margins. Some manufacturers have reduced or stopped making generics because they’re not worth the cost of production or the risk of litigation.   

Three generic opioids commonly taken for pain — immediate-release oxycodone, oxycodone-acetaminophen, and hydrocodone-acetaminophen tablets — have been on the ASHP shortage list for nearly a year, with no end in sight.

Prescription Opioids Play Only Minor Role in Overdose Crisis

By Pat Anson, PNN Editor

The role of prescription opioids in the nation’s overdose crisis continues to shrink.

In a new study from the drug testing firm Millennium Health, researchers say multiple substances were found last year in nearly 93% of urine samples in which fentanyl was detected. That is not altogether surprising, as “polysubstance” use increased as fentanyl came to dominate the illicit drug supply, appearing in more and more street drugs such as heroin, cocaine and methamphetamine.

What is surprising is the minimal role that prescription opioids now play. In 2013, opioid pain medication was the most common substance found in fentanyl-positive drug tests in the United States, appearing in over 70% of urine samples.  A decade later, prescription opioids were detected in less than one in ten samples — ranking far behind methamphetamine, cannabis, cocaine and heroin.

In fact, you are about twice as likely to find two other medications -- benzodiazepines (15.8%) and gabapentin (13.3%) -- than you are prescription opioids (7.6%) in urine samples testing positive for fentanyl.

Substances Detected in Fentanyl-Positive Drug Tests (2023)

MILLEnNIUM HEALTH

Millennium based its findings on over 4.1 million urine drug tests (UDTs) collected from 2013 to 2023 and analyzed through mass spectrometry. Because many of those samples came from people being treated for a substance use disorder, they offer a clear insight into drug trends that are driving the overdose crisis.

Now in its “fourth wave,” Millennium says a tidal shift has occurred in the so-called opioid epidemic, with illicit drug users far more likely to use non-opioid substances like stimulants than prescription opioids.

“National, regional, and state-level UDT data all suggest that people who use fentanyl are now, intentionally or unintentionally, much more likely to also use methamphetamine and cocaine,” the report found. “The results of our analyses also reveal shifting patterns of opioid use among those who use fentanyl. More specifically, they showed progressive declines in prescription opioid use from 2015 to 2023.”

The declining role of prescription opioids can be traced back to the 2016 CDC opioid guideline and a multiyear campaign by the DEA to slash opioid production quotas, which has reduced the supply of oxycodone and hydrocodone by about two-thirds. There is little evidence either of those federal efforts reduced the number of overdoses. The CDC estimates there were over 111,000 drug deaths in the 12-month period ending in September 2023 — nearly double the number of fatal overdoses in 2016.

The growing use of stimulants such as methamphetamine makes it difficult for public health campaigns to address the problem. Unlike opioids, there are no FDA-approved medications for stimulant use disorder, leaving behavioral therapies and abstinence as the only “evidence-based” treatments for people with a stimulant problem.

“Stimulants are a serious national challenge emphasizing the need for continued progress on the national plan to address methamphetamine supply, use, and consequences,” Millennium said.

‘Safe Supply’ of Rx Opioids Saved Lives in British Columbia

By Pat Anson, PNN Editor

Prescribing opioids and other medications to people with substance use disorders significantly reduces their risk of dying, according to a large new study in British Columbia. The findings add weight to efforts to create a “safe supply” of legal medications for patients at risk of an overdose from increasingly toxic street drugs.

Vancouver, British Columbia was the first major North American city to be hit by a wave of overdoses involving illicit fentanyl, a potent synthetic opioid. That led Vancouver to become a laboratory for harm reduction programs and safe supply sites offering prescription opioids and injectable heroin to drug users.  

How effective have those programs been?

A study by the B.C. Centre for Disease Control, recently published in the British Medical Journal, found that prescribing opioids, stimulants and anti-anxiety medication to nearly 6,000 drug users dramatically reduced their risk of death.

The Risk Mitigation Guide (RMG) program was initially launched in early 2020 to help drug users going through withdrawal while isolated by the COVID-19 quarantine. A year later, the program was extended, allowing doctors and nurse practitioners to prescribe hydromorphone, morphine, oxycodone, fentanyl, benzodiazepines and stimulants to drug users.

People who were given an initial dose of prescription opioids had a 61% lower risk of death from any cause the following week, and were 55% less likely to die of a drug overdose.

The protective effect of a safe supply increased as more doses were provided. Drug users who received four or more days of opioids were 91% less likely to die from any cause and 89% less likely to die from an overdose.

"We saw a profound impact on reduction in somebody's overdose death risk the week after they picked up these drugs, to a degree that is really surprising and has enormous potential," co-author Paxton Bach, MD, an addiction medicine specialist, told CBC News. "This paper is the strongest evidence we have so far, by a large margin, supporting the idea that this can be an effective strategy for reducing overdose death risk."

But critics of safe supply programs say they don’t really reduce drug abuse. An investigation last year by the National Post found that hydromorphone pills given to drug users in Vancouver were being sold to other addicts, with the sellers then using the money to buy more potent street drugs that were often laced with fentanyl.

A new study in JAMA Internal Medicine also found that opioid-related hospitalizations rose sharply in British Columbia after safe supply programs were launched there, although there was no significant change in overdose deaths. The spike in hospitalizations may have been due to more potent street drugs and counterfeit pills on the black market.

Since a public health emergency was declared in British Columbia in 2016, over 13,000 people have died from drug overdoses. A 2020 analysis found that only about 2% of the B.C. opioid-related deaths were caused by prescription opioids alone. The other overdoses mainly involved illicit fentanyl and other street drugs.  

FDA Approves Genetic Test for Opioid Addiction Risk

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved a controversial genetic test that uses a patient’s DNA to assess whether they are at risk of developing opioid use disorder (OUD).  

Although the test is only intended for patients with short-term acute pain who have not used opioids before, there is concern about the test’s accuracy and whether it will be used “off-label” to assess addiction risk in chronic pain patients – who could potentially lose access to opioids as a result.

In approving the AvertD test, the FDA stipulated that it only be available by prescription to patients who consent to its use and have no prior history of using an oral opioid for pain relief.

The test is administered by a provider swabbing the cheek of a patient to collect a DNA sample, which will then be tested in a laboratory to see if the patient has 15 genetic markers that puts them at elevated risk of OUD.

According to the FDA, the test will help patients “make better informed decisions” about opioids, such as a patient facing surgery who wants to know what analgesic to use for acute post-operative pain.

AUTOGENOMICS IMAGE

"AvertD may help patients who are concerned about being treated with an opioid for acute pain,” Jeff Shuren, MD, director of the FDA's Center for Devices and Radiological Health, said in a statement. “The test is not intended to be used in patients being treated for chronic pain.”

But given the history of opioid guidelines being mistakenly applied to all kinds of patients, regardless of their condition, some worry the test will be misused.

“I’m sure it would be used for anyone who may be considered for opioid therapy,” says Lynn Webster, MD, a pain management expert and Senior Fellow at the Center for U.S. Policy. “I am all for gathering more data to help clinicians make better decisions, but we must exercise caution with such tests. Otherwise, the test may be over-read or misinterpreted. Some patients may be deprived of access to an opioid if they test positive or there can be a false sense of harmlessness from opioids if the test is negative. 

“I am most concerned that providers will see the results as binary. Either a patient will or won’t develop OUD, depending on the result. That would be a big mistake. Any such device or test must be used along with other clinical and personal information to help mitigate harm from using, or being denied, opioids.”

80% Accuracy

As part of its approval order, the FDA is requiring AutoGenomics – the company that makes AvertD – to provide training to healthcare providers on the proper use of the test and to conduct a post-market study of its performance and accuracy.

In 2022, an FDA advisory committee voted 11-2 against recommending an earlier version of AvertD, primarily because of concerns about false-negative and false-positive results. An observational study found the test was about 80% accurate in detecting genes associated with OUD.

"I believe 100% of the risk associated with this test is with false positives and false negatives -- both people being untreated or poorly treated because somehow it came back as a positive result, or being given inappropriate treatment because it said negative," said Timothy Ness, MD, an anesthesiologist and Professor Emeritus at the University of Alabama at Birmingham, an advisory panel member who voted no.

After the advisory committee vote, the FDA worked with AutoGenomics to modify the test and improve its accuracy. The company then submitted a premarket approval application for the modified test, which the FDA granted without going back to the advisory committee for further review.

“The FDA recognizes that in premarket decision-making for devices, there generally exists some uncertainty around benefits and risks. Given the totality of available evidence and the urgent need for medical devices that can make a positive impact on the overdose crisis, and specifically devices that can help assess the risk of developing OUD, the FDA determined that there is a reasonable assurance of AvertD's safety and effectiveness,” said Dr. Shuren.

But no test is foolproof in either its accuracy or implementation, as Dr. Webster learned when he developed a questionnaire that assesses addiction risk by asking patients about their family history and other potential risk factors. Webster was disappointed to learn his questionnaire was “weaponized” by some providers to deny opioid therapy to patients, particularly women with a history being sexually abused.

Webster says the risk of OUD can’t be measured by a genetic test alone.

“We should not think it is a diagnostic tool or a crystal ball. Having an increased risk due to genetics does not mean that, if exposed to an opioid, an individual necessarily will develop an opioid addiction,” Webster told PNN. 

“We have known for a long time that about fifty percent of the risk of developing an opioid addiction is due to genetics. The other fifty percent is due to environmental factors and life’s experience. Furthermore, people can develop OUD without genetic risks. OUD risk is dynamic, meaning it changes over time with adverse events in life and often co-morbid conditions. For example, there was a surge in all forms of drug abuse, including OUD, during the pandemic because of isolation and loneliness. This is not detected by a genetic test.”

Although the risk of a surgery patient misusing opioids or becoming addicted is low – less than one percent -- the parent company of AutoGenomics has a more stark assessment, calling surgery “a gateway to addiction” that puts another 7 million Americans at risk every year.

We Must Overcome Stigma Against Buprenorphine for Pain

By Dr. Stefan Franzen

For years I had a negative impression of buprenorphine as a pain medication, both from personal descriptions I had heard by pain patients and from the scientific and medical literature.

I have since learned that buprenorphine can be effective pain reliever. At a high dose, the efficacy is similar to that of high-dose morphine or oxycodone, which were once commonly used to treat chronic or intractable pain.

Today, high doses of any opioid are shunned by most doctors because they are subject to increased scrutiny by state medical boards or even investigation by the Drug Enforcement Administration. The medical and moral justification of alleviating patient suffering appears to be irrelevant to public health authorities, even when they profess to favor a humane policy to treat pain.  

We need a more rational discussion about opioids. Buprenorphine is an opioid that, when used alone, can play a role in pain treatment. Buprenorphine was developed in the United Kingdom in the 1960s and has been used in many countries to treat pain since the 1980s.

We must distinguish pure buprenorphine from Suboxone, which is a combination of buprenorphine and naloxone. Suboxone is given to people with opioid use disorder to help prevent abuse. If a tablet is crushed, extracted or injected by a drug abuser, the naloxone will block the effects of buprenorphine. However, if taken as directed under the tongue, the naloxone has much lower bioavailability.

A pain patient does not necessarily need naloxone and, depending on individual differences in body chemistry, the naloxone may even have negative effects. There is no reason to prescribe Suboxone for pain. It’s use as a pain medication is highly inappropriate, but may be the result of doctor’s fear of DEA action.

Pure buprenorphine is a different matter.

The CDC’s 2016 opioid guideline recommended that daily opioid doses not exceed 90 morphine milligram equivalents (MME).  Although voluntary, the guideline was seized upon by other federal agencies and state legislatures to justify draconian new laws and regulations that limited opioid doses to 90 MME or less.

No such limits have been set for buprenorphine. However, few doctors in the U.S. prescribe buprenorphine for pain, despite recent studies demonstrating its efficacy and international recognition that it is an effective analgesic.

For historical reasons, American doctors do not know much about buprenorphine as a pain medication. Moreover, many fear prescribing any opioid in today’s regulatory climate. Patients know that buprenorphine has been used to treat addiction and therefore are suspicious of it as a pain treatment. They are also justifiably concerned about being stigmatized as a drug abuser if they are prescribed Suboxone.

U.S. Opioid Policy Lacks Common Sense

In short, the stigma surrounding buprenorphine is a significant factor preventing development of a rational opioid policy in the U.S.

Many patients with experience taking morphine, oxycodone, hydrocodone and other opioids say they are safe and non-addictive. Research shows that is true for a great many pain patients. However, a small fraction of the population is susceptible to opioid abuse and addiction. This is a classic ethics problem.

Should we let 99% of patients suffer because 1% might harm themselves? How do other societies manage this problem? We know what doesn’t work. The “War on Drugs” has been an unmitigated disaster for everyone: drug abusers, doctors, pain patients and their loved ones. Our drug overdose rate is 15 times higher than that the of European Union.

Worse still, our medical system and corporate regulation appear to lack common sense guardrails needed to prevent the diversion of prescription opioids -- even after massive publicity, sensational books, documentaries, and popular miniseries on the opioid crisis.

In case anyone had any doubt, the book “American Cartel” shows that diversion was mainly practiced by large opioid distributors and a few manufacturers, who flooded vulnerable communities with prescription opioids. Theft and deception of doctors by drug abusers also contributed to diversion. Each of these could be controlled in a sensible way, without forbidding people in pain from receiving medication. Yet, at present it appears there is no political will in the U.S. to even treat pain, regardless of the suffering of millions.

Instead, the politicians and media blame opioid prescribing, which implicitly blames doctors and patients. Perhaps as a response to this seemingly hopeless situation, a growing number of medical researchers have begun testing pure buprenorphine for the treatment of pain.

After seeing the effectiveness of buprenorphine, which I discuss in my new book, “Z’s Odyssey,” I became convinced that it is a viable treatment for even severe, intractable pain. This should be a choice, but the problem today is that many patients do not have a choice.

Pure buprenorphine for pain was not available in the United States until 2010, when the low-dose Butrans skin patch became available.

In 2015, a buccal formulation designed for absorption through the cheek became available. Belbuca film is quite convenient and comes in a moderate dose.

For intractable pain, a sublingual formulation of buprenorphine known as Subutex can be prescribed off label for pain. Subutex is also used to treat opioid addiction, but does not contain naloxone.

A Subutex tablet placed under the tongue takes about 20 minutes to be completely absorbed. Because buprenorphine binds to the pain receptors more tightly than any other opioid, the dose in milligrams required for full effect is much lower than similar strength morphine. Many medical researchers have concluded that buprenorphine is an excellent analgesic, with low risk for addiction or overdose. If taken as directed, the risk of respiratory depression from buprenorphine is the lowest of any opioid.

For pain relief, U.S. doctors must prescribe Subutex off-label, which means that they are prescribing for a condition that is not FDA approved.  Subutex is approved for pain in Great Britain and most of Europe. The UK’s National Health Service recommends Subutex and other formulations of buprenorphine for patients “when weaker opioids for pain stop working.”

Of course, buprenorphine is not beneficial for every patient. And there is an issue of dental decay that requires careful monitoring and appropriate procedures. But for people in the most severe pain, who lack any other option because of the opioid prohibition mindset, buprenorphine may offer relief.

Finding a doctor willing to prescribe Subutex off label could be difficult. For severe or intractable pain that requires a high dose, a patient most likely needs to find a psychiatric or addiction treatment doctor licensed to prescribe buprenorphine in formulations such as Subutex that are pure buprenorphine.

Since 2000, the U.S. Congress has passed three laws that make buprenorphine more accessible to people with opioid use disorder.  If Congress can aggressively lower the barriers to prescribing high-dose buprenorphine for addiction treatment, then why shouldn’t pain patients have access to medication that has the same dose of the active agent?

There is an education gap that prevents doctors and society at large from effectively managing this situation. The medical literature is heavily weighted toward studies of buprenorphine for addiction, with almost 97% of studies on opioid use disorder and less than 3% on pain.  Pain patients also fear the stigma associated with buprenorphine as an addiction treatment, rather than an analgesic.

There is no objective reason for this. At the very least, buprenorphine should be an option for those forgotten patients who still live in pain. By overcoming the stigma of buprenorphine, doctors could treat patients with dignity by prescribing a safer and more effective medication. 

Stefan Franzen, PhD, is a Professor of Chemistry at North Carolina State University. Franzen is the author of “Patient Z” – a book that looks at pain, addiction and the opioid crisis through the eyes of a patient who can’t find good pain care. He recently published a sequel to Z’s story, called “Z’s Odyssey.”

Stimulants Involved in Growing Number of Fentanyl Overdoses

By Pat Anson, PNN Editor

The number of drug deaths involving both fentanyl and stimulants has soared in recent years, according to a new UCLA study that highlights the complex and changing nature of the U.S. overdose crisis.

Stimulants such as cocaine and methamphetamine are now involved in nearly a third of fentanyl-related overdoses, the most of any other drug class. Fentanyl is a synthetic opioid up to 100 times more potent than morphine and 50 times as potent as heroin.

In 2010, researchers say there were only 235 fatal overdoses in the U.S. involving illicit fentanyl and stimulants. In 2021, there were 34,429 drug deaths linked to fentanyl and stimulants, a 14,550% increase in a little over a decade.

"We're now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis," said lead author Joseph Friedman, PhD, an addiction researcher at the David Geffen School of Medicine at UCLA. "Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for health care providers.

“We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use."

People who overdose on stimulants and other non-opioid substances mixed with fentanyl may not be as responsive to naloxone, which only works as an antidote to opioids.

The study findings, published in the journal Addiction, highlight the four “waves” of the overdose crisis, which began with an increase in deaths from prescription opioids (Wave 1) in the early 2000s, followed by a rise in heroin deaths (Wave 2) in 2010, and fentanyl-related overdoses in 2013 (Wave 3). The fourth wave — overdoses from fentanyl and stimulants — began in 2015 and continues to escalate.

The Four Waves of Overdose Crisis

SOURCE: ADDICTION

Since cocaine, methamphetamine and other stimulants are not opioids, the findings undercut the long-held theory that the overdose crisis started with prescription opioids and is still being fueled by people addicted to them. Deaths involving prescription opioids and heroin have been in decline for several years.

Researchers found that fentanyl/stimulant deaths disproportionately affect African Americans and Native Americans. There are also geographical patterns to fentanyl/stimulant use. In the northeast US, fentanyl is usually combined with cocaine, while in the south and western US, fentanyl is most commonly found with methamphetamine.

"We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country," Friedman said.

In addition to its low cost, drug users say methamphetamine helps prolong fentanyl’s “high” and delays the onset of withdrawal symptoms.  

Counterfeit pills laced with fentanyl – which are frequently made to look like oxycodone or alprazolam (Xanax) – represent about a quarter of all illicit fentanyl seizures. Researchers say it is difficult to track deaths involving counterfeit pills because they are often mistaken for legitimate medication, so the data is not completely reliable.

In its most recent update on the overdose crisis, the CDC estimates there were a record 111,355 drug deaths in the 12-month period ending April 2023 -- about a thousand more deaths than the year before. Fentanyl and its analogues were involved in nearly 70% of the overdoses, stimulants were linked to about a third of them, and cocaine was involved in about a quarter of the drug deaths.

America’s Biggest Fear: Fentanyl and Opioid Addiction

By Pat Anson, PNN Editor

The fentanyl crisis is the biggest public health problem in the US, according to two new surveys that highlight Americans’ growing fears about opioid addiction and the toxicity of street drugs.

The first survey, conducted by Axios-Ipsos, found that opioids and fentanyl have surpassed Covid-19, firearms, obesity and cancer as the nation’s #1 public health threat. Over one in four Americans (26%) ranked opioids and fentanyl first, replacing gun violence as the top threat to public health.  

Top U.S. Public Health Threats

Fentanyl is a synthetic opioid that is 100 times more potent than morphine. It has been used safely for decades as an analgesic during surgery and to treat severe pain, but in recent years illicit versions of fentanyl have come to dominate the black market, where they are used in counterfeit medication or mixed with substances like heroin. Most fatal overdoses in the U.S. involve illicit fentanyl, not prescription opioids.

The Axios-Ipsos survey found that about four in ten adults (44%) are aware that U.S. overdose deaths reached a record high last year. Americans who live in rural areas, which have some of the highest overdose rates, are even more familiar (51%) with the rising number of drug deaths. 

Over half the respondents (51%) said they cared a lot about overdoses and think the government should be doing more to reduce drug deaths (79%). Most also believe that government does not make the health and well-being of citizens a priority (62%).  

While most Americans trust the health information they get from federal agencies like the CDC (64%) and FDA (62%), there is more trust placed in health information from personal doctors (89%) and family members/close friends (75%). 

Other key findings about respondents’ drug use in the last three months:

• 26% used a pain medication for which they had a prescription or knew someone who did

• 3% used a pain medication for which they did not have a prescription or knew someone who did

• 20% used cannabis or knew someone who did

• 2% used hallucinogenic drugs or new someone who did

• 2% used “other illegal drugs” or knew someone who did

“Pain medication” was not defined in the survey questions, so the responses may include some non-opioid analgesics.

The recently updated Axios-Ipsos American Health Index is based on a nationally representative sample of 1,162 adults, who were surveyed on a wide array of health topics from August 11-14.

Most Families Impacted by Addiction

The second survey, conducted by the non-profit KFF, asked a representative sample of 1,327 adults online and over the phone in July about a variety of drug and substance use issues.

Two-thirds of respondents said either they or a family member were addicted to alcohol or drugs, experienced homelessness due to addiction, or had a drug overdose resulting in hospitalization or death.  

Nearly three in ten (29%) said they or someone in their family were addicted to opioids, either prescription opioids or illicit ones like fentanyl and heroin. Opioid addiction was most common among rural residents (42%) and White adults (33%). Among those who experienced addiction firsthand, most said it had a negative impact on their family’s relationships and finances. 

Only 5% felt they themselves might be addicted to opioid painkillers, far less than those who believe they might be addicted to alcohol (13%). 

Fear about addiction is common. Over half (51%) of adults are worried that someone in their family will experience a substance use disorder and one-third (32%) are worried that someone in their family will overdose on opioids.  

About four in ten adults (39%) are worried that someone in their family will unintentionally consume illicit fentanyl, a fear that looms largest in rural areas (48%). 

SOURCE: KFF

Nearly three in ten respondents (29%) said they had been prescribed opioid pain medication in the past five years. Of those, most said their doctors had warned them about the risks of opioid addiction and dependence (57%), side effects from opioids (69%), other ways to manage pain (60%), and about keeping their medications in a safe place (58%).  

While fears about addiction to opioid pain medication are common, it doesn’t happen nearly as often as many people believe. A recent study in Australia found that 92% of patients prescribed opioids for the first time never progressed to long-term use. Less than 3% became persistent users or needed higher doses — and they were mostly seniors with chronic health problems.

Neither the KFF or Axios-Ipsos polls asked respondents about growing shortages of opioid pain medication or how the reduced supply was impacting legitimate pain patients.   

‘Unintended Victims’

The patient side of the story was shared this week in an opinion video by The New York Times. Video producers Vishakha Darbha, Lucy King and Adam Westbrook spoke with chronic pain patients who are the “unintended victims” of the national crackdown on opioid prescribing.

“America’s doctors have been put in a difficult position. But it doesn’t need to be this way. It is possible to stop overprescribing yet ensure that pain sufferers get the relief they deserve. The patients in our video have one message: Listen to us,” the producers said.

Large Study Debunks Myths About Rx Opioid Addiction

By Pat Anson, PNN Editor

A large new study in Australia is debunking myths about the addictive nature of opioid pain medication and how a single prescription can lead to long term use.

In an analysis of nearly 3.5 million Australians who were prescribed opioids for the first time, researchers found that 92% never progressed beyond low opioid use and only 3% became persistent users or needed higher doses. The “sustained use” of opioids occurred mostly in seniors (65 and older) suffering from cancer, depression, anxiety and other chronic health problems.

“Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period,” wrote lead author Natasa Gisev, PhD, a clinical pharmacist at National Drug and Alcohol Research Centre, UNSW Sydney.

“The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.”

Previous research estimated the risk of long-term opioid use as high as 57 percent, but Gisev and her colleagues say those studies are flawed because they excluded people with cancer and opioid use disorder, or used various definitions of long-term use. The Australian researchers took a different approach in tracking opioid prescriptions, developing five “trajectories of opioid use.”

The vast majority of patients had very low (75%) or low use (17%) of opioids. Others started with moderate opioid use and decreased to low use (3%), or began with low use and increased to moderate use (3%). Only 3% became sustained users or took higher doses.

Five-Year Trajectories of Opioid Use

JAMA NETWORK OPEN

“Overall, these findings suggest that most people who initiate an opioid prescription are likely to have low, time-limited exposure to opioids with little indication of ongoing use. This possibility is an important consideration for policymakers and stakeholders considering population-level prescribing of high-risk drugs,” researchers reported in JAMA Network Open.

“Opioids are essential drugs for acute and cancer pain, and many people with CNCP (chronic non-cancer pain) benefit from opioids. Continued focus and policy responses based on findings from a small group of people with increased risk of harms run the risk of limiting access to people who safely derive objective benefits from opioids.”  

That’s exactly what happened to millions of pain patients in the US, who lost access to opioids due to steep cuts in prescribing, chronic shortages of opioid medication, and a relentless drumbeat in the media about people becoming addicted or overdosing after one pill.  

“One prescription can be all it takes to lose everything,” the CDC said in a 2017 advertising campaign that emphasized the risks of prescription opioids, while ignoring the far more serious problem of illicit fentanyl and other street drugs.

Just how common is opioid addiction? Estimates are all over the map, ranging as low as 1% to as high as 40% for long-term opioid users.

“The problem with all of these studies is that they are retrospective in nature, limited to a particular patient population, and constrained by the diagnostic criteria in use at the time,” my late colleague Roger Chriss pointed out in a 2019 column on opioid addiction.  

Roger was prescient about the imprecision of diagnostic criteria. A little known 2021 study of U.S. veterans who were diagnosed with opioid use disorder (OUD) challenged how many actually had it. Researchers found that nearly 20% of veterans with OUD used prescription opioids without any signs of abuse and evidence was lacking in another 7% of cases. Less than 60% of the veterans had a “high likelihood” of being correctly diagnosed with OUD.

Should Suboxone Be Used to Treat Kratom Addiction?

By Pat Anson, PNN Editor

A man with a history of substance abuse – including addiction to kratom – has been successfully treated with buprenorphine/naloxone (Suboxone), according to a case study published in the journal Cureus.  Suboxone is a medication that is normally used to treat opioid use disorder.

Kratom is not derived from the opium poppy and is not an opioid. It’s an herbal supplement that comes from the leaves of a tree in southeast Asia, where it has been used for centuries as a stimulant and pain reliever. In recent years, millions of Americans have discovered kratom and use it to self-treat their pain, anxiety, depression and addiction.

The unidentified patient in the case study has a history of using cocaine, marijuana and alcohol, and suffers from anxiety and depression. He was introduced to kratom 12 years ago by his brother for stress relief and as a substitute for oxycodone. Over the years, the patient used more and more kratom, at one point spending up to $600 a week on kratom supplements.

After several failed attempts to wean himself off kratom, which resulted in severe withdrawal symptoms, the patient went to see his primary care physician, Dr. Paul Remick, one of the study’s co-authors. It was Remick who suggested that Suboxone might help him quit kratom.

“He’d been struggling with depression, anxiety, all these various issues. He was pretty reluctant to try therapy like Alcoholics Anonymous or trying to speak to a therapist,” explained lead author Martin Arhin, a medical student at the University of North Carolina at Chapel Hill. “Dr. Remick suggested Suboxone, since kratom has some like opioid-like properties. He felt like it could potentially work. And fortunately, it did.”

After 23 weeks of using Suboxone, the patient’s withdrawal symptoms subsided and he stopped using kratom. He’s also been successfully tapered off Suboxone, a drug that many people wind up taking for life.   

Suboxone is only approved for opioid use disorder and there is no clinical evidence that it can treat kratom addiction. Such a use, while legal, would be considered “off-label” by the FDA. But based on this one anecdotal case, Arhin and his co-authors say Suboxone could be a treatment for kratom dependence.

“Currently, there is no established evidence-based consensus for the treatment of kratom addiction and withdrawal, leaving individual providers to decide on the appropriate course of action,” they wrote. “We recognized the patient's dependency on kratom and subsequently implemented a treatment plan utilizing buprenorphine/naloxone, which effectively alleviated withdrawal symptoms and supported the patient's abstinence from kratom. We suggest that this drug combination may be a potential treatment for kratom addiction.”

‘Kratom Saved My Life’

Ironically, many people use kratom as an alternative to Suboxone. In a 2016 PNN survey of over 6,100 kratom users, nearly ten percent said they used kratom primarily as a treatment for opioid addiction. Most said it was very effective (91%) in easing their withdrawal symptoms and worked better than Suboxone, with fewer side effects.

“Kratom saved my life. I tried every other type of treatment for drug addiction over the past 10 years. Subutex, methadone, total abstinence and the 12 step program. Each time I failed. After 2 years of Suboxone, I stopped treatment and began using kratom,” one respondent told us.

“Because of kratom, I no longer have to worry about heroin (or methadone or Suboxone) making me sick. I've been clean for 2 years. I can hold a job now, and I only use it when I need pain relief or need to relax,” another respondent wrote.

“I became hooked on oxycodone and had to take Suboxone to get off it. The problem is Suboxone withdrawals were nearly as bad, so I used kratom to cure that,” another patient said.

“Kratom truly saved my life. I've always suffered from extreme anxiety, but it has decreased drastically since taking it. Withdrawals from opiates and Suboxone are awful. I would not have been able to get clean without kratom. I'm confident in saying that if you make kratom illegal, the number of overdoses will rise,” wrote another kratom user.

The DEA and FDA have tried to make kratom illegal by having it declared a Schedule I controlled substance. So far, those efforts have failed due to a public backlash.

Kratom is sold legally in most U.S. states, but a handful of states and cities have banned it over concerns about addiction and overdoses.  About 100 deaths nationwide have been linked to kratom use, but in the vast majority of cases other drugs and illicit substances were involved.

About two million Americans use kratom, primarily to treat chronic pain. A 2020 study funded by the National Institute on Drug Abuse concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and has a low risk of adverse effects.

Although many people use kratom to self-treat opioid addiction and ease withdrawal symptoms, the FDA won’t allow kratom vendors to advertise or promote kratom for addiction treatment or any other medical purpose. This month, the FDA sent a warning letter to the Sunshine Trading Company in Colorado, warning it to stop promoting its kratom products for “opiate withdrawal.”

“You market kratom products for the treatment or cure of opioid addiction and withdrawal symptoms. However, these products have not been determined by FDA to be safe and effective for these (or any other) uses. Further, the unproven treatments could cause patients to forego or delay FDA-approved treatments for opioid addiction or withdrawal,” the FDA said.

In recent years, several other kratom vendors have received similar warning letters from the agency..

Studying Natural Opioids Could Lead to New Non-Addictive Analgesics

By Dr. John Streicher, University of Arizona

Opioid drugs such as morphine and fentanyl are like the two-faced Roman god Janus: The kindly face delivers pain relief to millions of sufferers, while the grim face drives an opioid abuse and overdose crisis that claimed nearly 70,000 lives in the U.S. in 2020 alone.

Scientists like me who study pain and opioids have been seeking a way to separate these two seemingly inseparable faces of opioids. Researchers are trying to design drugs that deliver effective pain relief without the risk of side effects, including addiction and overdose.

One possible path to achieving that goal lies in understanding the molecular pathways opioids use to carry out their effects in your body.

What Are Natural Opioids?

The opioid system in your body is a set of neurotransmitters your brain naturally produces that enable communication between neurons and activate protein receptors. These neurotransmitters include small protein-like molecules like enkephalins and endorphins. These molecules regulate a tremendous number of functions in your body, including pain, pleasure, memory, the movements of your digestive system, and more.

Opioid neurotransmitters activate receptors that are located in a lot of places in your body, including pain centers in your spinal cord and brain, reward and pleasure centers in your brain, and throughout the neurons in your gut. Normally, opioid neurotransmitters are released in only small quantities in these exact locations, so your body can use this system in a balanced way to regulate itself.

The problem comes when you take an opioid drug like morphine or fentanyl, especially at high doses, for a long time. These drugs travel through the bloodstream and can activate every opioid receptor in your body. You’ll get pain relief through the pain centers in your spinal cord and brain. But you’ll also get a euphoric high when those drugs hit your brain’s reward and pleasure centers, and that could lead to addiction with repeated use. When the drug hits your gut, you may develop constipation, along with other common opioid side effects.

Targeting Opioid Signals

How can scientists design opioid drugs that won’t cause side effects?

One approach my research team and I take is to understand how cells respond when they receive a message from an opioid neurotransmitter. Neuroscientists call this process opioid receptor signal transduction. Just as neurotransmitters are a communication network within your brain, each neuron also has a communication network that connects receptors to proteins within the neuron.

When these connections are made, they trigger specific effects like pain relief. So, after a natural opioid neurotransmitter or a synthetic opioid drug activates an opioid receptor, it activates proteins within the cell that carry out the effects of the neurotransmitter or the drug.

Opioid signal transduction is complex, and scientists are just starting to figure out how it works. However, one thing is clear: Not every protein involved in this process does the same thing. Some are more important for pain relief, while some are more important for side effects like respiratory depression or the decrease in breathing rate that makes overdoses fatal.

So what if we target the “good” signals like pain relief and avoid the “bad” signals that lead to addiction and death? Researchers are tackling this idea in different ways. In fact, in 2020, the U.S. Food and Drug Administration approved the first opioid drug based on this idea, oliceridine, as a painkiller with fewer respiratory side effects.

However, relying on just one drug has downsides. That drug might not work well for all people or for all types of pain. It could also have other side effects that show up only later on. Plenty of options are needed to treat all patients in need.

Inhibiting a Protein Relieves Pain

My research team is targeting a protein called Heat shock protein 90, or Hsp90, which has many functions inside each cell. Hsp90 has been a hot target in the cancer field for years, with researchers developing Hsp90 inhibitors as a treatment for many cancer types.

We’ve found that Hsp90 is also really important in regulating opioid signal transduction. Blocking Hsp90 in the brain blocked opioid pain relief. However, blocking Hsp90 in the spinal cord increased opioid pain relief. Our recently published work uncovered more details on exactly how inhibiting Hsp90 leads to increased pain relief in the spinal cord.

Our work shows that manipulating opioid signaling through Hsp90 offers a path forward to improve opioid drugs. Taking an Hsp90 inhibitor that targets the spinal cord along with an opioid drug could improve the pain relief the opioid provides while decreasing its side effects. With improved pain relief, you can take fewer opioids and reduce your risk of addiction. We are currently developing a new generation of Hsp90 inhibitors that could help realize this goal.

There may be many paths to developing an improved opioid drug without the burdensome side effects of current drugs like morphine and fentanyl. Separating the kindly and grim faces of the opioid Janus could help provide the pain relief we need without addiction and overdose. 

John Streicher, PhD, is an Associate Professor in the Department of Pharmacology at the University of Arizona. Dr. Streicher has published over 70 peer-reviewed articles and is engaged in numerous drug discovery campaigns to create new analgesics. He receives funding from the National Institutes of Health, the Arizona Biomedical Research Commission, the Flinn Foundation, and the University of Arizona.

This article originally appeared in The Conversation and is republished with permission.

DEA Lifts Limits on Buprenorphine Use

By Pat Anson, PNN Editor

After years of strict limits on the number of patients that a provider can treat with buprenorphine, it’s suddenly a lot easier to prescribe the drug for opioid use disorder (OUD). The Drug Enforcement Administration has eliminated the “X-Waiver” program for buprenorphine, a move required by Congress under the 2023 Appropriations Act.  

Elimination of the X-Waiver removes all patient caps and significantly increases the number of providers that can treat OUD with buprenorphine, a long-acting opioid similar to methadone. When combined with naloxone, an overdose prevention drug, buprenorphine reduces opioid cravings and eases withdrawal. Prescriptions for Suboxone and other buprenorphine/naloxone combinations now only require a provider to get a standard DEA registration for controlled substances.

“DEA fully supports this significant policy reform. ln this moment, when the United States is suffering tens of thousands of opioid-related drug poisoning deaths every year, the DEA 's top priority is doing everything in our power to save lives. Medication for opioid use disorder helps those who are fighting to overcome opioid use disorder by sustaining recovery and preventing overdoses,” DEA Administrator Anne Milgram wrote in a January 12 letter to providers.

The DEA is also developing a new mandatory eight-hour training program for providers to help them identify and treat OUD when they apply for or renew their registrations. The new training will be required on June 21.

“I think this is overdue. Buprenorphine can reduce the risks of overdose by 60% and is much safer than methadone,” says Lynn Webster, MD, an expert in pain management who is a Senior Fellow at the Center for U.S. Policy. “It would be controversial, but I believe low-dose buprenorphine should be OTC as a harm reduction measure. At least there should be a discussion about the potential benefit vs risk.”

Pressure to Prescribe

It remains to be seen how the elimination of the X-Waiver will affect pain patients. Over the years, we’ve heard complaints from patients who say they were coerced by their doctors into taking Suboxone, even though it’s not approved as a treatment for pain. With patient caps removed and more doctors able to prescribe buprenorphine, there could be added pressure on pain patients to take Suboxone – whether they show signs of OUD or not.

“I understand the pressure to use buprenorphine for pain rather than traditional opioids. It is a much safer opioid than most, so it should be considered as a first line therapy,” says Webster. “However, that is the rub. It is not effective or tolerated in many patients.  Patients have a legitimate concern that they may be coerced to transition to buprenorphine when their existing medications are working and there are no signs of abuse.     

“I don't think the change in regulations will mean more doctors will push their patients to use buprenorphine, because the mind-set is already there.” 

A little-known aspect of buprenorphine is that it blocks other opioids from working – meaning anyone who is taking it should be aware that if they have acute pain from an accident, trauma or surgery, they’ll have to rely on non-opioid pain relievers.  

While often touted as the most effective medication for OUD, most people who take buprenorphine relapse and starting taking opioids again. About two-thirds of the patients who receive Suboxone stop filling prescriptions for it after just three months. 

Although it’s difficult to get high on buprenorphine, it can still be misused. A 2021 study found the misuse rate for buprenorphine was over two times higher than misuse rates for hydrocodone, oxycodone and other opioid pain medications.

Charges Against Founder of Genetic Testing Company Dropped

By Pat Anson, PNN Editor

The U.S. Department of Justice has quietly dropped criminal charges against the founder and CEO of Proove Biosciences, a genetic testing company based in California that was accused of paying physicians over $3.5 million in illegal kickbacks. A judge dismissed the case against Brian Meshkin and five other defendants last month “in the interests of justice” after federal prosecutors declined to move forward with the case.

“There has been so much injustice over the past 6 years that it is wonderful to see truth prevail.  I am excited to have the opportunity to set the record straight and to move forward from here with my head held high,” Meshkin said in a statement.

A spokesperson for the U.S. Attorney’s Office in San Diego declined to comment on the case being dismissed, according to The Orange County Register.

Proove specialized in genetic testing of pain patients and claimed its DNA tests could determine how well they metabolized opioid medication and if they were at risk of abuse. The company claimed that 94% of patients experienced significant pain relief within 60 days of treatment changes based on their test results.

Proove’s aggressive marketing included millions of dollars in “research fees” paid to physicians who ordered its tests, a practice that ran afoul of federal kickback laws. In 2017, the company’s headquarters in Irvine, CA was raided by FBI agents and Proove was placed into a court-ordered receivership – a form of bankruptcy – when its business collapsed.

The former vice-president of marketing for Proove plead guilty in 2020 to paying illegal kickbacks. The following year, the National Spine & Pain Center in Maryland agreed to pay $5.1 million in restitution to Medicare as part of a criminal settlement for taking kickbacks from Proove.

Meshkin blamed the company's legal and financial problems on “erroneous and damaging” reports by STAT News, which detailed how physicians could make up to $144,000 a year if they funneled their patients’ genetic tests to Proove.

“This work was destroyed by misinformation spread by a handful of disgruntled ex-employees and contractors, spread by the media, and blindly adopted by some in the Southern District of California office of the U.S. Attorney and the FBI,” Meshkin said. 

“That misinformation and false and defamatory allegations directed at Proove hurt thousands of people beyond the company itself, including the many patients and their families who have died from or whose lives were impacted by opioid overdoses and suicide that could have been prevented with access to Proove’s life-saving technology.”

Many questions remain about the effectiveness of the tests. A genetic expert told STAT News the company’s testing claims were “hogwash” and said they exploited fears about opioid addiction.  A Montana pain patient who took the test and followed Proove’s treatment advice said they didn’t work for her.

“To me it was a waste of time and money. The meds it said I should be taking either didn’t work, stopped working, or made me sick. And the meds I should not be taking, I do just fine on,” she told PNN in 2017.

There Is Another Drug Reform Bill the Senate Must Pass

By Michael C. Barnes, Guest Columnist

After last month’s midterm elections, the U.S. Senate passed the Medical Marijuana and Cannabidiol Expansion Research Act. The House had passed the bill in April, and President Biden signed it into law on December 2. The new law has been described as “modest” because it mostly facilitates research on marijuana and cannabidiol to support the development of medications for approval by the Food and Drug Administration (FDA).

The law also eliminates a longstanding regulatory roadblock that has prevented marijuana research; hindered the development of marijuana-derived, FDA-approved medications; and led to 37 state-regulated markets for marijuana products that do not meet federal consistency, purity, and potency standards. New research can be expected to yield marijuana-derived medications that the FDA can approve.

There is another regulatory burden that the Senate must eliminate before the end of this year. This change in federal law would also be modest, but it would facilitate access to treatment for opioid use disorder (OUD), which is essential amid the nationwide fentanyl poisoning crisis. S. 3257 would expand the time health care providers can hold long-acting, injectable buprenorphine (an FDA-approved medication for OUD) from 14 days to 60 days. It’s that simple. But like the new marijuana research law, the modest change will make a significant difference.

In the 12 months that ended June 30, 2022, 102,842 people died of a drug poisoning. Of those, 69,150 involved synthetic opioids, predominantly illegal fentanyl. Facilitating access to evidence-based treatment for OUD is more important now than ever. Changing the law cannot wait until the next Congress gets up and running.

S.3257 would amend the Controlled Substances Act, which currently requires that a health care provider administer injectable buprenorphine OUD medication to the patient named on the prescription within 14 days after the medication was delivered to the provider. The supposed purpose of the 14-day limit is to prevent the diversion of the medication to the illicit market.

But in 2020, the Government Accountability Office (GAO) reported that “all of the provider groups GAO spoke with said that diversion of injectable … buprenorphine is unlikely, and representatives from three of the six provider groups said that the design of these formulations reduce opportunities for diversion due to how they are administered.”

For patients and providers, the 14-day limit is too short considering the coordination required to facilitate injectable buprenorphine prescribing, insurance coverage and payment, delivery and receipt, and appointment scheduling and attendance. Sixty days are necessary to ensure that medication administration may take place at a time when the patient, provider, and medication are available.

Additionally, the 14-day limit wastes valuable health care resources and places patients’ recovery and lives at risk. For example, if an insured patient is not able to attend a medical appointment on or before the 14th day after the injectable buprenorphine was delivered to his or her provider, the medication must be disposed of.

It is unlikely that an insurer would pay for a replacement product, and it is common for patients not to be able to pay for medications out of pocket. As a result, a patient may be forced to go without a week or months’ worth of medication for OUD. This situation can put the patient at risk for a recurrence of OUD symptoms, active substance use, poisoning by illicit substance, and death.

In June, the House of Representatives passed H.R. 7666 with broad bipartisan support. Section 264 of H.R. 7666 contains a provision expanding the 14-day limit to 60 days.

In passing the marijuana research act, the Senate proved itself willing and capable of enacting modest yet meaningful drug reforms during its lame-duck session. To prevent drug poisonings and avoid wasting lifesaving medications, the Senate must do so again by expanding the 14-day limit to 60 days.

Michael C. Barnes is the managing attorney for Sequel Health Law. He serves as counsel to Aimed Alliance, a not-for-profit health policy organization.

The goal of Aimed Alliance is to create a society in which consumers can make informed and individually appropriate decisions about their health care, without those decisions being overridden by third parties.

Stopping Rx Opioid Therapy Raises Risk of Overdose

By Pat Anson, PNN Editor

Discontinuing opioid therapy for people with chronic pain raises the risk of a patient dying from an overdose, according to a new Canadian study that calls for better guidance for healthcare providers on the risks associated with abrupt tapering.

Researchers analyzed the medical histories of over 14,000 pain patients in British Columbia who were on long term opioid therapy from 2014 to 2018 – a period when physicians in Canada and the United States were being urged to restrict opioid prescriptions due to a worsening overdose crisis. The vast majority of patients studied were either tapered to a lower dose or their opioid treatment was discontinued, regardless of whether they showed signs of opioid use disorder (OUD).  

The study findings, published in PLOS Medicine, show that discontinuing opioid therapy for pain was associated with increased overdose risk. The association was even stronger for the small minority of patients diagnosed with OUD. In total, 530 people in the study (3.8%) experienced either a fatal or non-fatal overdose, with 120 of them dying.

“Our findings underscore the need for healthcare providers and policymakers to carefully consider potential unintended adverse effects of discontinuing opioid treatment for chronic pain when developing prescribing interventions and making practice decisions,” wrote lead author Mary Clare Kennedy, PhD, a Research Scientist with the BC Centre on Substance Use and a Research Fellow at the University of British Columbia.

“Given the harms of opioid treatment discontinuation identified in this and past studies, non-consensual and abrupt discontinuation of opioid treatment for pain is contraindicated in almost all instances.”

Kennedy and her colleagues were unable to determine what substances were involved in the overdoses, but they believe some patients who had their opioid therapy stopped may have resorted to illicit fentanyl and other street drugs to manage their pain, withdrawal and other symptoms. Over 73% of the overdose deaths that occurred in British Columbia during the study period involved fentanyl.

Previous studies have also found that opioid tapering raises the risk of an overdose and mental health crisis. A study published last year in JAMA found that tapered patients were 68% more likely to be treated for opioid withdrawal, drug overdose or alcohol intoxication, and they were twice as likely to experience depression, anxiety or a suicide attempt.

The FDA warned in 2019 that rapid tapering or abrupt discontinuation of opioids could result in serious harm to patients, including withdrawal, uncontrolled pain, psychological distress and suicide.

‘Reckless Mistreatment of Patients’

Despite this growing body of evidence, forced tapering and opioid discontinuation continues – some of it caused by the heavy-handed tactics of law enforcement. Over 200 pain patients were recently cut off from opioids after their California doctor had his DEA license suspended without warning. One patient and his wife died by suicide within a week of the DEA’s action.

“Not only are we collectively causing harm, we are failing to stop causing harm even when we agree that we're causing it, which is actually worse,” says Stefan Kertesz, MD, an associate professor at the University of Alabama at Birmingham, who is leading a study of pain patient suicides.

Kertesz says regulators, insurers, journalists and law enforcement have misinterpreted overdose studies to suggest that opioid prescribing, particularly at higher doses, was the root cause of the overdose crisis.  

“Many clinicians and policymakers engaged in aggressive extrapolation that went far beyond the data. Many journalists and legal plaintiffs described the prescriptions in a way that aggravated matters. They made dose into a fetish, a performance metric, and a threshold for law enforcement,” Kertesz told PNN. “Dose based quality metrics, payor standards and legal investigation thresholds incentivize reckless mistreatment of patients.

“My ultimate question is when will agencies like the National Committee for Quality Assurance, the Office of Inspector General, and law enforcement actually come to appreciate the evidence in play?”

It took six years, but the CDC recently revised its 2016 opioid guideline to include specific language warning of the dangers of tapering or discontinuing opioids.

“Clinicians should avoid abrupt discontinuation of opioids, especially for patients receiving high dosages of opioids, should avoid dismissing patients from care, and should ensure appropriate care for patients with pain and patients with complications from opioid use,” the revised guideline states.

Opioid Prescriptions Down Sharply for Medicare Patients

By Pat Anson, PNN Editor

The number of Medicare beneficiaries receiving opioid prescriptions has declined significantly since 2016, according to a new government report that also found steep declines in the number of beneficiaries receiving high doses or who appear to be doctor shopping.

The report by the Department of Health and Human Service’s Office of Inspector General found that over 21 million people -- 23% of Medicare Part D beneficiaries -- received at least one opioid prescription in 2021, down from 33% of beneficiaries in 2016. Over 51 million people are currently enrolled in Part D.

The Centers for Medicare and Medicaid Services (CMS) adopted new safety rules in 2018 that discourage high dose prescribing and limit the initial supply of opioids to 7 days. The rules also allowed pharmacists and insurers to flag Medicare patients deemed to be at high risk, as well as their prescribers.

The rules appear to have had a major impact on prescribing. In 2016, over half a million Medicare beneficiaries received a daily opioid dose of at least 120 MED (morphine milligram equivalent). By 2021, that fell to less than 200,000 patients, a 60 percent decrease in high dose prescribing.   

MEDICARE PATIENTS RECEIVING HIGH DOSE OPIOIDS

HHS Office of Inspector General

Since 2016, the number of Medicare beneficiaries who appeared to be doctor shopping dropped from 22,300 to 1,800; while the number of doctors with “questionable” prescribing patterns fell from 401 to just 98.  Patients were flagged for doctor shopping if they were on high doses and received opioids from four or more prescribers or four or more pharmacists.

“The opioid epidemic continues to grip the nation. There is clearly still cause for concern and vigilance, even as some positive trends emerge,” the OIG report found. “The number of Medicare Part D beneficiaries who received opioids in 2021 decreased to approximately a quarter of a million beneficiaries, extending a downward trend from prior years. Further, fewer Part D beneficiaries were identified as receiving high amounts of opioids or at serious risk of misuse or overdose. The number of prescribers ordering opioids for large numbers of beneficiaries at serious risk was steady.”

But there is little evidence that less prescribing is reducing addiction and overdoses.  The Centers for Disease Control and Prevention estimates there were nearly 81,000 opioid-related deaths in 2021, nearly twice the number reported in 2016, when the CDC’s opioid guideline was released. The vast majority of deaths involved illicit fentanyl and other street drugs, not prescription opioids.

The OIG report found that 50,391 Part D beneficiaries experienced an opioid overdose (either fatal or non-fatal) in 2021, but did not break down how many were linked to illicit or prescription opioids.

Over one million Medicare beneficiaries were diagnosed with opioid use disorder (OUD) last year, but only one in five received a medication like Suboxone or methadone to treat their condition. Medicare patients were far more likely to receive naloxone, an overdose reversal drug. Over 445,000 beneficiaries received a prescription for naloxone, an 18% increase from 2020.