A Case Study in the Undertreatment of Surgical Pain

By Dr. Stefan Franzen

“Patient Z” is a close family member who has an incurable form of arthritis known as ankylosing spondylitis. His back is partially fused and his large joints are so damaged that they all need replacement. Each step he takes, even with a walker using his arms as the main support, is exceedingly painful. Just getting into a car to go to a doctor’s office is excruciating.

Several years ago, Patient Z went through an opioid rotation from morphine/oxycodone to buprenorphine. This was a forced choice. His pain clinic told him that they would make a final push to taper him to a daily dose of 120 MME (morphine milligram equivalents). That was the statewide cap on prescribing. Patient Z had reduced gradually for years to accommodate them, but when the dose fell below 180 MME, he felt miserable much of the time.

Patient Z transferred to a pain institute where he was prescribed pure buprenorphine for pain. The doctors at the institute had conducted clinical studies and found buprenorphine to be as effective as morphine. When Patient Z reached the maximum daily dose of buprenorphine in sublingual form, he felt relief.

Patient Z might never have chosen buprenorphine, but he found that it managed his pain on most days. In his experience, the dose was as effective as 200 MME of morphine and oxycodone. But pain flares can overwhelm even that dose.

A surgeon urged surgery because stenosis and deformation of the neck caused by ankylosing spondylitis could lead to paralysis. Realizing that he was losing sensation in his arms and hands, Patient Z scheduled the surgery.

At the pre-op, he was told that the surgery required an incision in the front and back of his neck. The surgeon would implant a metal brace that was about 5 cm long. Patient Z asked the surgeon’s nurse about pain management and she assured him that he would be comfortable in the hospital.

He also asked his pain clinic what they would do to help with post-operative pain. They told him to rely on hospital care. Patient Z knew the constraints on the pain clinic and did not push the point. When he arrived for surgery, he still did not know what was planned for post-surgical pain control.

‘My Pain Level is 10’

The surgery was successful. Patient Z woke up in a hospital bed with a neck brace. But he could not move. After a few hours the pain set in. He could not believe that pain could be so all-consuming. Even lying motionless in bed, his body throbbed with pain radiating out from the back of his neck. He felt like he was nailed to the bed.

The nurses were told not to give him buprenorphine on the first night. One nurse said he was afraid that Patient Z would suffer respiratory depression. At first, they only gave him acetaminophen and pregabalin.

In the middle of the night, Patient Z called the nurse and said something he never thought he would say: “My pain level is 10.”

The nurse left to contact the doctor in charge. An hour passed. It seemed like an eternity to Patient Z, who was in agony. Finally, the nurse returned with a muscle relaxant and a two-milligram hydromorphone pill. That is the equivalent of 8-10 milligrams of oral morphine.

Patient Z knew how low this dose was, but he swallowed the pill and hoped the pain would stop. It did not. Patient Z is stoic and had suffered from extreme pain in the past, but he had to speak up. The pain was truly unbearable. His collapsed hips were throbbing. Pain was shooting down his arms and legs. Any movement brought on involuntary spasms.

Finally, at 5 am, a nurse gave Patient Z a two-milligram injection of hydromorphone. The pain abated and he could finally rest. This dynamic of denial and waiting until Patient Z was nauseous from pain before providing relief continued for three more days. Nurses rotated in and out, and the doctors made decisions that left him miserable most of the time.

On the fourth day after surgery, Patient Z was released from the hospital. Patient Z asked what he should do to control the pain. The surgeon looked unhappy. He said that the pain of surgery should pass within a week and Patient Z had already received ample pain medication. Other pain was not the surgeon’s concern, and he was told to consult with his pain physician.

By this time, one of the nurses who had seen Patient Z several times came to understand how debilitating his pain was. The nurse told Patient Z that she had observed many recovering surgery patients. She said that neck operations with an incision from the back is one of the most painful.

Patient Z was lucky that people could see his struggle with pain. Many patients have pain that is not recognized. Even so, the nurse told him that they could not write a prescription for opioid pain medication. Someone must have decided that Patient Z really did have unmet pain needs.

Maybe the nurse advocated for him because, as Patient Z was being released the nurse unexpectedly gave him a vial of pain medication. She said that it would be enough to keep him comfortable until the neck pain subsided. When Patient Z arrived home and looked at the vial, he saw that the oral hydromorphone dose was 12 milligrams daily, the equivalent of approximately 50 MME. And he only had a six-day supply.

This was not nearly enough to give Patient Z relief from the neck pain, back pain, hip pain and systemic inflammatory pain. To make matters worse, the instructions stated that he should not take buprenorphine for the six days he was on hydromorphone.

After one day, Patient Z’s misery escalated because he was going through withdrawal while also recovering from neck surgery. After two days, Patient Z resumed taking buprenorphine and stopped taking hydromorphone. At least the buprenorphine gave him partial relief.

Few patients take buprenorphine for pain in the U.S. It has been reported that hydromorphone is compatible with buprenorphine in post-surgical pain management.  Yet doctors and nurses appeared unfamiliar with buprenorphine, which is also used to treat opioid addiction when combined with naloxone. Their comments in the hospital showed that they did not understand that buprenorphine is safer than other opioids and can also be used to treat pain.

The combination of misunderstanding buprenorphine and the current practice of giving as little pain medication as possible put a severely ill patient through an unnecessary ordeal. Today, most medical education and pain research is solely aimed at reducing or eliminating opioids, rather than using buprenorphine and other alternative opioids to provide at least some relief.

Buprenorphine is slow-acting and therefore not the ideal medication for acute pain. But studies have shown that it can be combined with other opioids to provide relief. For some types of pain, there is no substitute for opioid pain medication.

Stefan Franzen, PhD, is a Professor of Chemistry at North Carolina State University.

He is the author of “Patient Z” – a book that looks at pain, addiction and the opioid crisis through the eyes of a loved one who can’t find good pain care.

Franzen recently published a sequel to Z’s story and his use of buprenorphine for pain, called “Z’s Odyssey.”

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.”

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..

Restoring Safe Supply of Rx Opioids Would Reduce Overdoses

By Pat Anson, PNN Editor

A decade long effort to reduce the supply of opioid pain medication in the U.S. has contributed to a surge in overdose deaths and made the illicit drug supply more toxic, according to a new study.

“A big reason that we have such a problem with addiction in this country is because people can't access legitimate pain medication,” said lead author Grant Victor, PhD, an assistant professor at Rutgers University School of Social Work. “Our findings support a change in policy.”

Victor and his colleagues analyzed toxicology data from nearly 2,700 accidental overdose deaths in the Indianapolis metropolitan area (Marion County, Indiana) from 2016 to 2021, comparing them to patient records in the state’s prescription drug monitoring program (PDMP).

Their findings, published in the Journal of Substance Use and Addiction Treatment, show that less than half the people who overdosed (43.3%) had any kind of PDMP record, meaning they were never prescribed an opioid pain reliever or buprenorphine (Suboxone), a medication used to treat opioid use disorder.

Most of the decedents who did have a prescription for an opioid analgesic or buprenorphine had not filled one in the 30 days prior to their deaths, indicating that prescription opioids are not driving overdose deaths in Marion County. Overdoses there increasingly involve illicit fentanyl, a synthetic opioid 100 times more potent than morphine, which accounts for nearly 90% of the county’s overdoses.  

There were 637 drug deaths in Marion County in 2021, nearly twice the number that died in 2016. During that period, opioid prescriptions in the county fell by nearly a third.

MARION COUNTY PUBLIC HEALTH DEPT.

Toxic Drug Market

Victor says many of the overdose deaths could have been prevented if a safer supply of prescription opioids was still accessible – both to legitimate patients and those who misuse the drugs.

“There was a wave of policy initiatives that effectively tamped down on the diversion of prescription opioids, but did so primarily by increasing surveillance of prescribing practices for opioids. And through a number of mechanisms, that made it more difficult for individuals with legitimate pain concerns to access these types of medications,” Victor told PNN.

“When you remove a certain class of drugs that is federally regulated and can be monitored and dosed appropriately, it leaves folks with few options. Options that are currently available are illicit and the potency of these drugs is highly variable. The drug market in general, as we know it today, is very toxic and that is one of the main drivers in the overdose crisis.”

Victor says some of his own family members have chronic pain and after years of taking opioids safely, they’ve been cutoff and told to take Tylenol. He said it’s rare for a pain patient to die from an overdose and few meet the diagnostic criteria for substance use disorder.   

“There are a number of researchers who are trying to drive this point home and hope to reverse some of the policy initiatives that have unfolded over the last few years that have been perhaps unintentionally harmful to public health and to chronic pain patients,” he said.

“We've been swept up in this kind of frenzy about prescription opioids. They're still making movies about the Sackler’s (owners of Purdue Pharma). My opinion of them is not all that high, but I think it is a convenient kind of scapegoat to portray pharmaceutical companies as the evil here, when they’re not a primary concern. When you're looking at public health and what's currently driving overdose deaths, it’s not prescription opioids.”

Few previous studies have compared overdose deaths directly to prescription drug data, which would seem to be an obvious way to get to the bottom of what’s causing the overdose crisis.  One such study looked at opioid overdoses in Massachusetts, finding that only 1.3% of those who died had an active prescription for opioids.

New VA Guideline: Opioids Should Not Be Used for Chronic Pain

By Pat Anson, PNN Editor

The U.S. Department of Defense (DoD) and Department of Veterans Affairs (VA) have doubled down on a guideline first released in 2017 that strongly recommends against the use of opioids for chronic pain.

In an updated clinical practice guideline, the agencies continue to recommend that opioids not be used to manage chronic non-cancer pain, especially in younger patients, and that long-acting opioids not be used to treat patients with short-term, acute pain.

The VA/DoD guideline will potentially affect millions of service members, veterans and their families. Nearly 1.5 million Americans serve in the armed forces and over 800,000 in the National Guard and Reserves. The Veterans Administration provides health services to another 6 million veterans and their families.

The updated guideline was quietly released in May 2022, but is only drawing attention now in a mostly favorable review published in the Annals of Internal Medicine.

“Compared with the 2017 recommendation against initiation of long-term opioid therapy, the updated recommendation against opioid therapy in general for chronic pain is broader and reflects the evidence that opioid therapy for any duration may be harmful,” wrote lead author James Sall, PhD, Director of VA’s Office of Evidence-Based Practice.

“Ultimately, despite finding some evidence for a small improvement in musculoskeletal and noncancer neuropathic pain, the guideline development group maintained that the potential for catastrophic harms of opioids and serious adverse events, especially with long-term use, outweighed any potential benefits of temporarily improved pain severity and functional status in patients with chronic pain.”

‘Potentially Transformative’ for U.S. Healthcare

The updated opioid guideline has 20 recommendations, nine of which are based on weak or inconclusive evidence. Unlike the recently revised CDC opioid guideline, there were no public hearings or opportunities for the public to comment or provide input. There is also no discussion of dose thresholds or morphine milligram equivalents (MME), suggesting the authors believe that any dose of opioids is potentially risky.

Three new recommendations in the new VA/DoD guideline involve opioid tapering, mental health evaluations, and the use of buprenorphine to treat pain.

The guideline urges doctors to consider using buprenorphine instead of full agonist opioids for patients needing opioids daily for chronic pain. Although the quality of the evidence for this recommendation was deemed “insufficient,” the VA/DoD believe buprenorphine as a partial agonist has less risk for overdose and misuse, and is less likely to cause euphoria.

Buprenorphine is a Schedule III opioid that is FDA approved for pain when used alone. Buprenorphine is also used to treat opioid use disorder when combined with naloxone in drugs like Suboxone. The DEA recently eliminated the “X-Waiver” program for buprenorphine, which is likely to significantly increase the number of doctors that prescribe it and the number of patients that receive it.

An editorial published in the Annals of Internal Medicine called the recommendation that buprenorphine be used for pain “potentially transformative” and "likely to expand into the greater U.S. healthcare system."

"The updated VA/DoD guideline is both conservative and radical," wrote co-authors Chinazo Cunningham, MD, and Joanna Starrels, MD, both from Albert Einstein College of Medicine. "Although the VA/DoD guideline recommends that buprenorphine be prescribed for chronic pain if daily opioids are prescribed, the recommendation itself is likely to change decision-making about whether opioids should be prescribed."

Although several recent studies have found that opioid tapering significantly raises the risk of an overdose, withdrawal or mental health crisis, the VA/DoD guideline found there is “insufficient evidence to recommend for or against any specific tapering strategies.” It only recommends that doctors and patients “collaborate” on reducing opioid doses and that tapering not be forced.

“The potential benefits of opioid tapering outweighed the potential harms of opioid withdrawal,” the guideline claims.

Before opioids are prescribed for either acute or chronic pain, the guideline recommends that the mental health of patients be evaluated for depression, anxiety, psychotic disorders and suicide. Although some patients may resent being screened for mental health problems, the guideline says “it is better for providers to know about underlying behavioral health comorbidities than to initiate long-term opioids without this clinical knowledge.”

The revised guideline reaffirms previous recommendations that benzodiazepines not be co-prescribed with opioids and that patients on long-term opioid therapy be regularly screened with urine drug tests “to decrease the risk of self-directed violence.”

Opioid prescribing to veterans, family members and those on active duty has declined significantly in recent years, as it has for the rest of the population. The revised VA/DoD guideline notes – without a hint of irony – that reduced prescribing has led to an increased use of illicit opioids by veterans and higher overdose rates.

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.

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.

OHSU Focused on Opioid Tapering, but at What Cost to Patients?

By Pat Anson, PNN Editor

An internal medicine clinic at Oregon Health & Science University has significantly reduced the use of opioid pain medication through the use of a review board that oversees whether prescriptions are in line with federal and state guidelines, according to a new study.

“The question was, how do clinics actually implement those guidelines in practice?” co-author Jonathan Robbins, MD, assistant professor of medicine at the OHSU School of Medicine, said in a press release. “The opioid review board was a way to turn high-level recommendations into action steps we can take in our clinic to treat patients and create a culture of safe prescribing.”

The study highlights the declining use of high dose opioids at the clinic since 2017, along with increased prescriptions for the addiction treatment drug Suboxone (buprenorphine). But critics say the research failed to address whether pain relief and quality of life improved for patients or if they suffered side effects when they were tapered to lower doses or prescribed buprenorphine.

“This is a frustratingly vague account of a practice that could have serious implications for treating a large number of people with chronic pain,” said Bob Twillman, PhD, former Executive Director of the Academy of Integrative Pain Management. 

“The summary statistics presented give us some idea about how frequently people are being tapered, and how often they are being transitioned to buprenorphine, but we really could use some better data analysis, especially with respect to outcomes,” Twillman wrote in an email. “The article continues a trend in the literature, in which an output of these interventions (i.e., the change in prescribing) is confused with an outcome (i.e., what happens to the patient as a result). Basically, the article says, ‘We decided to do this, and we think it's great.’ But there are no data presented to back that up.”

“We’ll let the article stand for itself,” is the response PNN received from Erik Robinson, a senior communications specialist at OHSU. Robinson declined a request to speak with the authors of the study and to identify members of the review board.

“The article published in the Annals of Family Medicine describes a clinical practice in general terms, and we will not engage questions about specific patient outcomes and clinical discussions among physicians,” Robinson said in an email.

‘High-Risk Cases’ Reviewed

What can be gleaned from the article is that patients with more than 6 opioid prescriptions in a 9-month period had their cases reviewed, along with those on high daily doses that exceed 90 MME (morphine milligram equivalent) or those co-prescribed benzodiazepines. The 90 MME threshold is based on a recommendation in the 2016 CDC opioid guideline.

“We combed through 14,000 patients in our clinic and developed a registry about who we’re chronically treating with opioids,” co-author Mary Pickett, MD, associate professor of medicine in the OHSU School of Medicine, said in the press release. “We picked out high-risk cases to review and invited those patients’ primary care doctors to consult with us.”

The review board initially identified 664 patients on chronic opioid therapy (COT). Three years later, there were only 458 COT patients at the clinic, the number of high-dose opioid prescriptions was reduced significantly, and buprenorphine prescriptions increased over 300 percent.  

But there is no information on how many patients experienced withdrawal, whether their pain levels and quality of life improved, or if patients were satisfied with their treatment. The study only notes that “a subset of patients have had adverse response to tapering.” Those cases were reviewed a second time, but again there are no details about patient outcomes or if the tapering was stopped..

The FDA warned in 2019 that rapid tapering or abrupt discontinuation of opioid therapy could result in serious harm to patients, including withdrawal, uncontrolled pain, psychological distress and suicide. A recent study found that tapered patients were 68% more likely to be hospitalized for withdrawal, overdose or alcohol intoxication, and twice as likely to have a mental health crisis such as depression, anxiety or suicide attempt.  

“We’re coaching primary care providers to approach this carefully, and, when necessary, slowly taper their patients,” Robbins says in the OHSU press release. “We don’t do anything abruptly, and patients have supported this careful process.”

But Twillman wonders if the tapering was voluntary and if patients agreed to have their cases reviewed. The press release mentions a waiver being signed by patients, but the study does not.

“That detail is missing from the scientific publication, and it raises a concern about the extent to which that signature is truly voluntary, or if it is coerced by a threat to stop prescribing if the waiver is not signed. What is the consequence for patients who don't sign the waiver?” asked Twillman.

“And what happens if tapering or transition to buprenorphine is recommended, and the patient doesn't agree? We've seen the dangers of involuntary tapers in several studies now, so is any tapering that happens truly voluntary, and supported appropriately with ancillary services? In sum, this article raises more questions than it answers.”

Patient Urged to Taper

“In my experience, they care more about de-prescribing than they do about their patients' individual needs,” says Emma, a patient at OHSU’s Comprehensive Pain Center who lives with an intractable pain condition. She asked that we not use her real name because she fears retaliation or being discharged from the pain clinic.

Emma gets opioids from her primary care provider, but can’t get any from the pain clinic, which she says has a strict policy against prescribing opioids at any dose.

Emma says she is constantly urged to taper by her OHSU doctor. The pain clinic emphasizes non-opioid alternative treatments such as physical therapy, acupuncture, yoga, massage and psychotherapy. 

“I’m getting pretty damn fed up with OHSU’s total lack of concern for my wellbeing. They’ve all but eliminated individualized care when it comes to the treatment of pain.”

— OHSU patient

“I told them that I had spent years trying every possible alternative, and had become suicidal due to severe untreated pain. That was when my primary doc asked me to at least consider opioids as an alternative to taking my own life. I did try them, and they gave me my functionality back,” she told PNN.

“I'm getting pretty damn fed up with OHSU's total lack of concern for my wellbeing. They've all but eliminated individualized care when it comes to the treatment of pain. And how they can label the Comprehensive Pain Center a ‘pain management clinic’ while completely eliminating an entire class of effective medications is beyond me.”

Roger Chou’s Role

Patients at OHSU’s Comprehensive Pain Center were apparently not included in the study on tapering. But they too have their cases regularly reviewed by a panel of pain management experts.

One of the experts is Roger Chou, MD, a prolific researcher and longtime critic of opioid prescribing who heads OHSU’s Pacific Northwest Evidence-based Practice Center (EPC). According to the website GovTribe, over the last five years OHSU has been awarded over $2 billion in federal grants – much of it going to the EPC to support Chou’s medical research.

In addition to his research, Chou co-authored the CDC’s 2016 opioid guideline and has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group.

In 2019, Chou co-authored an op/ed with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.” He also served on a state task force that supported a rigid opioid tapering policy for Medicaid patients in Oregon.

Emma considers Chou “a major player behind all of OHSU’s anti-opioid policies” and is concerned that guidelines that he helped write are being used to justify tapering.

“It’s concerning to me that they’re justifying these actions by stating that they’re ‘in alignment with the guidelines.’ So essentially, they are both creating and enforcing their own set of guidelines with no transparency and no real oversight,” she said.

Last year, the American Medical Association called for a major overhaul of the CDC guideline, saying it was clear the agency’s recommendations “harmed many patients” by setting arbitrary limits on opioids.

The CDC is currently in the process of revising and possibly expanding the guideline, with the goal of releasing a new version next year. One of the authors drafting the revised guideline is Roger Chou.

Fearing DEA, Many Pharmacies Stop Dispensing Addiction Medication

By Aneri Pattani, Kaiser Health News

When Martin Njoku saw opioid addiction devastate his West Virginia community, he felt compelled to help. This was the place he’d called home for three decades, where he’d raised his two girls and turned his dream of owning a pharmacy into reality.

In 2016, after flooding displaced people in nearby counties, Njoku began dispensing buprenorphine to them and to local customers at his Oak Hill Hometown Pharmacy in Fayette County.

Buprenorphine, a controlled substance sold under the brand names Subutex and Suboxone, is a medication to treat opioid use disorder. Research shows it halves the risk of overdose and doubles people’s chances of entering long-term recovery.

“I thought I was doing what was righteous for people who have illness,” Njoku said.

But a few years later, the Drug Enforcement Administration raided Njoku’s pharmacy and accused the facility of contributing to the opioid epidemic rather than curbing it. The agency revoked the pharmacy’s registration to dispense controlled substances, claiming it posed an “imminent danger to public health and safety.” Although two judges separately ruled in Njoku’s favor, the DEA’s actions effectively shuttered his business.

“I lost everything that I worked for,” Njoku said.

Lawyers, pharmacists, harm-reduction advocates and a former DEA employee say Njoku’s case is emblematic of the DEA’s aggressive stance on buprenorphine. An opioid itself, the medication can be misused, so the DEA works to limit its diversion to the streets. But many say the agency’s policies are exacerbating the opioid epidemic by scaring pharmacies away from dispensing this medication when it’s desperately needed.

Drug overdose deaths hit record highs last year, and despite medical experts considering medications like buprenorphine the gold standard, less than 20% of people with opioid use disorder typically receive them. The federal government has taken steps to increase the number of clinicians who prescribe buprenorphine, but many patients struggle to get those prescriptions filled. A recent study found that 1 in 5 U.S. pharmacies do not provide buprenorphine.

“Pharmacies are terrified they’re going to lose their DEA registration and go out of business,” said Charles “Buck” Selby, a former inspector and chief compliance officer for the West Virginia Board of Pharmacy, who retired in 2018.

The ramifications can be particularly acute in rural areas, where a dearth of addiction treatment providers, lack of transportation and stigma against these medications already create barriers. If pharmacies decline to provide buprenorphine too, patients will have few options left, Selby said.

The DEA did not respond to requests for comment.

Buprenorphine Misuse

Like many other prescription drugs, buprenorphine can be found illegally on the street. There are unscrupulous doctors who hand out prescriptions and pharmacists who fill them. Subutex, which consists of buprenorphine alone, is easier to misuse and typically has higher street value than Suboxone, a combination of buprenorphine and the overdose-reversal drug naloxone.

In the case against Njoku’s pharmacy, an assistant U.S. attorney explained that the DEA “got slapped hard for being asleep at the switch as the opioid crisis ramped up. … They’re trying to make sure that Subutex doesn’t become the next problem,” according to court transcripts.

But recent research suggests that buprenorphine misuse has decreased in recent years even as prescribing has increased, and that most people who use diverted buprenorphine do so to avoid withdrawal symptoms and because they can’t get a prescription.

Misuse rates for buprenorphine are twice as high as misuse rates for hydrocodone, oxycodone and other opioid medications, but buprenorphine is less likely to cause overdoses because its effects taper off at higher doses, said Dr. Aaron Wohl, medical director of the Florida-based coalition Project Opioid.

In Njoku’s case, the DEA said in court documents that several “red flags” had suggested the pharmacy’s actions were irresponsible. First, many of the prescriptions it filled were for Subutex instead of Suboxone. Patients also traveled – sometimes out of state – to get prescriptions, drove long distances within West Virginia to reach Njoku’s pharmacy, and often paid in cash.

In traditional prescription drug cases, these are all markers of trouble. But — as Njoku’s lawyers argued and two judges later agreed — they can also reflect the difficulty of getting addiction treatment, which is sometimes more challenging than obtaining illicit drugs.

“The practical reality and context of West Virginia turn these additional flags from red to yellow,” U.S. District Judge Joseph Goodwin wrote in his opinion. Patients may go out of their way for the drug because there aren’t enough nearby doctors who prescribe it or pharmacies that stock it, he wrote. They might pay cash because they’re uninsured or Medicaid won’t cover prescriptions written by an out-of-network doctor. And they might prefer Subutex because it’s often cheaper than Suboxone.

By 2020, Goodwin and an administrative law judge at the DEA had both ruled in Njoku’s favor. But several insurers and drug suppliers had already stopped doing business with him. Njoku closed the pharmacy in April 2021. 

‘Prescribing Cliff’

Across the country, when a pharmacy stops providing buprenorphine, the ripple effects can be far-reaching.

Trish Mashburn works at two independent pharmacies in western North Carolina. When a nearby pharmacy stopped dispensing buprenorphine, she began getting five calls a day from prospective customers trying to get their prescriptions filled, she said. Although both her employers stock buprenorphine, they order only a set amount, so Mashburn often must turn patients away.

Research in North Carolina and Kentucky has found that many pharmacists worry that ordering more buprenorphine will trigger a DEA investigation. The DEA does not specify thresholds for controlled substances, but it requires wholesalers to flag suspicious orders. In turn, wholesalers limit how much a pharmacy can buy or create algorithms to detect orders that exceed projected need.

They base these limits, in part, on the DEA’s enforcement actions, said Larry Cote, a former DEA attorney who now advises wholesalers, pharmacies and other clients on regulatory compliance. Since pharmacies are not typically privy to how these limits are set, many simply order small batches of buprenorphine out of caution.

That creates a “prescribing cliff,” said Bayla Ostrach, lead author of a paper studying this issue in North Carolina. Doctors may prescribe buprenorphine to more patients, but pharmacies order enough for only a certain number of customers. Since many people stay on buprenorphine for years, once the pharmacy hits its self-established quota, it may rarely have openings for new patients.

A Lee County, Florida, man thought he was one of the lucky ones. James, 34, had been filling his Subutex prescription at the supermarket chain Publix for seven years. In that time, he held steady jobs and cared for his wife and children. (James asked KHN to withhold his last name so future employers wouldn’t judge him on his addiction history.)

Then, last year, James said, he went to get his prescription refilled and was told Publix no longer stocks Subutex — the medication the DEA considered a “red flag” in Njoku’s case. Publix did not respond to requests for comment.

A decade ago, when James began the medication, he chose Subutex because it was cheaper than Suboxone. Today, most insurance plans cover Suboxone, and the price difference has narrowed somewhat.

James was not eager to change to a potentially pricier medication. And he worried a different drug might disrupt his recovery — a common sentiment among patients in long-term recovery, said Dr. Nathan Mullins, director of addiction medicine fellowship at Mountain Area Health Education Center in North Carolina. Changing their medication is unnecessary and can cause needless anxiety, Mullins said.

Luckily, James found an independent pharmacy that provides Subutex. It’s more expensive, since the new place doesn’t accept his insurance, he said. He pays about $40 a week, compared with $40 a month previously.

But James said it’s worth it.

“I’ve been in 10 rehabs and a million detoxes, and the only thing that has worked for me was one sublingual tablet,” James said. Along with therapy, “this saved my life.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

The Rx Opioid Most Likely To Be Misused May Surprise You

By Pat Anson, PNN Editor

For well over a decade, addiction treatment providers and public health officials have been touting the benefits of buprenorphine, an opioid that can treat both pain and addiction. When combined with naloxone in drugs like Suboxone that treat opioid use disorder (OUD), buprenorphine reduces cravings for opioids and lowers the risk of abuse.    

But a new study published in JAMA Network Open suggests that someone is far more likely to misuse buprenorphine than other opioids. In fact, the misuse rate for buprenorphine is over two times higher than misuse rates for hydrocodone, oxycodone and other opioid pain medications.

Researchers at the National Institute on Drug Abuse and the Centers for Disease Control and Prevention conducted the study, looking at data from nearly 215,000 people who participated in the National Surveys on Drug Use and Health from 2015 to 2019.

Respondents were asked if they misused prescription opioids “in any way that a doctor did not direct you to use them.” If they used someone else’s prescription or took opioids in greater amounts or more often than they were told by a doctor, that was considered “misuse.”

Researchers crunched the numbers and found that the vast majority of people do not misuse opioid pain medication and take it as directed. Oxycodone, for example, was misused by 12.7% of respondents who took it, followed by hydromorphone (11.8%), hydrocodone (11.6%), and prescription fentanyl (11.5%). Tramadol (7.8%) was misused the least.  

Addiction treatment drugs were misused the most. Buprenorphine was misused by 29.2% of the people who took it, followed by methadone at 22.2 percent. It’s not uncommon for someone getting OUD treatment to have relapses, so perhaps that finding is not altogether surprising.

% MISUSE RATES FOR PRESCRIPTION OPIOIDS

SOURCE: JAMA NETWORK OPEN

Although buprenorphine is misused at a rate over two times higher than other opioids, researchers chose to focus on the positive: a recent downward trend in buprenorphine misuse, despite increases in the number of patients receiving buprenorphine treatment.

“In 2019, nearly three-fourths of US adults reporting past-year buprenorphine use did not misuse their prescribed buprenorphine, and most who misused reported using prescription opioids without having their own prescriptions. These findings underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse,” researchers concluded.

What Is Misuse?

Every study has its flaws, and this one is no exception. Findings based on self-reported survey results are subject to poor memories, recall bias and concerns about stigma. The researchers’ broad definition of “misuse” could also result in a diagnosis of OUD when none actually exists, according to a pain management expert.

“It is not really clear what any of the data means clinically because of the very broad definition of the word misuse,” said Lynn Webster, MD, Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript. “Behavior of taking an extra pill to control pain, despite it not being specifically directed by the prescribing provider, could be described as ‘misuse.’ This is not necessarily harmful, even if it is inappropriate. The implication is that simply taking an additional pill is an indication of OUD behavior. That would not be an appropriate characterization of the behavior. 

“In fact, the authors report the most common reason to misuse medication is to relieve pain in the OUD and non-OUD groups. This may imply that most people who are misusing their medications are experiencing undertreated pain.” 

The JAMA study is not the first to report a high rate of buprenorphine misuse. The DEA’s 2020 National Drug Threat Assessment reported that buprenorphine is misused more often than methadone or hydrocodone, and that it was poised to replace oxycodone as the most commonly misused prescription opioid. Unlike the JAMA study, the DEA said the misuse of buprenorphine was increasing, not declining.   

Some Pharmacies Won’t Sell Suboxone, But Street Dealers Do

By Nina Feldman, WHYY

Louis Morano knew what he needed, and he knew where to get it.

He made his way to a mobile medical clinic parked on a corner of Philadelphia’s Kensington neighborhood, in the geographical heart of the city’s overdose crisis. People call it “the bupe bus.”

Buprenorphine is a drug that curbs cravings and treats the symptoms of withdrawal from opioid addiction. One of the common brand name drugs that contains it, Suboxone, blends buprenorphine with naloxone. Combined with cognitive behavioral therapy, it is one of the three FDA-approved medicines considered the gold standard for opioid-addiction treatment.

Morano had tried Suboxone before — he had purchased some from a street dealer and had used it to get through his workday, when he couldn’t use heroin. It kept the misery of withdrawal sickness at bay.

Morano, 29, has done seven stints in rehab for opioid addiction in the past 15 years. So he had a sense of how the drug would make him feel. He’d always sort of thought of it as a crutch. But after a slip following his latest stint in rehab, he said, he committed to recovery.

“I can’t do this anymore, and I need something,” Morano said.

The bupe bus — a project of Prevention Point Philadelphia, the city’s only syringe exchange program — is part of Philadelphia’s efforts to expand access to this particular form of medication-assisted treatment, known as MAT, for opioid addiction.

Morano was first in line at the mobile clinic. When the doors of the bus heaved open, Dr. Ben Cocchiaro waved Morano inside, where they squeezed into a tiny exam room.

Cocchiaro and Morano discussed how buprenorphine might help Morano’s recovery succeed this time, and whether he’d be open to seeing a therapist. Cocchiaro gave Morano instructions on how to take the medication, and then called a pharmacy to authorize a prescription.

Barriers to Treatment

To date, much of the research on barriers to buprenorphine access has focused on the fact that too few medical providers are certified to write the prescriptions. According to federal law, doctors must apply for a special waiver from the Substance Abuse and Mental Health Services Administration, or SAMHSA, to prescribe buprenorphine. To get the waiver, a doctor must undergo eight hours of training — and can prescribe the drug to a maximum of 30 patients at a time, to start. Given these constraints, many doctors don’t bother.

But pharmacists are also a part of the problem. Because they fill the prescriptions, pharmacists are the gatekeepers for the drug, and not all of them are willing to take on that role. Increasing pharmacists’ involvement in distributing buprenorphine might be just as important as persuading more doctors to prescribe it, according to Dan Ventricelli of the Philadelphia College of Pharmacy.

“We can write a bunch of prescriptions for people,” he said. “But if they don’t have a pharmacy and a pharmacist that’s willing to fill that medication for them, fill it consistently and have an open conversation with that patient throughout that treatment process, then we may end up with a bottleneck at the community pharmacy.”

Just a few blocks from the bupe bus in Kensington, Richard Ost owns an independent pharmacy. He said his store was one of the first in the neighborhood to stock buprenorphine. But after a while, Ost started noticing that people were not using the medication as directed — they were selling it instead.

Buprenorphine acts as a partial opioid agonist, which means it’s a low-grade opioid. When taken in pill or tablet form, it’s unlikely to cause the same feelings of euphoria as heroin would, but it might if it were dissolved and injected. Many people buy it on the street for the same reason Morano did: to keep from going into withdrawal between injecting heroin or fentanyl. Others buy it to try to quit using on their own.

“We started seeing people do it in our store in front of us,” said Ost. He said it’s unethical to dispense a prescription if a patient turns around and sells it illegally, rather than use it. “Once we saw that with a patient, we terminated them as a patient.”

Ost explained that the illegal market for Suboxone also meant customers trying to stay sober were being continually targeted and tempted.

“So if we were having a lot of people in recovery coming out of our stores, the people who were dealing illicit drugs knew that, and they would be there to talk to them and they would say, ‘Well, I’ll give you this’ or ‘I’ll give you that,’ or ‘I’ll buy your Suboxone’ or ‘I’ll trade you for this.’”

Ost said that eventually his staff didn’t feel safe, and that neither did the customers. He understands the value of bupe but said it just wasn’t worth it. He mostly has stopped carrying it.

Even those pharmacies that aim to stock buprenorphine can run into problems. Limits set by wholesalers require pharmacies to order the drug in small, frequent batches. Though pharmacies can apply for exemptions to order more at a time, or to have a higher percentage of their total stock consist of controlled substances, doing so invites a higher level of scrutiny from the wholesaler and, in turn, the Drug Enforcement Administration.

Another issue is that doctors and pharmacists receive different education about how long buprenorphine should be prescribed before tapering a patient off it. Many medical providers might prescribe the drug for long-term treatment, based on recent SAMHSA guidelines, while pharmacists may view longer courses of treatment as posing the risk of long-term dependency.

“It’s not even that they’re on different pages,” said Ventricelli of the College of Pharmacy. “It’s that they’re reading completely different books.”

If a patient going through withdrawal can’t get buprenorphine quickly, the stakes are high. Silvana Mazzella, associate executive director at Prevention Point, said that when it’s not available, patients are more likely to turn back to heroin or fentanyl.

“We’re in a situation where if you are in withdrawal, you’re sick, you need to get well, you want help today, and if you can’t get it through medication-assisted treatment, unfortunately you will find it a block away, very quickly, and very cheaply,” she said.

Doctors with Prevention Point have found a pharmacy near the bupe bus that will reliably dispense buprenorphine to their Philadelphia patients. It’s a neighborhood branch of a local chain, called the Pharmacy of America.

The head pharmacist, Anthony Shirley, said he’s comfortable filling the scripts because he trusts that the doctors at Prevention Point will write prescriptions only for patients who need the medication. He has heard firsthand from patients who say buprenorphine saved their lives.

“That’s something you can’t really put a price tag on,” Shirley said. For him, the calculation is simple: His store is in an area where many people need buprenorphine. That means it’s his job to get it to them.

This story is part of a partnership that includes WHYY, NPR and Kaiser Health News. KHN 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.

FDA: Pain Patients Dependent On Opioids Are Not Addicted

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has released new guidance to drug makers to streamline the development of buprenorphine products to treat opioid addiction. Commonly known by the brand name Suboxone, buprenorphine has long dominated the market for addiction treatment.

Of importance to pain patients is a statement about the guideline by FDA commissioner Scott Gottlieb, MD, that seeks to clarify the difference between opioid addiction and patients who need opioids for pain relief.

Gootlieb said there is still stigma and misunderstanding – even in the medical and addiction fields – about the difference between opioid addiction and dependence.

“Because of the biology of the human body, everyone who uses a meaningful dose of opioids for a modest length of time develops a physical dependence. This means that there are withdrawal symptoms after the use stops,” Gottlieb said. “A physical dependence to an opioid drug is very different than being addicted to such a medication.

“Addiction requires the continued use of opioids despite harmful consequences on someone’s life. Addiction involves a psychological preoccupation to obtain and use opioids above and beyond a physical dependence. But someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

“Someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

— Dr. Scott Gottlieb, FDA Commissioner

In recent years new and generic formulations of buprenorphine have been released in tablets, sublingual films, injections and implants, and the FDA is trying to promote the development of more of them.

The guidance released by the agency basically tells drug makers they may be able to submit new drug applications for buprenorphine products without conducting the safety and efficacy trials that are usually required for other medications.

“The guidance we’re finalizing today is one of the many steps we’re taking to help advance the development of new treatments for opioid use disorder, and promote novel formulations or delivery mechanisms of existing drugs to better tailor available medicines to individuals’ needs,” Gottlieb said. “Our goal is to advance the development of new and better ways of treating opioid use disorder to help more Americans access successful treatments.”

There are currently only three drugs approved by the FDA for medication-assisted treatment (MAT) – buprenorphine, methadone and naltrexone. Physicians wishing to prescribe buprenorphine to patients must have a special certification from the DEA and are limited in the number of patients they can treat.

Buprenorphine is an opioid that is also used to treat pain. When combined with naloxone, buprenorphine reduces cravings for opioids and lowers the risk of abuse.

Some addicts have discovered that buprenorphine can also be used to get high or to ease their withdrawal pain from heroin and other opioids. Buprenorphine is such a popular street drug that the National Forensic Laboratory Information System ranked buprenorphine as the third most diverted opioid medication in the U.S. in 2014. 

Opioid Painkillers Top Selling Drug in 10 States

By Pat Anson, Editor

If you live in Oklahoma, the drug you’re most likely to be prescribed is the opioid painkiller Vicodin -- or some other combination of hydrocodone and acetaminophen.

In Texas, the #1 drug is Synthroid (levothyroxine) – which is used to treat thyroid deficiencies.

In California, its Lipitor (atorvastatin) – a statin used to treat high cholesterol.

And Tennessee has the unique distinction of being the only state in the country where the addiction treatment drug Suboxone (buprenorphine/naloxone) is the most prescribed drug.

These findings are part of an interesting study by GoodRx, an online discount drug company, on prescribing trends in all 50 states. GoodRx looked at pharmacy and insurance data from around the country – not just its own customers -- from March 2017 to February 2018.

It then developed a map to show how prescription trends can vary by region and by state.

Levothyroxine (Synthroid) is easily the top selling drug in the country. It’s #1 in 26 states (AR, AZ, CO, CT, FL, IA, KS, KY, LA, ME, MI, MN, MT, ND, NJ, NV, OR, PA, SD, TX, UT, VT, WA, WI, WV, WY).

Hydrocodone (Vicodin, Norco, Lortab) is #1 in 10 states (AK, AL, GA, ID, IL, IN, MS, NC, NE, OK), mainly in the South and Midwest. As recently as 2012, hydrocodone was the most widely prescribed medication in the country. Since then, hydrocodone prescriptions have fallen by over a third and it now ranks 4th nationwide.

Atorvastatin (Lipitor) is #1 in 5 states (CA, HI, MD, MO, VA) and so is lisinopril (MA, NH, NM, OH, RI), a medication used to treat high blood pressure.

There are a few outliers. New York, for example, is the only state that’s #1 in amlodipine (Norvasc), a blood pressure medication, and Delaware and South Carolina are the only states where the leading prescription drug is Adderall, a medication used to treat Attention Deficit Hyperactivity Disorder (ADHD).   

That brings us to Tennessee, one of the states hardest hit by the opioid crisis. In 2012, doctors wrote 1.4 opioid prescriptions for every citizen in Tennessee, the second highest rate in the country. The state then moved aggressively to shutdown pill mills and expand access to addiction treatment -- which explains why Tennessee is #1 for Suboxone.

Prescriptions for opioid pain medication have dropped by 12% in Tennessee since their peak, but overdose deaths and opioid-related hospitalizations continue to climb, due largely to heroin and illicit fentanyl.  No other state even comes close to Tennessee in per capita prescriptions for Suboxone.  Addiction treatment has become such a growth industry that Tennessee has adopted measures to rein in the overprescribing of Suboxone.

What Makes Buprenorphine Risky for Pain Patients

By Jane Babin, Guest Columnist

Buprenorphine is the darling of the addiction treatment industry, rapidly replacing methadone as the "medication assisted treatment" of choice for opioid use disorder (OUD) and addiction.  

Unlike methadone, which can only be dispensed through an opioid treatment program, buprenorphine can be prescribed in the privacy of a physician's office and filled at a pharmacy.  As a class III controlled substance, prescriptions for buprenorphine can be phoned or faxed in, and scripts can be refilled up to 5 times in 6 months without a new prescription.

Class II controlled substances, like hydrocodone, oxycodone and morphine, require a new prescription each month and can neither be refilled nor phoned in.

The only federal limitations on prescribing buprenorphine for OUD is that a physician must complete mandatory education and treat only a limited number of patients (currently 275). 

Ironically, these restrictions do not apply when buprenorphine is prescribed off-label for pain, leading some physicians and patients to turn to buprenorphine for chronic pain as class II opioids become increasingly harder to get.

Yet without training on buprenorphine’s unique pharmacology and its implications, physicians treating chronic pain may be unaware of the risks it presents. Let me explain why.

Buprenorphine’s Effect on Other Opioids

Buprenorphine is an opioid that acts as an agonist of the mu opioid receptor (MOR), which causes pain relief, just like class II opioids.  It also has side effects similar to other opioids, including tolerance, dependence, abuse potential, constipation, sedation and potentially fatal respiratory depression. 

What distinguishes buprenorphine from other opioids is that it is only a partial MOR agonist (50%).  Thus the effects of buprenorphine -- both pain relief and the undesirable side effects – don’t exceed half that of other, full agonist opioids.

Buprenorphine also has a ceiling of maximum effectiveness that reaches a plateau as the dosage is increased. That ceiling is well below what can be obtained with morphine and other opioids, but the side effects can still lead to death in opioid-naïve patients.  Buprenorphine has a long plasma half life, binds very strongly to MOR, and remains bound for extended periods of time.  Its usefulness in treating OUD is believed to lie in these properties, because it activates MOR sufficiently to curb drug craving, but not enough to elicit the euphoric effects that can lead to addiction. 

When an opioid that has higher analgesic potency, but lower MOR affinity, such as morphine or heroin, is also administered, buprenorphine wins the battle to bind and remains bound to MOR.  It can displace both heroin and naloxone from MOR, but neither can displace buprenorphine.  Naloxone can be effective when co-administered with buprenorphine -- as it is in combination drugs such as Suboxone -- but not after the administration of buprenorphine. 

Buprenorphine is also a kappa opioid receptor antagonist, which is thought to further reduce euphoria and addictive reinforcement. That’s great for patients with OUD, because it helps them resist the temptation to abuse opioids, and dampens or eliminates the euphoric effect of heroin or other opioids should they relapse.  

Increasingly, buprenorphine is being advocated for chronic pain patients.  With no more "proof" of efficacy for treating chronic pain than any other opioid, it has emerged as a less objectionable opioid because it appears safer in the eyes of addiction treatment specialists, such as Dr. Andrew Kolodny, who object to full MOR agonists for chronic pain. 

Yet safety is in the eyes of the beholder.  Despite its decreased abuse potential, buprenorphine can still be abused and cause overdoses because the ceiling effect for respiratory depression does not apply universally, particularly to opioid-naïve patients and children. Buprenorphine has caused the death of at least one child from unintentional exposure. 

Buprenorphine should not be used as the first opioid prescribed for chronic pain.  Because it cannot achieve the full analgesic effects that other opioids can, there is significant risk of buprenorphine leaving pain undertreated or even untreated.  A chronic pain patient on long-term buprenorphine therapy who experiences acute or breakthrough pain may not be able to get relief by taking another opioid.  Even more disturbing is the lack of pain control in patients who need surgery, have an acute injury from trauma or an acute painful medical emergency.

Buprenorphine Injection

Recently Indivior, a spin-off of Reckitt Benckiser Pharmaceuticals (which makes Suboxone), submitted a New Drug Application to the Food and Drug Administration on a subcutaneous injection formulation of buprenorphine. 

A once-a-month injection would be a significant advance for opioid administration because it would significantly reduce the risk of diversion.  A patient could hardly be accused of giving away or selling a drug that is deposited in his body, or of taking an incorrect dose.  

For this reason alone, an opioid depot formulation for a chronic pain patient with monthly administration sounds very appealing.  It might eliminate the need for pain contracts, pill counts, urine drug testing, and other indignations chronic pain patients suffer every day.  Even if another medication was needed for breakthrough pain, and drug testing was deemed necessary, the depot formulation would provide a virtually indisputable level of medication that could serve as an "internal control" for test error.  Detecting the depot med at unexpected levels would alert the prescribing physician to the inaccuracy of the test rather than suggest misuse or abuse.

Nevertheless, buprenorphine is not the right opioid for once-a-month dosing.  In a 2015 paper, lead author Dr. Yury Khelemsky described a horrifying case that illustrates the dangers inherent in daily buprenorphine use.  In this case, a patient with a history of drug addiction who was being treated successfully with Suboxone suffered a broken neck that required emergency surgery.

During the procedure, the anesthetized patient began to move in response to surgical stimulation, i.e., due to pain.  Despite increasing the amount of two anesthetics, Propofol and Reminfentanil, the patient continued to move.  Only after receiving yet another drug (Ketamine) did the patient remain motionless during the delicate procedure.  During a subsequent back surgery following discontinuation of Suboxone and replacement with short-acting opioids, roughly half as much Propofol and Remifentanil provided adequate anesthesia without the addition of Ketamine. 

Khelemsky noted that as little as 8 mg Suboxone (one third of the daily dose the patient was receiving), blocks the activity of hydrocodone for up to five days, and recommended discontinuing buprenorphine at least 72 hours prior to elective surgery.  This is cold comfort to a patient requiring emergency surgery -- which could be anyone.  

An injectable depot formulation of buprenorphine would substantially increase the risk of severe and possibly untreatable pain in an emergency situation, since a depot, once injected, cannot simply be discontinued as a pill would be.  Indeed, surgery may be needed to remove the depot and halt continued administration, while existing amounts of long-acting buprenorphine in plasma may necessitate higher, riskier doses of anesthetic to surgically treat the acute injury -- all while risking inadequate pain treatment.

Inexplicably, the extensive prescribing information on a random sample of buprenorphine products contains no warnings to either patients or prescribers of the risk that pain relief from an acute medical condition, trauma or surgery may be inadequate, or that buprenorphine should be discontinued days or weeks before elective surgery. 

Ironically, one package insert warns that additional analgesia may be required during childbirth, yet it fails to warn of any other situation that may require analgesia, or how analgesia can be accomplished when considering the unique pharmacology of buprenorphine.  

This seems to reflect the mindset of Kolodny and others in the addiction treatment industry, who always seem to minimize the significance of even the most severe pain encountered by an individual when compared to the perceived societal consequences of addiction.  I wonder how many pain patients or addicts would choose such a long-acting opioid if they understood the possibility that their severe acute pain could not be controlled.

The FDA committee tasked with reviewing Indivior’s new drug application is taking public comments.  I urge anyone concerned about this new buprenorphine formulation, and the failure to warn of the possibility of untreatable acute pain when taking any buprenorphine product, to provide comments by clicking here.

Comments can be submitted through October 27, 2017.  If received by October 17, they will be provided to the committee, which is scheduled to meet on October 31.  Comments received after October 17 will be taken into consideration by the FDA. 

Jane Babin, PhD, is a molecular biologist and a biotechnology patent attorney in southern California.

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.

Study: Suboxone Usually Fails To Stop Opioid Use

By Pat Anson, Editor

A drug widely prescribed to treat opioid addiction fails so often that two-thirds of the pain patients who took it during addiction treatment wound up getting opioid prescriptions again, according to a large new study by the Johns Hopkins Bloomberg School of Public Health.

Researchers analyzed pharmacy claims for over 38,000 people who were prescribed Suboxone (buprenorphine) between 2006 and 2013, and found that 67 percent of them filled a prescription for an opioid painkiller in the year after Suboxone treatment.

Nearly half of the patients – 43 percent -- filled an opioid prescription during treatment. Most patients continued to receive similar amounts of opioids before and after Suboxone treatment.

Suboxone is a combination of two different medications: buprenorphine, a short-acting opioid similar to methadone, and naloxone, an anti-overdose drug.

During most of the years analyzed in the study, Suboxone was the only combination of buprenorphine and naloxone that was available. It is now sold under several different brand names.

The Johns Hopkins study, which was funded by Centers for Disease Control and Prevention, found that about two-thirds of the patients who received Suboxone stopped filling prescriptions for it after just three months.

The findings, published in the journal Addiction, raise questions about the effectiveness of Suboxone and addiction treatment in general, at a time when the federal government is spending hundreds of millions of dollars to subsidize the addiction treatment industry.

"The statistics are startling," said lead author G. Caleb Alexander, MD, "but are consistent with studies of patients treated with methadone showing that many patients resume opioid use after treatment."

Researchers say the continued use of pain medication during and after addiction treatment suggests that many patients did not have well-coordinated treatment for their addiction or their chronic pain.

“There are high rates of chronic pain among patients receiving opioid agonist therapy, and thus concomitant use of buprenorphine and other opioids may be justified clinically. This is especially true as the absence of pain management among patients with opioid use disorders may result in problematic behaviors such as illicit drug use and misuse of other prescription medications,” Alexander wrote.

Prescriptions for Suboxone and other brands of buprenorphine have soared in recent years as the U.S. grapples with an “opioid epidemic” that was initially fueled by painkillers, but is now increasingly caused by heroin and illicit fentanyl. Sales of buprenorphine now exceed $2 billion annually and are likely to keep growing.

Last year the federal government nearly tripled the number patients that can be treated with buprenorphine by an eligible physician. Raising the limit from 100 to 275 patients was intended to give addicts greater access to treatment, especially in rural areas where few doctors are certified to prescribe buprenoprhine.

An additional $1 billion in funding for addiction treatment was approved by Congress last year under the 21st Century Cures Act. Much of that money will be used to pay for buprenorphine prescriptions.

Addicts long ago discovered that buprenorphine can be used to get high or to ease their withdrawal pains from heroin and other opioids. Buprenorphine is such a popular street drug that the National Forensic Laboratory Information System ranked it as the third most diverted opioid medication in the U.S. in 2014.