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..

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. 

Civil Rights Case Gives Hope to Pain Patients

By Richard Dobson, MD, Guest Columnist

People with chronic disabling pain frequently complain that doctors discharge them from their practice because of the medications they take. Sometimes doctors refuse to accept patients who are taking opioid pain medications, even though the medications treat a legitimate medical condition.

There may be hope that such actions will be considered violations of the civil rights of patients.

This week the Civil Rights Division of the Department of Justice (DOJ) signed a formal agreement with Selma Medical Associates, a large primary care practice in Virginia, that may open the door for people with chronic pain to regain their full access to medical care.

Selma Medical refused to schedule a new patient appointment for a man who was taking the addiction treatment drug Suboxone. He filed a civil rights complaint asserting that his rights were violated because has a disability.

According to the complaint, Selma Medical “regularly turns away prospective new patients who are treated with narcotic controlled substances such as Suboxone.”

The DOJ and Selma Medical settled the complaint out-of-court. The full agreement can be read here.

In essence, Selma Medical agreed to stop discriminating on the basis of disability, including opioid use disorder (OUD). The settlement identifies several specific ways that Selma Medical was violating the civil rights of people with disabilities.

“By refusing to accept the Complainant for a new family practice appointment solely because he takes Suboxone, Selma Medical discriminated against him by denying him the full and equal enjoyment of the goods, services, facilities, privileges, advantages, or accommodations of Selma Medical.

By turning away the Complainant and other prospective patients who are treated with narcotic controlled substances, including Suboxone, Selma Medical imposed eligibility criteria that screen out or tend to screen out individuals with OUD.

Further, Selma Medical failed to make reasonable modifications to policies, practices, or procedures, when such modifications are necessary to afford such goods, services, facilities, privileges, advantages, or accommodations to individuals with disabilities.”

In the agreement, Selma Medical agreed to stop discriminating now and in the future. The staff and administration are also required to undergo intensive training on the implementation of the Americans With Disabilities Act (ADA).

Importantly for pain patients, the agreement applies to people taking “narcotic medications” for any reason and is not limited to people who are taking Suboxone for OUD. The agreement does seem to imply that people taking opioid medications also have their civil rights violated if they are refused medical care on the basis of their diagnosis and their use of opioids.

A former staff attorney in the DOJ’s Civil Rights Division agrees.  

“This formal settlement agreement from DOJ affirms that discrimination in access to medical treatment based solely on an individual’s use of a particular medication — in this case, a narcotic controlled substance — may violate the law,” says Kate Nicholson, a pain patient and civil rights attorney who helped draft federal regulations under the ADA.

Anyone who has chronic pain and who is discharged from a practice or refused admission to a medical practice should let the medical staff know that this is a violation of the ADA. Show them the agreement between Selma Medical and the DOJ. Then if the medical practice still refuses care, file a formal complaint with the Office of Civil Rights. Instructions on filing can be found here.

As part of the settlement agreement, Selma Medical had to pay $30,000 to the complainant for “the discrimination and the harm he has endured, including, but not limited to, emotional distress and pain and suffering.” Selma Medical also had to pay a civil penalty of $10,000.

It seems to me that the substance of this agreement gives real hope to the chronic pain community that discrimination based on disability, even if the disability is based on pain, is illegal and violates their civil rights.

Richard Dobson, MD, worked as a physician in the Rochester, New York area for over 30 years, treating and rehabilitating people suffering from chronic pain, mostly as the result of work or motor vehicle accidents.  He is now retired.  

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.

Life After Pain Meds

By Dana Stephenson, Guest Columnist

It was a warm October afternoon in 1997 when my boyfriend called and asked if I wanted to go for a ride. Being from the northeast and motorcycle season was almost coming to an end, I said sure.

I often wonder how my life would have played out if I had just stayed home that day.

It started out as a normal ride with another friend, until the friend took off down a back road. Being just 18, my boyfriend took off after him. Long story short, the road turned and we did not. We slammed head-on into a telephone pole at 85 mph. The brakes on a motorcycle don't work so well when the wheels aren't touching the ground.

I was airlifted to a hospital and was in critical condition for several weeks. I spent 10 months in the hospital and had at least eight surgeries for a fractured spine and pelvic bone, pierced colon, and bruised heart, lungs and kidney. On the outside, I only had a few scratches but I was lucky to be alive at all, considering I wasn't wearing a helmet. 

Sadly, the worst was yet to come.  I kept asking the nurses, “Where’s Mike?” The nurses would act like they couldn't hear me. I understand now they were just doing their job, but at the time I thought I was going crazy.

Three days into my hospital stay, I asked my dad the same question. He gave a simple reply, four words that I'll never forget: "He didn't make it."

Not only was this my first experience with broken bones, surgery and stitches, it was also my first experience with death.

Pain medications were necessary, along with some counseling. I made it out of the wheelchair, off the walker, and then finally the crutches. The doctors called me a walking, talking miracle.

After a few years they transferred me to pain management and I slowly began developing a new problem. To people that didn't know my story, I appeared to be normal. Pharmacists always gave me the impression that they thought I was a drug addict. Why is this young, healthy-looking girl taking such high doses of painkillers? Over the years this began to bother me more and more.

Ten years after my accident, I finally decided to get a spinal fusion, hoping the pain would go away and the social judgement would finally stop. Well, that didn't go as planned. In the 10 years since my initial fracture, I had developed scoliosis. During surgery the doctor pulled so hard on my spine, trying to get it as straight as possible before screwing it in place, he ended up re-fracturing it. Now I was in worse shape than before. 

DANA STEPHENSON

Yet a new chapter of my life began. I had to accept that at age 29, I was going to have to file for disability. After a two-year struggle they approved my application, after first denying it because of my age. That's not even legal.

After 15 years of being in pain and treated like a junkie, I had enough. It was time to get off all pain medication. I went the Suboxone route and it definitely helped with the withdrawals. After a few years I quit that too.

Of course, I'm still in a lot of pain but taking the medications again is just not worth it to me. I moved away from home, so I wouldn’t be tempted to bum pills off my old connections.

I can honestly say I haven touched a pain pill in over 5 years. It's not easy, but I'm going to be in pain with or without the pills.

Dana Stephenson lives in Florida.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

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.

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. 

An Open Letter to President-Elect Trump

By Percy Menzies, Guest Columnist

Dear President-Elect Trump,

You will soon have an extraordinary opportunity to save thousands of lives with one stroke of the pen! I am talking about reducing overdose deaths from opioid overdoses. How is this possible?

We have three highly effective medications for the treatment of opioid addiction, but they are grossly under-utilized, largely due to accessibility. Two of the three drugs used to treat opioid use disorder have restrictions that have no place when overdose deaths exceed 30,000 per year. These restrictions made sense at a different time, but these barriers are now inadvertently contributing to overdose deaths.

I am specifically talking about buprenorphine, the most widely used medication in the battle against the opioid epidemic. This medication, better known by its brand name Suboxone, is an opioid with a very safe profile. Its unique pharmacology makes it almost impossible to overdose.

There are barriers to the use of this medication which made sense 14 years ago, when heroin was not a public health issue, but today they are a hindrance to saving lives.

Buprenorphine is the only drug that requires physicians to complete eight hours of training and then apply to the Drug Enforcement Administration to obtain a special exemption to prescribe it. It gets worse. Physicians can only treat 30 patients with this medication in the first year, and then they must obtain permission from the DEA to increase the limit to 100 patients. The physician also has to keep clear records and can expect a visit from a DEA agent to look at the records. 

This is a major deterrent and way too few physicians have bothered to obtain the required exemption. Any physician who has a DEA license can prescribe an FDA-approved controlled substance without restriction, but they have to deal with this barrier to prescribe buprenorphine. 

These restrictions were put in place to prevent buprenorphine from joining the opioid “pill mills” when few anticipated heroin sweeping our cities and towns. At the present time, there is no strategy in place to cut off or curtail the supply of heroin, or heroin that is laced with super potent opioids like fentanyl. Deaths from prescription opioids are declining, while deaths from heroin and fentanyl are climbing. Indeed, prescriptions for opioids drugs have fallen between 12 -25%, but the overdoses deaths have not declined. 

Yes, buprenorphine is being diverted, but most experts believe that is due to the lack of treatment. Patients desperately seeking treatment are purchasing the drug on the streets. Many experts believe that if patients have expanded and easier access to buprenorphine, the diversion will drastically reduce and more patients will be in treatment and get away from heroin.

Several steps have been taken to address this catastrophic problem, but these steps are woefully inadequate. Expansion of the needle-exchange programs and the widespread distribution of the opioid overdose drug naloxone (better known by the brand name Narcan) are welcome and should be expanded, but they are at best palliative in nature. These measures do little to address the underlying addiction.

The federal government is increasing the patient limits for buprenorphine for selected specialists from 100 to 275, and will also allow nurse practitioners and physician assistants to complete the required training and obtain the DEA exemption to prescribe buprenorphine. These are welcome steps, but fall far short of the response required to expand treatment and reduce deaths. 

You got elected on a law-and-order platform and a promise to reduce the flow of heroin coming in from Mexico. Almost 50 years ago, Richard Nixon got elected on a similar platform.  He too faced an unprecedented public health epidemic of heroin addiction – one that is nowhere close to what we are facing today.  

President Nixon is remembered for taking a bold measure, which at that time was controversial. He initiated the opening of methadone clinics, which for the first time provided evidence-based treatment for heroin addicts. This measure reduced overdose deaths, protected society from criminal activity, and allowed these patients to become productive members of society.  For the first time in the dark and checkered history of our nation, addiction was treated as a chronic healthcare issue and not a criminal activity. 

Nixon went a step further to curb the supply of heroin coming into this country. He put political pressure on France to shut down the illegal labs processing Turkish-grown opium into heroin. Turkey also complied with the strong U.S. demand to curb the illegal cultivation of opium. Who can forget The French Connection, the thriller movie about this operation.

Mr. Trump, you have an extraordinary opportunity to lift the present restrictions on buprenorphine through executive order, to lure patients away from heroin and drastically reduce overdose deaths. Your action would provide increased treatment and not just palliative care.

Furthermore, you are in the best position to bring pressure on Mexico to eliminate the opium processing labs and drastically reduce heroin coming into this country.  An epidemic is best treated when effective treatment is combined with eliminating factors contributing to the spread of the epidemic. In this case, it is the supply of heroin.

This one single action will earn you the gratitude of tens of thousands of families terrified at hearing a knock on the door informing them of the death of a loved one. You will also earn the gratitude of millions of patients suffering from chronic pain, who have been needlessly cut off from prescription opioids because of the overreaction of regulators and many physicians.

You will be remembered in history for a bold action that saved a generation from succumbing to a man-made epidemic.

Percy Menzies, M. Pharm, is the president of the Assisted Recovery Centers of America, a treatment center based in St Louis, Missouri.

He can be reached at: percymenzies@arcamidwest.com

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.

New Rule Expands Access to Buprenorphine

By Pat Anson, Editor

This week marks the start of a major expansion in access to buprenorphine – a medication that is both widely praised for treating opioid addiction and also blamed for fanning the flames of abuse and diversion.

The Department of Health and Human Services (HHS) updated a federal rule, nearly tripling the number patients that can be treated with buprenorphine by an eligible physician.

Raising the limit from 100 to 275 patients is intended to give addicts greater access to buprenorphine, especially in rural areas where few doctors are certified to prescribe the drug. According to HHS, over two million people who are dependent on heroin and other opioids could benefit from buprenorphine treatment.

“For too long, addiction specialists like me have had to turn patients in need away from treatment that might save their lives, not because we don’t have the expertise or capacity to treat them, but because of an arbitrary federal limit,” said Dr. Jeffrey Goldsmith, President of the American Society of Addiction Medicine .

But critics of the rule change say there will be a price to pay.

“Buprenorphine is one of the most abused pharmaceuticals in the world,” warns Percy Menzies, president of Assisted Recovery Centers of America, which operates four addiction treatment clinics in the St. Louis area.

“Sales of buprenorphine formulations have exceeded $2 billion a year, but we have not had any lessening of heroin addiction. Increased access to buprenorphine and increased availability of potent heroin and heroin laced drugs like fentanyl will only exacerbate the problem.”

The problem with buprenorphine is that it’s an opioid that can be used to treat pain or addiction. When combined with naloxone, buprenorphine reduces cravings for opioids and lowers the risk of abuse. For many years the drug was sold exclusively under the brand name Suboxone, but it is now produced by several different drug makers and is sold in tablets, sublingual films and even an implant.

Addicts long ago discovered that buprenorphine can also 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 buprenorphine as the third most diverted opioid medication in the U.S. in 2014. 

“Too many physicians erroneously believe that naloxone in the formulation makes the drug safe,” Menzies said in an email to Pain News Network. “Increasing the limit is definitely going to increase diversion. The majority of the physicians prescribing buprenorphine do not provide any comprehensive relapse prevention counseling, random drug testing, etc. In the absence of standards for treating addictive disorders, anything goes and will be no different than treating chronic pain.

“We saw the problem with prescription opioids when opioids were promoted as safe and non-abusable in the treatment of chronic pain. Very quickly the numbers grew into the tens of millions and the addiction exploded. The unintended victims were the patients in genuine chronic pain.”

Menzies uses buprenorphine as an initial treatment for opioid addiction in his clinics, but prefers another medication -- naltrexone -- for long-term maintenance therapy. He says doctors who rely on buprenorphine exclusively will, in effect, be sentencing their patients to lifetime use of the drug.     

"Financial Opportunity" for Doctors

HHS acknowledges there could be “unintended negative consequences” to increased prescribing of buprenorphine. One is diversion. Another is an increase in patient volume, physician profits and buprenorphine “pill mills” – which are already popping up in states like Florida. Patients typically pay cash for buprenorphine at those clinics and receive little or no addiction counseling or services.  

“This proposed rule directly expands opportunities for physicians who currently treat or who may treat patients with buprenorphine,” HHS said in an extensive analysis of the rule change. “We believe that this may translate to a financial opportunity for these physicians.”

HHS estimates the cost of treating new buprenorphine patients at up to $313 million in the first year alone. Many of the patients are low-income and the bills for treating them – about $4,300 annually for each patient – will often be covered by Medicaid. The additional cost of treating these patients, according to HHS, will be offset by the health benefits achieved by getting addicts into treatment, which the agency generously estimates at $1.7 billion.

The Obama administration asked Congress for nearly $1 billion in additional funding to help pay for addiction treatment, but didn’t get it in when Congress passed the Comprehensive Addiction and Recovery Act (CARA Act). The President reluctantly signed the bill into law anyway.

A little noticed provision of the CARA Act is that it expands access to buprenorphine even further. Currently only a trained and certified physician can prescribe buprenorphine, but CARA requires HHS to update its rules within 18 months to allow nurse practitioners and physician assistants to prescribe buprenorphine, provided they undergo training first.

How can buprenorphine diversion be prevented when access to it is rapidly increasing?

One solution proposed by Menzies is to change the classification of buprenorphine from a Schedule III controlled substance to a Schedule II drug – the same classification change that hydrocodone went through in 2014. Such a move would limit buprenorphine prescriptions to an initial 90-day supply and require patients to see a doctor for a new prescription each time they need a refill.

“We are caught between a rock and a hard place. We need to increase access to buprenorphine and it will lead to increased diversion and abuse, and therefore I am recommending changing the schedule,” Menzies said in his email to PNN.

“This is the psychotic state of affairs! No chronic condition/disease/disorder has ever been successfully treated with an addicting drug and we think we can do it for opioid addiction!”

FDA Approves New Drug Implant

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved the use of a new drug implant for the treatment of opioid addiction.  Probuphine is the first implant of its kind approved by the agency and could potentially be a game changer for other medical conditions such as chronic pain that require steady doses of medication around-the-clock.

Probuphine is designed to be inserted into the arm beneath the skin, where it delivers a low dose of burprenorphine directly into the bloodstream for up to six months.  

Buprenorphine is an opioid itself, but when combined with naloxone, the medication reduces cravings for opioids. Until now the drug has only been available as a pill or film strips placed under the tongue.

For many years buprenorphine was sold exclusively under the brand name Suboxone, but several pharmaceutical companies have entered the lucrative addiction treatment market and now make versions of their own. As many as 2.3 million people who are dependent on opioid pain medication or heroin could benefit from buprenorphine treatment,

FDA approval was a major win Braeburn Pharmaceuticals and its partner, Titan Pharmaceuticals (OTC: TTNP), which holds the rights to the implant technology. Titan and Braeburn were stunned in 2013 when the FDA denied approval of the implant and asked for new clinical studies proving Probuphine’s effectiveness.  

Results from a recent Phase III study showed that over 85% of the patients who had the implant abstained from using illicit opioids for six months, compared to about 72% of patients who used buprenorphine film strips that were taken daily.

"Opioid abuse and addiction have taken a devastating toll on American families. We must do everything we can to make new, innovative treatment options available that can help patients regain control over their lives,” said FDA Commissioner Robert Califf, MD. “Today’s approval provides the first-ever implantable option to support patients’ efforts to maintain treatment as part of their overall recovery program.”

Expanding the availability of addiction treatment is a major goal of the Obama administration. The White House has asked Congress for an additional $1.1 billion to fight opioid abuse, with much of the money earmarked for addiction treatment. The administration has also proposed doubling the number of patients that doctors can treat with buprenorphine from 100 to 200.

Buprenorphine can be abused and is a popular street drug that is used to get high or to ease withdrawal pains from illegal opioids such as heroin. An implant will be much more difficult to abuse, since it can’t be crushed or liquefied for snorting or injecting. It’s also less likely to be diverted.

Probuphine is expected to cost about $1,000 a month. It consists of four, one-inch-long rods that are implanted under the skin on the inside of the upper arm. Administering Probuphine will require special training because it must be surgically inserted and removed.

The most common side effects are pain at the implant site, as well as itching, redness, headache, depression, constipation, nausea, vomiting, back pain, toothache and oral pain. The FDA is requiring post-marketing studies to establish the safety and effectiveness of the implants.

Probuphine was developed using a patented implant technology called ProNeura, which is designed to provide continuous levels of medication in the blood. Titan is also developing implants to treat Parkinson’s disease and hypothyroidism, and its CEO told Pain News Network that ProNeura could also potentially be used to deliver pain medication.

“Clinical studies will need to be done to establish the ability, but the drug levels can certainly be delivered that are going to be beneficial for treating chronic pain,” said Titan CEO and President Sunil Bhonsle. “There are many applications for this technology and I think the medical community is now more in tune with looking at long-term delivery technology in the chronic disease setting.”

“It is part of our plan to move into pain because pain and opioid addiction are so interconnected and we think there are ways, by treating patients with a less abuse-able formulation, you could actually help alleviate the addiction problem,” Behshad Sheldon, President and CEO of Braeburn, told PNN in an earlier interview.