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.”

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.