Buprenorphine: Another Tool in the Analgesic Toolbox?
By Larry Beresford
In an opinion piece posted in April 2019 on the Washington, DC–based news site The Hill, Craig D. Blinderman, MD, director of the Adult Palliative Care Service at Columbia University Medical Center in New York City, asserted that buprenorphine, a mixed opioid agonist/antagonist, was an important but often overlooked analgesic treatment option in the context of the ongoing opioid overdose crisis.1
Overdoses from both prescribed analgesics and illicit opioids continue to be a growing problem in this country, with important implications for the practices of hospice and palliative care providers. Increasing numbers of their patients may present with both a history of or identified risk for opioid misuse and pain resulting from a serious illness. Managing those two conditions at the same time presents clinicians with a real dilemma, for which they need to find an appropriate balance. And buprenorphine might offer a helpful alternative in some cases, Blinderman said.
According to him, buprenorphine has applications for a range of patients, including those with sickle cell disease, chronic neuropathic pain, and cancer-related pain. "Most hospice and palliative medicine providers are not familiar with prescribing it, but that is changing," he said. Academy members are starting to pay more attention, as are bodies like the National Institutes of Health, which has called for research proposals to investigate interventions using buprenorphine.
Today, buprenorphine is used more widely in Europe than the United States. It has been approved by the US Food and Drug Administration as a medical office–based medication for opioid use disorder (MOUD), but for a clinician who does not hold an appropriate board certification to prescribe buprenorphine in this way, they must complete 8 hours or more of training and obtain a provider waiver from the Substance Abuse and Mental Health Services Administration (SAMHSA).
However, buprenorphine has been approved in intravenous form as an analgesic in the United States since 1980, and a waiver is not required if prescribing it for pain. However, the prescriber must be registered with the Drug Enforcement Agency (DEA) and authorized to prescribe controlled substances by the jurisdiction where they are licensed to practice. It also is available in transdermal patches (trade name: Butrans) and buccal films (Belbuca) for around-the-clock treatment of moderate-to-severe chronic pain. Sublingual formulations, in combination with naloxone (eg, Suboxone, Zubsolv), are indicated for treatment of opioid dependence. However, clinicians always should check with local and state authorities to assess any regulations that may impact prescribing buprenorphine for acute or chronic pain because these laws may vary widely from location to location.
And medical management gets more complicated when the therapy is planned for treating both pain and opioid use disorder (OUD) at the same time. A recent article in the Journal of Hospice and Palliative Nursing explores these complexities.2
Many practitioners note that the regulatory environment for prescribing buprenorphine, a reflection of the national response to the overdose epidemic, also creates challenges, with stories of unannounced visits from the DEA and even temporary clinic closures—although recent communication from the agency encourages practitioners to take the training and use the medicine appropriately.
Chad Kollas, MD FACP FAHPM, medical director of palliative and supportive care at the University of Florida Health Cancer Center in Orlando, represents AAHPM at the American Medical Association (AMA) House of Delegates, where he chairs the multispecialty Pain and Palliative Medicine Section Council. "The message we have shared with the AMA is that we need more people prescribing buprenorphine for OUD. But be careful; it could put you on somebody's radar," Kollas said. Representatives from other specialty societies in the Section have expressed concerns that prescribing buprenorphine, or even just obtaining the waiver to prescribe it, placed them at higher risk for federal regulatory scrutiny.
Lack of insurance coverage of buprenorphine is another barrier, with some insurers requiring prior authorizations or implementing quantity limits to what is covered when used for the treatment of pain.
Finding Peer Support
AAHPM Connect, the Academy's online community for members, has hosted a lot of dialogue about buprenorphine since Zachary Sager, MD, of the VA Boston Healthcare System posted a query in October 2019. That initial post generated 72 responses, inspiring Sager to create an informal peer support network simply by sharing a link to a Google Docs questionnaire. More than 200 palliative care clinicians have since responded with interest.
The group has planned a series of recorded interactive webinars and discussions, the first of which was held in January. "The emerging online [group] aims to develop regular case-based discussions so that we can talk together about the steps to take, allowing [participants] to ask questions and share their concerns," Sager said. "As there are quite a few folks who have not yet completed the training (for a buprenorphine waiver) but are interested in pursuing it, our first step is to try to bring these clinicians into the fold by starting at a basic level, rather than immediately taking on advanced topics."
Successive webinars will get progressively more in depth, focusing on the specifics of buprenorphine prescribing and managing addiction in hospice and palliative medicine settings. "The evidence for buprenorphine for MOUD is really good, but I think we are all a bit in the dark in trying to understand how to use it for folks who have both pain and addiction," he said.
This is an interesting time for the drug and for palliative care in general, Sager added, because there are a lot of people who have been on chronic pain medications for a long time, and their pain still needs to be managed in light of the addiction crisis. "We recognize the importance of pain management to our field, and we see that the pendulum may have swung to where we were using opioids without considering their long-term sequalae."
Research has shown that when used to treat patients with underlying addiction issues, buprenorphine is effective in reducing overdose deaths and in helping patients remain on treatment. "The key point is our focus on the relief of suffering," Sager said. "But now we have a more nuanced understanding of that suffering." It isn't just driven by cancer pain. Other forms of suffering include psychological, and addiction itself can be a significant source of suffering for patients.
"Patients don't stop being who they are when they get a serious illness," he said. "Now we're becoming more aware of their needs. Once you acknowledge that your role includes addressing that kind of suffering, then you may need to consider other approaches."
Most palliative care providers are experienced with using methadone for pain, said Julie Childers, MD MS, associate professor of medicine at the University of Pittsburgh. "We're not as familiar with its applications for addiction, but increasingly, physicians and other providers are extending their practice to include addiction treatment. MOUD is good evidence-based treatment, and given how common addiction is, we will see significant numbers of patients who may have trouble accessing addiction treatment because of their serious illness," she said.
"If they can make it to see us in hospice and palliative care, this is a great service for us to offer to patients, if we can learn enough about how to use it. Addiction is often made worse or left untreated in patients' encounters with the medical system. Can we in hospice and palliative care provide some basic addiction treatment for these patients?" The first thing clinicians should do is start asking their patients about substance use and screening for it. "With buprenorphine, start with one or two patients in your practice who have nowhere else to go for this treatment, and then see how you do," she said.
Buprenorphine offers a number of safety features compared with other opioids, Blinderman noted. Patients on buprenorphine seem to become tolerant to the respiratory depression effects, so they don't face the same risk for overdose when doses are increased for analgesia. The drug also is associated with less analgesic tolerance than other opioids and seems to have fewer long-term opioid-related complications, such as effects on the immune and endocrine systems.
Buprenorphine's safety profile compares favorably with methadone, a synthetic opioid that is used both for pain management in hospice and palliative medicine and also for opioid maintenance therapy. It also appears to lack methadone's risk for sudden cardiac death. This is probably because buprenorphine carries less risk of prolonging the QT interval, as measured on an electrocardiogram, to dangerous levels that could cause Torsades de pointe.3
Moreover, buprenorphine has been shown to be effective for cancer pain, noncancer pain, and neuropathic pain because of its unique mechanisms of action. "There is no evidence that buprenorphine is superior for treating severe chronic pain than the more common analgesics we use like morphine," Blinderman said. "But because palliative care providers increasingly are seeing patients with a history of or risk for substance use disorder in the setting of serious illness that causes pain, from a harm reduction standpoint, we would want to avoid oxycodone or similar medications that might cause relapse of opioid misuse for those patients."
But buprenorphine presents challenges of its own because of its unique properties, Blinderman noted. Its partial agonism at the mu opioid receptor and other actions are not necessarily understood by clinicians. Converting patients to and from other opioids can be tricky. Patients on opioid therapy who are being transitioned to buprenorphine often experience withdrawal symptoms. And if the patient undergoes surgery or has an acute exacerbation of pain while on high doses of buprenorphine, analgesia may be more difficult to achieve.
"For patients who have a longer life expectancy, such as cancer survivors who still have a lot of pain, I often favor buprenorphine because they will be on it for a long time. To me, it's an issue of safety," Blinderman said, adding that he would like to see a national clinical education program on the drug.
In a 2012 article in the Journal of Supportive Oncology, "Twelve Reasons for Considering Buprenorphine as a Frontline Analgesic in the Management of Pain,"4 and in follow-up abstract presentations,5 Mellar Davis, MD, a member of the palliative care department and section head for the Geisinger Medical System in Danville, PA, has elaborated on the benefits of buprenorphine and its advantages compared with other opioids.
According to Davis, it has a complex and unique pharmacology with some unique analgesic properties, including non-crosstolerance to other opioids; in addition, it is less suppressive of the pituitary and hypothalamus glands, and it is relatively safe for liver and kidney function. As with methadone, it is long-acting and can be given sublingually—which might be important to some patients, he said. "It depends on the particular clinical situation. There are some patients for which you wouldn't want to use it. But it has its niche in palliative care and pain management. Let's consider where it fits into the ladder of analgesics, following the historical precedence of methadone," he said.
"If we're going to manage our patients' pain and relieve their suffering, we ought to be using all of the tools in the analgesic toolbox and using them well," Davis added. "Yes, I use buprenorphine with my patients. We also use a lot of other opioid analgesics here. We need to keep an open mind on what's going to work best for which patient."
- Blinderman CD. Buprenorphine: a life-saving medication that's being overlooked in the opioid crisis. The Hill. April 12, 2019
- Jones KF. Buprenorphine use in palliative care. J Hosp and Palliat Nurs. 2019;21(6):540–547.
- Poole SA, Pecoraro A, Subramaniam G, Woody G, Vetter VL. Presence or absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence. J Addict Med. 2016;10(1):26–33.
- Davis MP. Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012;10(6):209–219.
- Davis M. Why you should consider buprenorphine for cancer pain (Abstract TH321). J Pain Symptom Manage. 2014;47(2):399–400.
Buprenorphine Waivers and Other Resources
The American Society of Addiction Medicine has an online resource page for buprenorphine waiver management, including courses on its eLearning Center on treatment of OUD that could qualify clinicians for the buprenorphine clinical waiver. Physicians and other qualified practitioners (physician assistants and advanced practice registered nurses) who want to prescribe buprenorphine for opioid addiction treatment need 8 or more hours of training.
Clinicians also can apply directly on the SAMHSA website. The Providers Clinical Support System representing a coalition of interested professional organizations also provides information, resources, and mentoring on MOUD.