A two-part blog post which explores how buprenorphine can help people living with serious illness – especially those with pain and opioid use challenges.

Pharmacist handing patient medication

Case Study + Introduction

Meet Mr. D, a 54-year-old male with stable Stage IV lung cancer who is under active treatment with immunotherapy. He has suffered from chronic pleuritic pain since a surgical resection 3 years ago, and has used a stable dose of a fentanyl patch and oxycodone (200 mg morphine equivalents daily) for pain management for the past several years. In recent months, Mr. D has developed opioid misuse behaviors (e.g. running out early, self-escalating doses, concurrent alcohol use, and presenting to the emergency room for refills).

Mr. D meets criteria for an opioid use disorder (OUD) (expand Figure 1 below). Therefore, he and his palliative care team make a shared decision to initiate buprenorphine/naloxone (prescribed by an X-waivered palliative care clinician, explained in more detail later).

Within a few weeks of starting on buprenorphine/naloxone, Mr. D achieved pain control on a dose of 4 mg buprenorphine/1 mg naloxone (three times/day). He has been doing well on this regimen – with stable behaviors, improved pain, and better quality of life. Intermittently, a full-opioid agonist is added to his regimen as needed, to help with pain from a chest tube. He recently told his palliative care team, “My life has improved so much this past year. I feel physically and emotionally better than I have in years, even though I am living with Stage IV cancer.”

The 4 C's can be a helpful mnemonic for 12 DSM diagnostic criteria that establish both the diagnosis of OUD and the severity (from mild, moderate, severe). In this case, Mr. D presents with:

4 C: Craving
DSM-5 Criteria: Strong desire or urge to use an opioid
Possible manifestation of OUD: Patients can often understand this term and respond to questions about craving directly; note that pain can be a sign of craving

4 C: Control (lack of)
DSM-5 Criteria: Use of an opioid in increased amounts or longer than intended
Possible manifestation of OUD: The patient is asked to limit their opioid quantity to 5 per day, and is given a one-week prescription that reflects this amount, but still runs out 3 days early

4 C: Consequences
DSM-5 Criteria: Continued opioid use despite problems socially, interpersonally, medically
Possible manifestation of OUD: Strained relationships with family and clinicians surrounding opioid use; continued use despite being told by clinicians that they are being physically or psychologically harmed by the opioid

4 C: Compulsive Use
DSM-5 Criteria: Use of an opioid in physically hazardous situations
Possible manifestation of OUD: Self-escalation of opioid dosing; when asked, patient may say take the opioid “without even thinking about it”

For more on possible manifestations, click here.

As palliative care clinicians, these are words we like to hear. We strive to achieve symptom control and quality of life for all our patients, and are always looking for new tools that strike the balance between efficacy, safety, and versatility. Buprenorphine has the potential to be an important option.

In this two-part blog post, we explore the ways buprenorphine can help people living with serious illness – especially those who experience a range of both pain and opioid use challenges. In part one, we provide background on buprenorphine, including its pharmacology. And later, in part two, we discuss considerations for prescribing, how to prescribe, and potential barriers to use.


The Importance of Buprenorphine as an Analgesic

Buprenorphine can be an effective analgesic with fewer adverse effects than traditional opioid agonists, such as morphine or oxycodone. Some advantages of prescribing buprenorphine for pain include:

  • Decreased risks of respiratory depression, sedation, euphoria, craving, dysphoria, hyperalgesia, and constipation; and other GI side effects
  • Less effect on the hypothalamic pituitary axis, thus carrying less risk for hypogonadism and its associated complications, such as sexual dysfunction, decreased libido, and osteopenia
  • An association with less QTc prolongation, arrhythmia, and sudden death, when compared to methadone
  • Safe for use in renal failure or during dialysis, and well tolerated in patients with liver disease
  • If buprenorphine doses have been stable, co-prescribing with short-acting opioid agonists can be done safely, such as for post-operative pain, as Mr. D’s palliative care team did, in the case presented earlier

How Buprenorphine Works

Given the advantages of buprenorphine – and we would argue that these advantages are particularly germane in individuals at the intersection of serious illness and chronic pain – why isn’t it more widely used in palliative care settings? The three main reasons may be: lack of clinician familiarity; relative expense; and requirements for prior authorization. However, we routinely use buprenorphine in our palliative care practices and help others get started. It can be done. Let’s get more familiar with buprenorphine and discuss how it works.

Buprenorphine Pharmacology

Most clinicians know buprenorphine for its efficacy in the treatment of OUD, including reduction in opioid mortality and illicit opioid use. However, buprenorphine was originally developed as an analgesic — relieving pain by acting on the central nervous system. Because of its unique properties, buprenorphine is effective for both pain and OUD.

  • Buprenorphine acts as a partial agonist at the µ opioid receptor; an antagonist at the kappa and delta-opioid receptors; and a full agonist at the opioid receptor-like receptor.
Buprenorphine pharmacology
Figure 1: Efficacy and tolerability of buprenorphine compared to full opioid agonists used for chronic pain. (A) Potential mechanism of action for buprenorphine and (B) Conceptual representation of possible effects compared with those of full opioids agonist such as morphine, oxycodone, hydromorphone. // Webster et al. 2020, Pain Medicine, 0(0), 1-10. “Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion." Adapted with permission.
  • Its strong affinity for the µ opioid receptor and slow dissociation may provide sustained analgesia at relatively low doses. There has been concern that as a partial µ agonist, buprenorphine may have limited potency, but evidence suggests it can provide analgesia similar to “full” opioid agonists (e.g., morphine, oxycodone).
  • Due to buprenorphine’s increased spinal cord activity and reduced activity in the brain, there is a decreased risk for respiratory depression and hyperalgesia.
  • Antagonist activity at the kappa and delta-opioid receptors appears to lessen craving, sedation, and dysphoria.
  • Additionally, kappa antagonism may improve the stability of comorbid mental health conditions, such as anxiety and depression

The X Waiver

Federal law requires eligible prescribers who already have a DEA license to obtain a specialty DEA X- waiver to prescribe buprenorphine for OUD. As of April 27, 2021, the waiver became more accessible, with the release of new Buprenorphine Practice Guidelines that allows DEA licensed clinicians to apply for an X waiver to treat up to 30 patients, without completing the additional educational training or attesting to the ability to refer for counseling. Importantly, clinicians still must submit a Notice of Intent to Substance Abuse and Mental Health Services Administration (SAMHSA) to obtain an X waiver, but after the completion of the Notice of Intent, a license number that begins with an X is issued.

We will go into the how-to’s of prescribing in part two of this blog post, but it’s important to note that buprenorphine can be prescribed without an X waiver – if being prescribed only for pain management. The formulation will be limited to use of the products that the FDA has approved for pain, as discussed in Part two (Figure 2). If a clinician prescribes buprenorphine for an OUD, or for pain management in the context of a co-existing OUD, as in the case described earlier, the X waiver is required. (To learn more and to obtain an X waiver, click here.)

Read on in part two, where we discuss when to consider prescribing buprenorphine for your patients, how to prescribe (e.g. getting an X-waiver), and potential barriers.

Read Part Two: The Ins and Outs of Prescribing Buprenorphine

Continue reading part two of this blog post, where we discuss considerations for prescribing, how to prescribe, and potential barriers to use.

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