William C. Becker, MD

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

The goal of this activity is to understand the use of buprenorphine and other techniques to manage chronic pain.

After engaging with the content of this CME activity, you should be better prepared to:

• Appreciate psychiatry’s unique and much-needed skill set in diagnosing substance use disorders and managing co-occurring chronic pain.

• Recognize the difference between acute and chronic pain.

• Understand the role of buprenorphine in helping patients with chronic pain stop full agonist opioids.

• Generate a treatment plan that includes both pharmaco- and psychotherapeutic strategies for patients with chronic pain on opioids, with and without opioid use disorder.

This continuing medical education (CME) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership Physicians’ Education Resource®, LLC and Psychiatric Times. Physicians’ Education Resource®, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity is funded entirely by Physicians’ Education Resource®, LLC. No commercial support was received.

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource®, LLC.

FACULTY, STAFF, AND PLANNERS’ DISCLOSURES

Drs Abelleira and Becker have nothing to disclose regarding the topic of this article. Dr Edens notes she is a shareholder of Aspire-365 (a substance use disorder treatment company) and 100 Proof Living (a consulting firm addressing alcohol supplementation in the workplace); she serves on the advisory board of both companies. Dr Barry is an MPI on an NIH-funded study (1 U01 HL 150596-01) and has consulted for the Office of the District Attorney in New Haven, CT. Richard Balon, MD, (external reviewer), the staff members of Physicians’ Education Resource®, LLC, and 

 have no relevant financial relationships with commercial interests.

For content-related questions email us at 

; for questions concerning the accreditation of this CME activity or how to claim credit, please contact 

 and include “You Say Pain. I Say Addiction. Let’s Call the Whole Thing Off.” in the subject line.

Once you have read the article, please use the following URL to evaluate and request credit 

https://education.gotoper.com/activity/ptcme20nov

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The Accreditation Council of Graduate Medical Education (ACGME) requires all residency training programs to “provide instruction and experience in pain management if applicable for the specialty, including recognition of the signs of addiction.” United States psychiatry residents and all psychiatric fellows are being taught how to “prevent addiction wherever possible while effectively treating pain,” “recognize addiction in its earliest stages,” “use non-pharmacologic means wherever possible,” and to “function effectively in systems of care for 

While the current spotlight on opioid overdose and related morbidity has prompted mandates for psychiatry training programs to educate trainees in chronic pain management, the overlap between chronic pain and psychiatric illness, including alcohol and drug use disorders (AUDs, DUDs), has 

 Among people with substance use disorders (SUDs), chronic pain may be both a driver of substance use and a contributor to 

 The reverse has also been found, with substance use being associated with greater pain interference and 

 Given this high degree of overlap between chronic pain and SUD as well as other psychiatric comorbidities including depression, anxiety, and posttraumatic stress disorder

, some clinicians are suggesting the question of pain or addiction should be re-examined. Rather than treating these as distinct disorders, which reinforces siloed treatment, it may be more appropriate to consider an integrative model of “multimorbidity” (ie, multiple illnesses existing together and interacting in complex ways) and to treat chronic pain, SUDs, and co-occurring psychiatric disorders simultaneously.

“Ms Morris” is a 52-year-old female with chronic pain. She comes to see you in your outpatient clinic reporting symptoms of depression and anxiety. She has a history of AUD but denies any problems with her current use, which she describes as “a couple of beers a week, usually on the weekend” and never drinking 4 or more drinks in a 2-hour period. Her primary care doctor has prescribed oxycodone and initiated a taper 6 months earlier. After reducing from 120 mg oxycodone to 90 mg oxycodone, Ms Morris’ taper has stalled, as she cites increased pain. The primary care doctor consulted you to help determine if she has an OUD, to assess her worsening depression and anxiety, to evaluate her alcohol use, and to help develop a treatment plan.

Upon evaluation, Ms Morris does not meet criteria for DSM-5 OUD. She denies aberrant use, cravings, or any negative consequences. There is no evidence of loss of control other than a stalled taper. Certainly, tolerance and withdrawal are present, but these criteria are excluded from the symptom count criteria since an opioid is being prescribed.

It is determined that Ms Morris meets criteria for major depression. She is isolating more and has disconnected from friends. She spends most of her days on her couch at home watching television. She drinks 1 to 2 beers about 3 to 4 nights a week. She drank very heavily 2 decades ago, attending a few peer support meetings for help. She does not meet criteria for an AUD at this time.

What are the next steps? Do you refer her back to the consulting physician to continue an opioid taper because Ms Morris does not have an OUD diagnosis? What antidepressant do you recommend? What is the role of alcohol counseling and monitoring in Ms Morris’ care? What is your role in chronic pain care?

A primary reason psychiatrists are reluctant to treat chronic pain is that they typically are not trained in one of the first steps in pain management: diagnosing the underlying pain generator, such as rheumatoid arthritis or spinal stenosis. Without that step, there may be a related belief that there is no role for the psychiatrist once a diagnosis is made. Put another way, we often view chronic pain as a biomedical model. Yet, research findings in pain management instead support a biopsychosocial model, in which psychiatrists are well-versed. Additionally, psychiatrists are often uncertain what to do when a patient complains of breakthrough pain (a flare-up of pain); we fear missing a medical emergency. It would be a mistake to conclude, however, that psychiatrists are not natural and valuable members of a pain care team. Rather, close partnership with the primary care or pain provider (whoever is leading the overall pain care plan) is essential. In order to be effective members of the team, psychiatrists should keep the following key concepts in mind:

Chronic pain is recognized as “pain that persists past normal healing time and hence lacks the acute warning function of physiological nociception.”

 Pain is usually classified as chronic when it lasts more than 3 to 6 months. Acute pain (lasting less than 3 to 6 months since date of injury) is managed differently and not within the scope of general psychiatry practice. Making the distinction between acute and chronic pain is crucial and can be done through conversation and collaboration with the primary care provider or pain specialist. Additionally, psychiatrists should ask about the expected clinical course of the diagnosis, indicators of worsening illness, and when to refer a patient to the primary pain care team to clarify the process for addressing any clinical concerns.

Breakthrough pain (or pain flare-up) is common in chronic pain and not typically a marker of worsening tissue damage. Rather, abrupt changes in functional status, changes in bowel/bladder function, and new areas of numbness or weakness should prompt a call to the primary pain care treatment team.

Current guidelines recommend the use of multimodal chronic pain treatment with increased uptake of nonpharmacological pain treatment modalities as a first line approach.

 Such interventions are often broken down into active (ie, something the patient does) versus passive (ie, something that is done to the patient) therapies. The more active the therapy, the better, as they allow patients to take back some control that living with chronic pain has taken from them. Active therapies are more likely to improve physical conditioning, a benefit for both pain and general health. Physical therapies, paced physical exercise, and stretching are all beneficial.

Among the most well-studied active therapies is cognitive behavioral therapy (CBT). There are specific cognitive behavioral therapies designed to treat chronic pain (CBT-chronic pain) and SUDs (CBT-SUD) individually. Generally, CBT will ask patients to track (and focus on) symptom severity to assess whether discrete interventions are effective. However, in the case of CBT for chronic pain, patients are directed to track functioning or coping instead of symptom severity (ie, pain intensity). When faced with pain flare-ups, the CBT therapist encourages patients to engage in some physical activity and challenges the assumption that tissue damage is likely the cause of the flare-up. Three pilot studies

 have found support for the efficacy of CBT when used for both chronic pain and substance use disorders. Using CBT, patients unlearn the association between pain and substance use and instead build a repertoire of healthy non-drug related behaviors to manage pain. Mindfulness-based strategies are also emerging as beneficial not only for the management of chronic pain

, but also for use in patients with SUDs.

 Simple therapeutic interventions targeting goal-setting, distress tolerance, and activity planning are core components of both chronic pain management and SUD treatment. These are bread and butter interventions with which most psychiatrists are familiar.

Passive interventions for chronic pain include joint or muscle injections (eg, intra-articular corticosteroid injections, trigger point injections, botulinum toxin, nerve blocks), nerve stimulators, acupuncture, massage, chiropractic manipulations, application of heat/ice, and of course, medications.

When discussing the rationale for active therapies over and above passive therapies (including medications), psychiatrists will often need to educate their patients on the science of chronic pain. “But wait!” a patient might say. “You’re going to explain pain to me when I’ve been living it for 20 years?” A strong therapeutic alliance, aided by a spirit of curiosity and acknowledgement that the patient has a meaningful narrative to tell and valid life experience, is a key component for managing all medical conditions, including chronic pain.

First and foremost, patients need to hear us acknowledge that their pain is real—because it is. If you were to say, “I’m feeling cold,” only to have someone dismiss your experience as “being all in your head,” you would most likely become very irritated (and then go get a sweater). What frequently benefits patients, typically after relaying their experience, is an explanation of the science of pain. The truth is, once the site of peripheral tissue damage has healed, continued pain is transmitted from the periphery through the spinal tracts and processed in the brain. This process, in which the pain generator moves from the peripheral to the central nervous system, is called “central sensitization.” The good news is that the brain is hardwired to interact with the environment and is influenced by one’s thoughts and experiences, things that patients have control over and, therefore, can intervene upon. Psychiatrists might say, “We might not be able to fix your pain, but we can work together to make sense of your pain and get you back to living more of the life you want.”

As in Ms Morris’s case, it is common to identify heavy alcohol use in people with chronic pain, and clinicians should address and treat alcohol use. There is a common belief among patients that alcohol will dull the pain and, while they are not wrong, it requires doses consistent with binge drinking to do so. Binge drinking is associated with further trauma and associated pain. Long-term heavy drinking can actually make the pain experience worse over time and become a barrier to initiation of 

Additionally, people who use opioids, alcohol, and other drugs often develop negative emotional states between use, known as hyperkatifeia, or a hypersensitivity to emotional distress, which is itself a painful state and worsens physical pain.

 Because of overlapping mechanisms by which alcohol and opioids reduce pain, co-use of both can diminish the efficacy of either to reduce pain; in addition, co-use increases risk of falls, fractures, and non-fatal and fatal overdose. Understanding the complex interactions of chronic pain and substance use can help providers more effectively partner with patients to set goals and relieve suffering.

Once the care team has decided to use pharmacologic treatments, non-opioid analgesics should be optimized first. Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, topical anesthetics, serotonin-norepinephrine reuptake inhibitor (SNRIs), tricyclics, and antiepileptics, including gabapentinoids, are all standard pharmacotherapy for chronic pain. Psychiatrists are generally comfortable prescribing antidepressants and antiepileptics for a number of psychiatric conditions, and they can include chronic pain as 1 of these conditions. Several analgesics have dual benefit in treating specific SUDs (

Opioids have generally fallen out of favor as a treatment for chronic pain except in situations of palliative care and should be considered as third-line therapy that is monitored closely and kept at low doses. Emerging evidence indicates that long-term use of opioids for chronic pain does not substantially improve the pain experience compared to non-opioid therapies, and it is associated with more side effects and risks of harm.

 With that said, because of prescribing practices and ideas about opioids and pain over the past 2 decades, we are in a situation where many patients are on long-term opioid therapy (LTOT), sometimes at very high doses, and they continue to have chronic pain. Further, some of these patients have developed an OUD, whose treatment will now require considerations surrounding effective management of both OUD and chronic pain. Many of these patients are seen in psychiatric offices, although generally psychiatrists are focused on the patient’s comorbid mood, anxiety, trauma, or cognitive complaints.

In sum, psychiatrists are uniquely positioned to collaborate on the management of patients’ chronic pain. They have unique training in CBT and other psychotherapies. They prescribe medication that frequently overlaps with chronic pain management, and they have general knowledge of SUD treatment, including the use of buprenorphine.

Buprenorphine, originally developed as an analgesic, for a time fell out of favor in treating pain while its use in treating OUD became more prevalent. For those on LTOT, however, buprenorphine provides several benefits over full mu receptor agonists. Buprenorphine acts as a partial agonist at the mu opioid receptor (MOR), an antagonist at the kappa (KOR) and delta (DOR) opioid receptors, and a full agonist at the opioid receptor-like (ORL1) receptor.

 Buprenorphine can provide several benefits as an alternative to LTOT for patients with and without comorbid OUD. Buprenorphine’s high affinity for the MOR and slow dissociation allow for effective and long-lasting analgesia at relatively low doses.

 There is often concern among clinicians that, as a partial MOR agonist, analgesia provided by buprenorphine will reach a ceiling effect, however buprenorphine provides analgesia similar to full MOR agonists, which may in part be due to its activity at the ORL1 receptor.

 Due to increased activity in the spinal cord and reduced activity in the brain, there is a substantially-reduced risk of opioid-related adverse effects, including a ceiling effect on respiratory depression.

 Antagonist activity at the KORand DOR result in lower likelihood of misuse, reduced CNS depression, and less dysphoria.

 Patients maintained on LTOT, particularly during attempts at taper, may experience affective instability. This may be mitigated by the KOR antagonism and result in improved stability of comorbid mental health conditions.

 These effects, along with a reduced risk of tolerance and hyperalgesia, highlight the utility of buprenorphine as a safe and effective alternative to LTOT.

Buprenorphine is FDA-approved in varying formulations to treat moderate to severe pain requiring long-term opioid therapy and to treat OUD by helping patients stop their use of full agonist opioids. Yet, despite relative comfort using other medications for dual properties, many buprenorphine prescribers who treat OUD do not feel comfortable using it for chronic pain. Since 2012 the Connecticut Healthcare System of the Department of Veterans Affairs (VA) has been using buprenorphine for patients with chronic pain on moderate-to-high-dose LTOT (

). The cutoff of 50 milligram morphine equivalents (MME) per day is the point at which, compared to opioid doses less than 20 MME, 

Current guidelines focus on avoiding initiation of full agonist LTOT for chronic pain and do not mention buprenorphine analgesic formulations as alternatives. More research is needed to determine comparative effectiveness and safety of long-term buprenorphine for pain versus full agonist opioids. Our practice is to consider long-term buprenorphine analgesic formulations as alternatives to full agonist initiation especially among patients who have tried several non-opioid and non-pharmacologic treatment options and are at higher than average risk of opioid overdose. More commonly, we use buprenorphine as a tapering strategy for people already maintained on full agonist LTOT, a practice that is increasingly promoted by expert consensus panels.

When explaining the rationale for buprenorphine to patients with chronic pain on LTOT, several factors should be noted.

Persistent uncontrolled pain, despite moderate-to-high-dose LTOT (ie, the current plan is not working all that well). We often use the analogy of antidepressant treatment for depression. If, despite maximum dosing over an adequate period of time, a patient’s depression remains severe, we do not continue increasing the dose. Rather, it is standard practice to conclude that the treatment is not working and initiate a different treatment. The same is true with opioids.

Evidence of opioid tolerance. Lower doses used to be effective but are no longer effective. Thus, because of tolerance, the risks but not the benefits of high-dose therapy are mounting. To reduce opioid tolerance, we have 2 choices: either a slow taper or a switch to buprenorphine. Offering this constrained choice allows patients to feel more in control of the treatment plan. In a controlled case series, we found that two-thirds of patients, when offered this choice, choose to switch to buprenorphine over a slow taper down.

 Having the ability to offer this medication choice to veterans with chronic pain on LTOT, with or without a diagnosis of OUD, has been a game changer and has immediately and effectively lowered overall opioid safety risk.

Likelihood of benefit from switch to buprenorphine. Using our experience, we refer to the “Rule of Thirds.” One-third of patients prefer buprenorphine; they feel better, have fewer adverse effects, function at greater levels. One-third of patients see no appreciable analgesic benefit from buprenorphine, but neither are they worse, and the adverse effect profile is improved for many. In particular, some patients note they are “not thinking” about the next dose of opioids and like the long duration of action of the medication. One-third of patients have inadequate analgesia. For these patients, we encourage them to give buprenorphine a trial at adequate doses for 2 to 3 weeks and then, if the case does not merit an OUD diagnosis, we can consider a retrial of low-dose (less than 50 MME) full agonist opioid. Knowing this is a potential option provides an added layer of security, making it easier for patients to switch.

When discussing opioid reduction with patients, we suggest assuring them that good alternatives exist: “It’s clear from listening to you that pain is really controlling your life and keeping you from doing many of the things you enjoy. You are taking a high dose of opioid, and yet you are still experiencing a great deal of pain. You do not particularly like taking this medication and yet, the idea of tapering down leaves you wondering if the pain will get worse. You’re stuck. The good news is that I will work with you to get you on a safer and equally or even more effective regimen, as well as provide treatments that have significant evidence behind them.”

Once the decision has been made to switch to buprenorphine, there are a couple of methods to initiate buprenorphine for patients with chronic pain on opioids.

Buprenorphine formulations for chronic pain. When treating patients with chronic pain and without OUD, there are 2 FDA-approved formulations of buprenorphine. Buprenorphine doses for chronic pain are lower than those formulated to suppress OUD symptoms and stop non-prescribed use of opioids. For this reason, although it is acceptable to use formulations designed for OUD treatment off-label for chronic pain, prescribers should not use formulations for chronic pain in patients with OUD, as sufficient doses cannot be achieved to effectively prevent opioid craving. Buprenorphine for chronic moderate to severe pain comes in a transdermal patch and a buccal formulation. Consider the patch in patients on 20 to 80 MME; the buccal formulation should be considered with doses between 80 to 160 MME.

Buprenorphine formulations for OUD. There are several FDA-approved formulations for treating OUD including sublingual (SL), buccal, implants, and long-acting injectables. In general, with off-label use of buprenorphine formulated for OUD to manage chronic pain, preference is given to faster acting SL or buccal formulations. When used for OUD, buprenorphine is typically dosed once daily; when used off-label for pain, however, divided doses of buprenorphine may be preferable to provide greater analgesic coverage.

A common question arises: how best to initiate buprenorphine in people on LTOT? Historically, we have deployed the same method used to initiate buprenorphine in anyone with OUD currently using opioids—ie, stop the full agonist, wait for moderate opioid withdrawal, 

 However, in our experience, it is difficult to convince patients with chronic pain who have been prescribed LTOT and who are without OUD to agree to a switch once they hear they will have to initiate opioid withdrawal. Opioid withdrawal is accompanied with significant distress and worsening pain. Fear of opioid withdrawal often promotes continued use of LTOT long after analgesic benefit ceases. For this reason, we are increasingly using an overlap protocol that starts with very low doses of buprenorphine and increases slowly over days, while continuing the full agonist opioid. A recent case series was published looking at veterans on high-dose LTOT, with veterans transitioning from 300+ mg MME. 

 explains a typical home initiation protocol.

Getting back to our case example, how can we best help Ms Morris? Begin by reframing chronic pain as a complex interaction of earlier tissue damage, followed by central sensitization, and continued chronification driven by undertreated depression and physical inactivity/deconditioning. Dispel common misconceptions about chronic pain that can lead to a cycle of fear of exacerbating pain and further avoidance of activity. Also, initiate a behavioral activation plan along with realistic goal setting and identification of cognitive distortions related to the nature and meaning of pain. “Prescribe” a weekly yoga class, walking regimen, or phone call with a friend. Rather than focusing on decreased pain intensity as the goal of treatment, shift the therapeutic focus for Ms Morris to increased pain coping or pain functioning.

Treat mood with both nonpharmacologic and pharmacologic treatments, preferring treatments that might also target chronic pain. For Ms Morris, you might prescribe an SNRI. (The choice of SNRI will vary based on etiology of chronic pain, medical/psychiatric comorbidities, treatment history, and patient-specific factors such as age, weight, and so on. The factors that go into selecting an SNRI or TCA [tricyclic antidepressant] are beyond the scope of the paper.) You should discuss the potential utility of NSAIDs, analgesic patches, and acupuncture with the primary care doctor.

It is also important to negotiate a goal for reduced or alcohol use or abstinence. In Ms Morris’ case, she agrees to stop drinking altogether for the next month until her next visit. She agrees that alcohol use might be interfering with her mood and has noticed its effect upon sleep, which worsens her experience of pain. She will replace drinking with a casual evening walk.

You should also discuss the plan for her opioids and the unique place of buprenorphine. You might explain to Ms Morris that her current dose of opioid, despite a significant taper, is still high (135 mg MME) and offer her a constrained choice of continuing an opioid taper or switching to buprenorphine. It is likely she will choose to switch to buprenorphine SL, as off-label use of this formulation is currently more affordable than on-label buccal buprenorphine approved for pain. Remind her of the overlap protocol, since she is afraid to experience opioid withdrawal.

Psychiatrists and addiction specialists should be trained in the management of chronic pain and be willing and able to collaborate with pain specialists in the co-management of these patients. The time has arrived for psychiatrists to recognize and capitalize on our unique skill sets (diagnosing and treating substance use and co-occurring psychiatric disorders, including chronic pain conditions) and become strong partners in a collaborative care model of pain treatment.

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Articles

This CME will inform clinicians with unique and much-needed skill sets in diagnosing substance use disorders and managing co-occurring chronic pain.