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Andre Chen, MD

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About Andre Chen, MD

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  • Birthday 10/16/1966

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  1. A related clinical situation would be that of a low-dose chronic pain patient who has tested positive for an substance such as THC or non-prescribed medication and has been deemed to be too high risk to continue chronic pain management with traditional opioids. The risk may be to the patient or to the prescriber. This recent article Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion includes the following as possible reasons one could consider the use of buprenorphine for pain. Concern from health care providers regarding prescription of a Schedule II opioid due to risk of addiction, misuse, and/or overdose death A patient is receiving immediate-release treatment and would benefit from a longer-acting analgesic with a relatively favorable safety profile and Schedule III classification It would not be unusual for a patient to minimize any difficulties they may be having with their short-acting opioid regimen and for family and friends to be more aware of the behavioral problems. I would suspect that there is more of a problem than what the patient is willing to admit to given that they agreed to see you. A longer-acting analgesic may reduce the problems seen with the highs and lows of opioid effect such as cognitive efffects immediately after dosing and the relative withdrawal feeling prior to the next dose. In this instance, due to the low daily dose, the buprenorphine formulations typically used for pain, Butrans or Belbuca, may be more appropriate as a patient on 22.5 MME/day would likely require less than 2mg of buprenorphine SL per day.
  2. This good review article is open access so I attached it here. Gudin-Fudin2020_Article_ANarrativePharmacologicalRevie.pdf
  3. Attached are some very recent articles referencing the use of buprenorphine for pain. They are at the expert opinion level but from reputable sources. Also, some text referencing buprenorphine for pain in the Official Disability Guidelines and the HHS Pain Management Task Force Report ====================================================== ODG Pain (updated 7/26/2019) Buprenorphine for chronic pain Recommended as an option for treatment of chronic pain (consensus based) in selected patients (not first-line for all patients). See also Buprenorphine for treatment of opioid dependence. Suggested populations: (1) Patients with a hyperalgesic component to pain; (2) Patients with centrally mediated pain; (3) Patients with neuropathic pain; (4) Patients at high-risk of non-adherence with standard opioid maintenance; (5) For analgesia in patients who have previously been detoxified from other high-dose opioids. Use for pain with formulations other than Butrans is off-label. Due to complexity of induction and treatment the drug should be reserved for use by clinicians with experience. Drug description: Buprenorphine is a schedule-III controlled substance. Its mechanism of action is complex, involving four different opioid receptors at central and peripheral sites. It is primarily classified as a partial mu-agonist and kappa antagonist. It blocks effects of subsequently administered opioid agonists. Proposed advantages of treatment: (1) An apparent antihyperalgesic effect (partially due to the effect at the kappa-receptor); (2) Ability to suppress opioid withdrawal; (3) Indications of safety for use in patients with renal impairment. There appears to be a ceiling effect for respiratory depression. (Johnson, 2005) (Kopper-t, 2005) (Pergolizzi, 2008) (Malinoff, 2005) (Landau, 2007) (Kress, 2008) (Heit, 2008) (Helm, 2008) (Silverman, 2009) (Pergolizzi, 2010) (Lee, 2011) (Rosenblum, 2012) (Daitch, 2012) (Colson, 2012) See also Opioid hyperalgesia. Treatment of chronic pain: A waiver is not required for the off-label use of sublingual buprenorphine for the treatment of pain. An X should NOT be put before the DEA number. It is recommended that the words, Chronic Pain Patient and Off-Label Use be written on the prescription. The most common use of buprenorphine formulations other than Butrans (such as Suboxone) for the treatment of chronic pain is for individuals who have a history of opioid addiction. Use in opioid-experienced patient: There is the potential for buprenorphine to precipitate withdrawal in opioid-experienced patients. ======================================================== PAIN MANAGEMENT BEST PRACTICES INTER-AGENCY TASK FORCE REPORT Updates, Gaps, Inconsistencies, and Recommendations PAIN MANAGEMENT FINAL REPORT Buprenorphine, an opioid medication that the FDA has approved for clinical use, is a partial agonist at the mu opioid receptor and therefore has a reduced potential for respiratory depression; it is thus safer than full agonists such as morphine, hydrocodone, and oxycodone.120,121 Buprenorphine also acts as an antagonist at the kappa receptor, an effect shown in experimental studies to reduce anxiety, depression, and the unpleasantness of opioid withdrawal. Buprenorphine is widely used and encouraged for treating patients with OUD and is approved for the treatment of pain. In some states, there is a significant challenge, however, for prescribing clinicians to get authorization for using buprenorphine for chronic pain management (see Section 2.2: Medication, Gap 4 and Recommendations). GAP 4: Barriers include lack of coverage and reimbursement for buprenorphine as well as the lack of education and training on the proper usage of buprenorphine. There has been a lack of access to buprenorphine treatment for chronic pain.143 • RECOMMENDATION 4A: Make buprenorphine treatment for chronic pain available for specific groups of patients, and include buprenorphine in third-party payer and hospital formularies. • RECOMMENDATION 4B: Encourage CMS and private payers to provide coverage and reimbursement for buprenorphine treatment, both for OUD and for chronic pain. Encourage primary use of buprenorphine rather than use only after failure of standard mu agonist opioids such as hydrocodone or fentanyl, if clinically indicated. • RECOMMENDATION 4C: Encourage clinical trials using buprenorphine for chronic pain to better understand indication, usage, and dosage. ----------------------------------------------- 2.5.2 Patients With Chronic Pain as well as Mental Health and Substance Use Comorbidities GAPS AND RECOMMENDATIONS GAP 1: CBPs for chronic pain do not adequately address how to treat individuals with comorbid psychological health concerns. • RECOMMENDATION 1A: Screen for psychological health and SUDs in patients with acute or chronic pain, and consider early referral to behavioral health providers when clinically indicated. • RECOMMENDATION 1B: Use an integrated multidisciplinary approach that may include existing evidence-based psychological and behavioral interventions (e.g., CBT, coping skills, stress reduction, mindfulness-oriented recovery) to address chronic pain when clinically indicated. • RECOMMENDATION 1C: Refer patients to both pain and addiction specialists when OUD is suspected, and ensure an integrative approach to health care. • RECOMMENDATION 1D: Buprenorphine may be considered appropriate for pain treatment in this population when clinically indicated. • RECOMMENDATION 1E: When considering buprenorphine and other opioids, use the lowest effective dose in conjunction with non-opioid treatment modalities, with enhanced monitoring and collaboration with addiction specialists. Conduct regular reevaluation and assessment, with a treatment plan and established goals, to achieve optimal patient outcomes. Webster - Bup for Pain.pdf Yale_bup.pdf Rethinking Opioid Dose Tapering.pdf
  4. I believe these are studies of Veterans Administration data done by Canadian statisticians. The individual studies are listed by primary author but I'm not sure who put them all together on this chart as it came from a presentation given about two years ago. I like it because it nicely shows where the 50 MME and 90 MME cutoff points may have come from. All too often, I'm showing this to a patient and pointing out that their daily dose far exceeds what is on this chart.
  5. Oxycodone 10 mg four times per day is 60 MME so 16-24 mg of bup per day sounds somewhat high, to me, as a target dose. There are no real established guidelines about how to transition patients from Schedule 2 opioids for pain, however, this is something that I do on a daily basis in my practice. What I would do is stop the oxycodone for 12 to 24 hours. Then bup/nalox 2mg tab or film 1/2 sl bid for two days; 1/2 sl tid for 2 days; then 1/2 sl qid after that. Target dose of 4 mg per day. My general formula for this kind of conversion is 1 mg bup for every 10 MME MINUS 30-50% for incomplete cross tolerance. Something I still have a hard time comprehending is the incredible gab between pain management dosing of buprenorphine which is usually less than 2 mg per day and dosing for OUD at up to 24 mg per day.
  6. There are significant problems with using buprenorphine for post-op pain control. The long half life means that it it takes days to reach steady state. As a long-acting opioid, all but the lowest-dose formulations (Belbuca 75ug q12h and Butrans 5ug/hr) would be contraindicated in opioid-naive patients. Since most guidelines and some states and health plans actually mandate post-op regimens for opioid-naive patients be limited to 3-7 days, such a long-acting opioid would likely not be suitable in most cases.
  7. I often print this article for patients in brochure form and hand it to patients (attached PDF). It's two sheets of paper folded in half to make a six-page booklet. https://www.verywellhealth.com/buprenorphine-for-chronic-pain-management-4156472 Using Buprenorphine for Chronic Pain Management Is buprenorphine the future of chronic pain treatment? By Naveed Saleh, MD, MS Updated May 22, 2018 At face value, the opioid crisis and chronic pain are directly opposed. Although the CDC points out that “evidence on long-term opioid therapy for chronic pain outside of end-of-life care remains limited, with insufficient evidence to determine long-term benefits versus no opioid therapy,” the fact remains that opioids are the principal intervention for the treatment of chronic pain. Although primary care providers can prescribe opioids for chronic pain, they are reluctant to do so for fear of patient overdose or dependence. Most primary care physicians find the prospect of giving patients opioids for a long period of time too stressful and quickly refer these patients to pain specialists. Despite reluctance to treat it, chronic pain is becoming increasingly frequent. In 2010, 31 percent of Americans experienced chronic pain, which is defined as pain lasting more than three to six months. Because the vast majority of people with chronic pain present to primary care physicians, it would be a breakthrough if we had some safe and effective alternative to opioids—some medication that these physicians would feel comfortable prescribing. A medication called buprenorphine may someday help fit this bill. What Is Buprenorphine? Buprenorphine belongs to a class of drugs called opioid partial agonist-antagonists. In addition to another drug which combines buprenorphine and naloxone (Suboxone), buprenorphine is used as opioid substitution therapy to treat opioid dependence (dependence on heroin or prescription narcotics). These drugs work by preventing withdrawal symptoms when a person who is dependent on opioids stops taking opioids. Buprenorphine is a semisynthetic opioid derivative of the opium alkaloid thebaine, which is found in the opium poppy (Papaver somniferum). It actually took decades for researchers to synthesize the drug, and there were many failed attempts before an English pharmaceutical company finally made it in 1966. By 1978, an intravenous formulation of buprenorphine was introduced, followed by a sublingual (applied under the tongue) iteration in 1982. In 1985, buprenorphine was introduced in the United States as an opioid analgesic. How It Works Buprenorphine has very specific mechanisms of action that make it enviable not only for treating opioid dependence but possibly chronic pain, too. First, buprenorphine has a high binding affinity for the μ-opioid receptor, which is responsible for pain relief. Moreover, buprenorphine has a slow rate of dissociation from the μ-opioid receptor, meaning that it stays attached longer to the receptor, and has prolonged effect. Second, although buprenorphine likes the μ-opioid receptor quite a bit, it acts only as a partial μ-opioid receptor agonist, which means that while buprenorphine prevents opioid withdrawal, its actions are less potent than opioids. Third, buprenorphine is a full κ-opioid receptor antagonist. Activation of the κ-opioid receptor results in the euphoric and psychotic effects of opioids. In other words, buprenorphine won’t make you “high.” Administration As mentioned earlier, naloxone is often combined with buprenorphine in the form of Suboxone. Naloxone is a short-acting, opioid receptor antagonist. When combined in low doses with buprenorphine, naloxone can counteract dangerous opioid side effects—including respiratory depression, sedation, and hypotension—without diminishing analgesia, or pain relief. Furthermore, the addition of naloxone to buprenorphine serves as a deterrent to substance abuse. According to the NIH: "Buprenorphine comes as a sublingual tablet. The combination of buprenorphine and naloxone comes as a sublingual tablet (Zubsolv) and as a sublingual film (Suboxone) to take under the tongue and as a buccal [cheek] film (Bunavail) to apply between the gum and cheek." Buprenorphine also comes in a transdermal patch, intravenous formulation, and, most recently, a sublingual spray. In December 2017, it was announced that the FDA was reviewing the new sublingual spray for treatment of acute pain. Side Effects Although not nearly as dangerous as opioids, both buprenorphine and Suboxone can have negative side effects including the following: Back pain Blurred vision Constipation Difficulty with sleep Mouth numbness Headache Stomach pain Tongue pain More serious side effects, such as difficulty breathing or swelling of the mouth or tongue, require immediate medical attention. Importantly, mixing buprenorphine with other drugs like benzodiazepines can be lethal. Buprenorphine for Chronic Pain In a systematic review published in December 2017, Aiyer and co-authors examined the efficacy of buprenorphine for the management of chronic pain. The researchers analyzed 25 randomized controlled trials involving five buprenorphine formulations: Intravenous buprenorphine Sublingual buprenorphine Sublingual buprenorphine/naloxone (Suboxone) Buccal buprenorphine Transdermal buprenorphine Overall, the researchers found that 14 of 25 studies suggested that buprenorphine in any formulation was effective for the treatment of chronic pain. More specifically, 10 of 15 studies showed that transdermal buprenorphine was effective, and two of three studies showed that buccal buprenorphine was effective. Only one of six studies indicated that either sublingual or intravenous buprenorphine was effective for the treatment of chronic pain. Importantly, no serious adverse effects were reported in any of the studies, which indicates that buprenorphine is safe. In 2014, Cote and co-authors published a systematic review examining the efficacy of sublingual buprenorphine for the treatment of chronic pain. Although the majority of studies they analyzed were observational and low-quality, the researchers did find that sublingual buprenorphine was effective at treating chronic pain. Notably, Cote and co-authors compiled the following list of potential benefits of buprenorphine: Increased efficacy in neuropathic pain due to its unique pharmacological profile. Ease of use in the elderly and in renal impairment due to its minimal effect on half-life and metabolites. Less immunosuppression compared with morphine and fentanyl based on very limited evidence from preclinical and clinical work. Ceiling effect for respiratory depression when used without other central nervous system depressants, perhaps because the intrinsic activity to produce analgesia may be less than that of respiratory depression. Less effect on hypogonadism, as demonstrated in maintenance therapy. Less development of tolerance, possibly through kappa receptor antagonism or opioid-receptor-like (ORL-1) agonism. Antihyperalgesic effect, perhaps due to kappa receptor antagonism or ORL-1 agonism. Antidepressant effect in patients unresponsive to conventional therapy. Interestingly, it’s hypothesized that because of its binding properties, buprenorphine may be able to help people who experience opioid-induced hyperalgesia. In an article titled “A comprehensive review of opioid-induced hyperalgesia,” Lee and co-authors opioid-induced hyperlagesia as the following: "Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients." Of note, nociceptive pain is the sharp pain resulting from damage to a body part. It’s hypothesized that buprenorphine has antinociceptive properties. In a 2014 article published in Anesthesiology, Chen and co-authors write the following: "Buprenorphine has been shown to reverse hyperalgesia induced by opioids through ‘buprenorphine-induced antinociception.’ Moreover, buprenorphine is a κ-receptor antagonist and can compete with the effect of spinal dynorphin, an endogenous κ-receptor agonist. Because spinal dynorphin is increased after opioid exposure and contributes to OIH, this competitive effect of buprenorphine on the κ-receptor binding site may decrease the effect of spinal dynorphin resulting in the decreased OIH." Prescribing Buprenorphine To a limited extent, in the United States, buprenorphine is already being used to treat chronic pain. Suboxone is prescribed off-label for the treatment of chronic pain. Furthermore, the transdermal buprenorphine patch is available for the treatment of severe chronic pain in the United States. However, there is no consensus opinion with regard to the efficacy of using buprenorphine for this purpose. Currently, the few studies examining the effect of buprenorphine on chronic pain are too disparate in their approaches, and are thus too difficult to compare with one another. Before the prescription of buprenorphine for the treatment of chronic pain becomes an evidence-based practice, various issues would need to be resolved. For example, current studies use a variety of pain rating scales when evaluating efficacy thus providing an inconsistent analysis. Pain rating scales in studies examining buprenorphine would need to be standardized. Furthermore, dosing strategies and route of administration would need to be examined for different presentations of chronic pain. If the prescription of buprenorphine for chronic pain were ever to become evidence-based, primary care physicians would ostensibly be primed for this practice. In 2000, the U.S. Drug Addiction Treatment Act made it legal for primary care physicians to provide opioid substitution therapy using Schedule III, IV, and V drugs. In 2002, the FDA approved out-patient treatment with buprenorphine, characterizing it as a Schedule III drug. All that a primary care physician needs to do to be able to prescribe buprenorphine in an out-patient setting is to complete eight hours of training. Nevertheless, few primary care providers have become eligible to prescribe buprenorphine. Although many primary care physicians would likely bristle at the suggestion, it wouldn’t be that big of a stretch to think that primary care physicians could someday treat chronic pain in the outpatient setting using buprenorphine. In addition to primary care physicians having the ability to prescribe buprenorphine, the CDC also has guidelines in place for primary care physicians to treat chronic pain with opioids. Essentially, the CDC guidelines recommend that primary care physicians prescribe opioids for chronic pain only when non-opioid treatments are not sufficient, and to prescribe opioids at the lowest dose possible. In this context, buprenorphine could essentially be considered an opioid alternative. Bup Chronic Pain.pdf
  8. I have found the attached commentary by Ajay Manhapra, MD useful in defining a syndrome that represents more than dependence but short of addiction - complex persistent dependence. Utilizing this approach, a patient can have clinically significant opioid dependence without opioid use disorder. Complex persistent dependence, the gray area between dependence and addiction A clear diagnostic dichotomy of OUD versus no OUD dictating discrete management pathways would be optimal, especially for primary care physicians trying to triage care in patients with complex pain on LTOT. However, as elegantly pointed out by Ballantyne et al., a diagnostic distinction between dependence and addiction is nearly impossible in many patients on LTOT with the available criteria,20 creating a diagnostic and therapeutic orphan status for these patients, somewhere in the gray area between the clear demarcations of simple dependence and frank addiction.24 Ballantyne et al.20,24 put forth the term “complex persistent dependence” (CPD) to describe the physiological and clinical state that exists in this gray area. Clinically significant CPD can be recognized as a patient’s desire to continue or increase the dose of LTOT, or inability to discontinue LTOT despite a prescriber’s recommendation to discontinue it. The symptoms of CPD include worsening pain, function, affective symptoms and sleep disturbance, affective dynamism with escalating opioid need while maintained on LTOT, and protracted withdrawal syndrome on opioid dose reduction or cessation. Based on typological classification and description of primary care patients with chronic pain on LTOT,2 it is reasonable to hypothesize that having !100 MMED opioid dose and/or significant pain dysfunction, aberrancies and misuse, psychiatric burden, and prior history of or active SUD offers an easy cutoff for primary care providers (PCPs) to identify these difficult-to-manage patients with high likelihood of CPD that may cause significant persistent adverse effects with opioid dose tapering. Real-life experiences suggested that attempt at opioid taper is difficult in patients with chronic pain and high opioid doses.4 These patients may have little insight into the role opioids are playing in their current state and thus may have little motivation and significant fear related to making a change. There is also grand rounds lecture on YouTube: Manhapra CPD.pdf
  9. Some approaches that I have seen experts in this area take: De-emphasizing the DSM5 criteria for patients in chronic pain and, instead, focus on whether the patient might benefit from a change in treatment plan. Practical Pain Management: Managing Opioid Use Disorders and Chronic Pain Liberalizing the diagnosis of OUD in chronic pain patients who are not doing well with opiates and treating accordingly. Adopting concepts like "Complex Dependence" COMMON THREADS IN PAIN AND CHEMICAL DEPENDENCY All of these approaches seem to de-emphasize the specific diagnosis or label of opioid use disorder in chronic pain patients as a distinction without a difference. The last link is a nearly three hour recording of last year's PainWeek pre-conference on Pain and Addiction which also can be accessed via a podcast app on your smartphone by searching for "PAINWeek"
  10. IThe California Health Care Foundation has a webinar and a very informative .pdf on the subject of buprenorphine and pain. If you YouTube “buprenorphine for pain,” you will see several interesting and practical lectures by Dr. Corey Waller on this exact subject. http://www.chcf.org/events/2016/webinar-opioid-safety-coalitions-buprenorphine PDF BuprenorphineFAQ.pdf
  11. The CDC Guidelines for Prescribing Opioids for Chronic Pain include the following: 8. Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use, are present (recommendation category: A, evidence type: 4). Given that is applies to about 90% of patients who are in pain management, what are some of the strategies that are employed in the setting of a pain management practice regarding distribution of naloxone rescue kits? Specifically: The use of a standing order at an in-house or local retail pharmacies. Direct distribution of "compounded" kits using syringes and an atomizer. Charging patients or billing insurance for these kits. Prescribing $4000 branded auto-injectors. Getting retail pharmacies to even fill the naloxone prescriptions without calling back about interactions with pain meds, available dosing forms, instructions, etc.
  12. The April 2017 update of the CDC's Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors increases the Buprenorphine film/tablet conversion factor from the previous 10 to 30 with the following footnote: "Buprenorphine formulations with a FDA approved indication for Medication Assisted Treatment (MAT) are excluded from Medicare’s Overutilization Monitoring System’s opioid overutilization reporting." Although it's somewhat reassuring that buprenorphine for MAT isn't subject to over utilization monitoring, there is no other explanation for the significant increase. The PMP system in my state, AwareRx, uses the 30 conversion factor so that anyone taking 8mg of buprenorphine a day, for pain, is listed at 240 MME/day which is sure to eventually set off the automated overprescribing alarms that will inevitably put in place to reduce opioid dosing. I find it had to believe that a patient taking six norco 10s per day is going to get similar pain relief from 2 mg of sl buprenorphine per day. My question is where did the change come from and whether it was based on clinical data or not? What's the consensus, here, about whether the conversion factor is closer to 10 or 30? Should we consider this to be non-linear relationship like we do with methadone? I'm concerned that we are soon going to be asked to justify prescribing 4 mg of sl buprenorphine per day for pain because that will be over 100 MME/day. Opioid-Morphine-EQ-Conversion-Factors-April-2017.pdf
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