ASRA Pain Medicine Update

In 2016, the U.S. Centers for Disease Control (CDC) issued its Guideline for Prescribing Opioids¹ and cautioned physicians and clinicians about starting new opioid prescriptions, as well as increasing the dose of existing opioid prescriptions. One year after it was published, national retail pharmacy data revealed that opioid prescribing had decreased by 57% each month in the United States over the preceding year.²

At their core, these rigid opioid dose policies violate the basic principles of patient-centered pain care while deeply undermining physician autonomy in medical decision-making for the individual patients they treat.

This same study showed that while decreased opioid prescribing preceded the 2016 CDC Guideline, the slope of prescribing decreased substantially afterward. Indeed, the guideline emboldened opioid reduction practices and policies in ways that its authors never intended. Since 2016, opioid prescribing decreases have been attributable to fewer new opioid prescriptions and the tapering of opioids among people who had been taking them long term. This last point is of particular relevance as the CDC Guideline included no language about opioid tapering indications or implementation.

However, some health care organizations and states have wrongly cited the 2016 CDC Guideline as a basis to substantiate prescribing “dose-based limits” or to mandate that physicians and prescribers taper patients taking long-term opioids to specific thresholds (eg, < 90 mg, or < 50 mg). Such dose-based opioid prescribing policies are neither supported by the CDC, nor do they account for the medical circumstances of the individual patient. At their core, these rigid opioid dose policies violate the basic principles of patient-centered pain care while deeply undermining physician autonomy in medical decision-making for the individual patients they treat.

Curiously, improving patient safety through opioid reduction is a primary justification cited for policies that mandate opioid tapering. Indeed, data suggest that higher doses of opioids are directly associated with risk for opioid overdose and overdose death. However, for many patients, the consequence of the misapplication of the CDC Guideline has been direct harm. Reports of iatrogenic tapering harms spurred colleagues and me to submit to U.S. Health and Human Services (HHS) a letter calling for federal action to protect patients from abrupt and forced opioid tapering harms (subsequently published in Pain Med³). I testified to the U.S. Congress twice and once to the U.S. Food and Drug Administration (FDA) on the underappreciated iatrogenic consequences of forced opioid tapering, the national need to deliver patient-centered pain care, and the need for protections for the vulnerable patient population of patients taking long-term prescription opioids. Human Rights Watch published a report documenting patient harms from forced opioid tapering.⁴  In response, the FDA issued a formal caution against the dangerous practice of abrupt opioid tapering.⁵ More than 300 health care professionals and three former U.S. Drug Czars who advised past presidents on national drug policy (Michael Botticelli, Jerome Jaffe, MD, and Barry McCaffrey, Ret. US General) called on the CDC to address the misapplication of the Opioid Guideline.⁶ The CDC laudably responded by issuing a clarifying statement that derided the misapplication of the opioid guideline and discouraged the dose-based policies and practices that fall outside of its scope, as well as use of the guideline to substantiate tapering.⁷

The CDC and HHS responded further with the 2019 publication of the first federal document to directly address opioid tapering implementation, the HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-Term Opioid Analgesics.⁸ The guidance focuses on individualized care, patient-centeredness, and a core philosophy that supports the clinician in treating the patient rather than their medication. Importantly, the document emphasized voluntary or consensual opioid reduction, encouraged very close monitoring during tapering, and methods that emphasize patient safety during and after a taper as primary. For instance, the HHS document “does not suggest discontinuation of opioids” for patients taking high-dose opioids, and instead indicates that health care clinicians should “collaborate with patients who agree to taper their dose.” Furthermore, HHS acknowledged that opioids are beneficial for some patients, prescribing autonomy should be preserved, and poor response to a taper may be indicative of opioid benefits. Like all medical care, opioid tapering decisions should be based on the individual patient response; as such, opioid tapers should not be mandated as unidirectional.

In the intervening timeframe, we have seen a host of studies suggest that opioid tapering can introduce many iatrogenic health risks, including opioid overdose,⁹ increased pain, suicidality, and suicide.¹⁰ A pervasive notion that reducing opioids uniformly confers health benefits is unsupported. Data suggest that opioid dose changes, in either direction, confer health risks to the patient.⁹ In short, efforts to correct opioid prescribing health risks should not introduce new risks to the broader population; this is one issue to be tackled by the authors of the upcoming revision and new national guidance on opioid prescribing.

The CDC is in the beginning stages of updating the 2016 Opioid Prescribing Guideline. In December 2019 the creation of the Opioid Workgroup was approved by the Board of Scientific Counselors of the National Center for Injury Prevention and Control (BSC/NCIPC). The primary purpose of the opioid workgroup is to review evidence, draft updates to the guideline for prescribing opioids and to develop a report that will provide the Opioid Workgroup's findings and observations about the draft guideline to the BSC/NCIPC. The full roster of the Opioid Workgroup may be viewed here, and I am pleased to be included. Importantly, the roster includes a range of stakeholders, including advocacy and patient representatives.

The CDC issued a federal docket (CDC-2020-0029) requesting public and stakeholder opinions on revising the 2016 Opioid Prescribing Guideline. The American Medical Association responded and noted that “many health insurance plans and pharmacy benefit managers have used to the 2016 CDC Guidelines to justify inappropriate one-size-fits-all restrictions on opioid analgesics while also maintaining restricted access to other therapies for pain.”¹¹  The AMA docket response cited the American Board of Pain Medicine survey which found that:

• 72% of pain medicine specialists said that they—or their patients—have been required to reduce the quantity or dose of medication they have prescribed;
• 92% of pain medicine specialists said that they have been required to submit a prior authorization for non-opioid pain care—with the physicians and their staff spending hours per day on such requests; and
• 66% of pain medicine specialists said that they have had to hire additional staff to handle the prior authorization requirements.

The letter cites that the misapplication of the CDC Guideline, coupled with additional barriers to pain care, have undermined best practices for pain care and require correction with a focus on improved pain care.

To be clear, we need better evidence on how to best implement opioid tapering. Our research group has focused on voluntary patient-centered opioid tapering with positive early results and long-term results.^12-13 We are now conducting a four-state voluntary patient-centered opioid tapering study that is funded by the Patient-Centered Outcomes Research Institute (PCORI).¹⁴ The study is called Effective Management of Pain and Opioid-Free Ways to Enhance Relief (EMPOWER¹⁵). The EMPOWER study emphasizes patient choice for participation, pace of the taper, taper goals, and the taper dose result at one year. Our program emphasizes managing patient symptoms, addressing patient needs, and collecting weekly status reports from patients to inform their treatment needs and to ensure we collect high quality on the patient experience during opioid tapering. The ultimate goal is to help people achieve their lowest comfortable opioid dose over one year. We are also testing the comparative effectiveness study of two evidence-based behavioral medicine treatments to support patient outcomes for opioid and pain reduction, compared to people who receive only the taper and no behavioral support. The EMPOWER study recognizes that not all patients can or should taper opioids:  a fraction of patients need opioids as one part of a comprehensive pain care plan to address complex medical conditions and analgesic needs. Patients whose pain is best managed with opioids should not face additional stigma, burdens and barriers to care, or receive labeling along the continuum of an addictive disorder.

While many unknowns remain, the development of the CDC Opioid Workgroup, coupled with the CDC dockets soliciting public and stakeholder feedback on needed changes to the 2016 Opioid Guidelines are highly promising. The CDC has acknowledged the unintended consequences of the Guideline in its 2019 correction, the 2019 HHS tapering guidance, and in public meetings. The hope is that the upcoming efforts, and a CDC opioid prescribing guideline revision in 2021 or 2022, will place the patient at the center of pain care in the U.S., restore autonomy to prescribing physicians and clinicians, and allow direct scientific evidence to drive future opioid policies and clinical recommendations.

Beth Darnall, PhD, is an associate professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University School of Medicine, and is Director of the Stanford Pain Relief Innovations Lab. She leads research on patient-centered opioid reduction and behavioral medicine for acute and chronic pain. In 2020 she was appointed to the CDC Opioid Workgroup. Twitter:  @bethdarnall

References

1. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR Recomm Rep. 2016;65(No. RR-1):1–49.
2. Bohnert ASB, Guy GP, Jr., Losby JL. Opioid prescribing in the United States before and after the Centers for Disease Control and Prevention's 2016 opioid guideline. Ann Intern Med. 2018;169(6):367-75.
3. Darnall BD, Juurlink D, Kerns RD, et al. International stakeholder community of pain experts and leaders call for an urgent action on forced opioid tapering. Pain Med. 2018;20(3):429–33. https://doi.org/10.1093/pm/pny228 
4. Human Rights Watch. Not allowed to be compassionate: chronic pain, the overdose crisis, and unintended harms in the US. 2018. Available at: https://www.hrw.org/report/2018/12/18/not-allowed-be-compassionate/chronic-pain-overdose-crisis-and-unintended-harms-us#. Accessed January 27, 2019.
5. U.S. Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering: FDA Drug Safety Communication. 2019. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-identifies-harm-reported-sudden-discontinuation-opioid-pain-medicines-and-requires-label-changes.
6. Health Professionals for Patients in Pain. Health Professionals Call on the CDC to Address Misapplication of its Guideline on Opioids for Chronic Pain through Public Clarification and Impact Evaluation. Available at: https://healthprofessionalsforpatientsinpain.org/the-letter-1. 2019.
7. Dowell D, Haegerich T, Chou R. No shortcuts to safer opioid prescribing. N Engl J Med. 2019; 380:2285-7. https://doi.org/10.1056/NEJMp1904190. 
8. Dowell D, Compton WM, Giroir BP. Patient-centered reduction or discontinuation of long-term opioid analgesics: the HHS guide for clinicians. JAMA. 2019:1-3.
9. Glanz JM, Binswanger IA, Shetterly SM, Narwaney KJ, Xu S. Association between opioid dose variability and opioid overdose among adults prescribed long-term opioid therapy. JAMA Netw Open. 2019;2(4):e192613.
10. Oliva EM, Bowe T, Manhapra A, et al. Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation. BMJ. 2020;368:m283.
11. American Medical Association. AMA response letter to CDC (Docket No. CDC-2020-0029). Available at: https://searchlf.ama-assn.org/undefined/documentDownload?uri=%2Funstructured%2Fbinary%2Fletter%2FLETTERS%2F2020-6-16-Letter-to-Dowell-re-Opioid-Rx-Guideline.pdf2020.
12. Darnall BD, Ziadni MS, Stieg RL, Mackey IG, Kao MC, Flood P. Patient-centered prescription opioid tapering in community outpatients with chronic pain. JAMA Intern Med. 2018;178(5):707-8.
13. Ziadni MS, Chen A, Krishnamurthy P, Flood P, Stieg RL, Darnall BD. Patient-Centered Prescription Opioid Tapering in Community Outpatients with Chronic Pain:  2- to 3-year follow-up in a subset of patients. PAIN Reports®: September/October 2020 - Volume 5 - Issue 5 - p e851. http://doi.org.10.1097/PR9.0000000000000851
14. BD, Mackey, SC, Lorig K, et al. Comparative effectiveness of cognitive behavioral therapy for chronic pain and chronic pain self-management within the context of voluntary patient-centered prescription opioid tapering: the EMPOWER study protocol. Pain Med. 2019;21(8)1523-31. https://doi.org/10.1093/pm/pnz285. 
15. Stanford University. EMPOWER study: effective management of pain and opioid-free ways to enhance relief. Available at: https://empower.stanford.edu/.  Accessed August 1, 2020.