The report is a product of the VA/HSR Evidence Synthesis Program.

Benefits and Harms of Long-term Opioid Dose Reduction or Discontinuation in Patients with Chronic Pain

In response to the evolving public health crisis related to opioid use, many providers, health systems, and payers are changing their approach to opioid prescribing for patients with chronic pain. The Centers for Disease Control & Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain and the 2017 VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain recommend using the lowest effective opioid doses for chronic pain – and considering dose reduction when opioid risks exceed benefits. Patients with chronic pain currently on long-term opioid therapy (LTOT) and the providers who care for them are at the center of a difficult balance between two necessary roles of the healthcare system: reducing suffering due to chronic pain, and reducing harms associated with opioid use. Maintaining this balance not only requires providers to consider the risks and benefits of LTOT, but also the potential risks and benefits of the tapering process itself. Given the urgent need for continued action to reduce opioid overdose deaths and other potential harms associated with long-term opioid use, improved understanding of patient outcomes following opioid tapers is necessary to inform best practices. The aim of this Evidence Brief was to synthesize findings from studies on tapering opioid prescribing for a broad range of outcomes, including pain severity and function and harms such as overdose and suicide, with an emphasis on the evidence most relevant and applicable to VA patient populations.

Investigators with VA’s Evidence Synthesis Program in Portland, OR searched MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase from January 1, 2017 through March 15, 2019; additional citations were identified from hand-searching reference lists and consultation with content experts. This Evidence Brief includes 34 of 40 studies from the Frank et al systematic review, as well as 10 new studies for a total of 44 primary studies – 5 randomized controlled trials (RCTs), 6 controlled observational studies, and 33 uncontrolled observational studies. After prioritizing studies that would be the most highly applicable and informative for VA (i.e., studies conducted in VA settings, and studies that evaluated serious harms of tapering, including suicide and overdose), investigators synthesized evidence from 15 studies for the following findings.

Summary of Findings

This review found that evidence is inadequate to fully weigh the balance of the benefits and harms of LTOT against the benefits and harms of tapering, primarily due to limited information on tapering harms. Additional findings include:

• For patients with chronic pain on LTOT who are concerned about worsening pain with tapers, evidence suggests that patients participating in intensive pain management interventions that incorporate opioid tapering may experience improvements in pain severity and pain-related function and that patients who taper opioids with less intensive co-interventions may have unchanged pain severity and pain-related function. However, given that these results are based on average changes in pain severity and function scores, clarity is still lacking in regard to how often LTOT tapers lead to rebound pain necessitating a change in management. Confidence in these findings is low, and additional evidence is needed before drawing stronger conclusions.
• Findings are inconclusive for other patient outcomes following opioid tapers, including serious harms such as overdose and suicide, as these outcomes have not been sufficiently studied. Close monitoring of patients during and after LTOT tapers given the potential for harms including overdose and suicide is therefore warranted. Special caution is needed for VA patients with PTSD and psychotic disorders, who may be at higher risk of suicidal ideation and suicidal self-directed violence following LTOT tapers.
• Very limited evidence is available to address the question of whether benefits and harms of opioid dose reduction or discontinuation vary by different patient characteristics or taper approaches. The most informative evidence on the role of different tapering approaches on outcomes comes from a retrospective study finding that rapid tapers (<3 weeks) are associated with increased emergency department visits and hospitalizations due to opioid-related adverse events than slower tapers.

Policy Implications

Although evidence suggests that many patients will tolerate a taper in terms of pain and pain-related function, the impact of LTOT tapers on serious harms, including overdose and suicide, is unclear, as few studies have evaluated these outcomes. Specifically, it is known that a subset of patients with chronic pain on LTOT have underlying opioid use disorder (OUD), but it is not known how often tapering interventions that “unmask OUD” lead to substance use or overdose – or how to mitigate these risks. Similarly, evidence suggests that VA patients with PTSD and psychotic disorder are at increased risk of suicidal ideation and suicidal self-directed violence following LTOT tapers, but additional specific risk factors for suicide following LTOT tapers have not been identified. Therefore, evidence does not rule out the possibility that broadly implemented health system- or clinician-initiated tapers may expose some patients to serious harms.

Limitations

Studies in this Evidence Brief had several limitations, such as inherent risk of bias associated with observational study designs (due to potential unmeasured confounders), lack of control groups in several studies, unclear fidelity to interventions, and inadequate reporting and/or handling of missing data. Despite these limitations, within the subset of studies with the most VHA applicability, findings regarding pain and pain-related function were consistent.

Future Research

The findings of this review highlight important evidence gaps in the following areas:

• Rates of serious adverse events associated with LTOT tapers including opioid overdose, suicidal ideation, and suicidal self-directed violence, as well as patient and intervention characteristics associated with these risks.
• Rates of newly diagnosed OUD during LTOT tapers, prevalence of “complex persistent opioid dependence” and criteria distinguishing this diagnosis from OUD, and the percentage of patients who are referred to substance use treatment.
• Association of baseline substance use disorders and mental health diagnoses with LTOT outcomes.
• Specific patient and intervention characteristics associated with improved pain and function following opioid tapers, including how outcomes differ between voluntary/patient-initiated tapers and mandated tapers – and by opioid regimen.

Mackey K, Anderson J, Bourne D, Chen E, Peterson K. Evidence Brief: Benefits and Harms of Long-term Opioid Dose Reduction or Discontinuation in Patients with Chronic Pain. Washington, DC: Evidence Synthesis Program, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-199; 2019.

To view the full report, go to http://www.hsrd.research.va.gov/publications/esp/tapering-opioid.cfm

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR&D's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers –; and to disseminate these reports throughout VA.

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