Ensuring Patient Protections When Tapering Opioids

CONSENSUS RECOMMENDATION

Ensuring Patient Protections When TaperingOpioids: Consensus PanelRecommendationsEdward C. Covington, MD; Charles E. Argoff, MD; Jane C. Ballantyne, MD;Penney Cowan; Halena M. Gazelka, MD; W. Michael Hooten, MD;Stefan G. Kertesz, MD, MSc; Ajay Manhapra, MD; Jennifer L. Murphy, PhD;Steven P. Stanos, Jr, DO; and Mark D. Sullivan, MD, PhD

Abstract

Long-term opioid therapy has the potential for serious adverse outcomes and is often used in avulnerable population. Because adverse effects or failure to maintain benefits is common with long-term use, opioid taper or discontinuation may be indicated in certain patients. Concerns about theadverse individual and population effects of opioids have led to numerous strategies aimed at re-ductions in prescribing. Although opioid reduction efforts have had generally beneficial effects, therehave been unintended consequences. Abrupt reduction or discontinuation has been associated withharms that include serious withdrawal symptoms, psychological distress, self-medicating with illicitsubstances, uncontrolled pain, and suicide. Key questions remain about when and how to safelyreduce or discontinue opioids in different patient populations. Thus, health care professionals whoreduce or discontinue long-term opioid therapy require a clear understanding of the associatedbenefits and risks as well as guidance on the best practices for safe and effective opioid reduction. Aninterdisciplinary panel of pain clinicians and one patient advocate formulated recommendations ontapering methods and ongoing pain management in primary care with emphasis on patient-centered,integrated, comprehensive treatment models employing a biopsychosocial perspective.

ª 2020 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2020;95(10):2155-2171

From the NeurologicalCenter for Pain (Emer-itus), Cleveland Clinic,Cleveland, OH (E.C.C.);Comprehensive PainCenter, Albany MedicalCollege, Albany, NY(C.E.A.); Department ofAnesthesiology and PainMedicine, University ofWashington, Seattle(J.C.B.); American ChronicPain Association, Rocklin,CA (P.C.); Department ofAnesthesiology and Peri-operative Medicine, MayoClinic, Rochester, MN(H.M.G., W.M.H.); Bir-mingham Veterans AffairsMedical Center and Divi-sion of Preventive Medi-

Affiliations continued atthe end of this article.

I n recent years, prescribers in the UnitedStates have made considerable efforts toreduce or discontinue opioids in patients

who have taken them long term. Cliniciansmay attempt dose reduction motivated by arange of patient-specific and environmentalconsiderations, including minimal benefitdespite stable, escalating, or high doses; stateregulations; medical board rules; payer andpharmacy policies; published guidanceaimed at reducing the quantity of prescribedopioids1; and concerns regarding adverse ef-fects, sanctions, overdoses, and opioid usedisorder (OUD).2,3 Evidence suggests thatindividual and societal benefits can emergefrom reduction efforts,4-8 but adverse conse-quences have also occurred, necessitatinggreater clarity around safe opioid taperingstrategies. Some patients benefit from opioid

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reduction when carried out skillfully in away that minimizes pain and withdrawalsymptoms7,8; however, reduction or discon-tinuation of substantial doses can be bothpainful and hazardous, particularly whenabrupt, as attested to by growing reportsfrom medical experts, federal agencies, andother stakeholders.1,9-15 Resultant harmsmay include serious withdrawal symptoms,psychological distress, self-medicating withillicit substances, uncontrolled pain, wors-ening function, and suicidality.9,11,15-19

A complicating factor in long-term opioidtherapy (LTOT) is that multiple agencies in-fluence clinical decisions. Notably, in 2016,the Centers for Disease Control and Preven-tion (CDC) Guideline for Prescribing Opioidsfor Chronic PaindUnited States was issuedto guide primary care clinicians who were

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considering initiating or continuing opioidprescriptions.20 It recommended avoidingopioid doses above 90 morphine milligramequivalents without careful clinical reviewand justification. Many states subsequentlyimposed fixed limits on dose and duration,measures that misapply the guideline recom-mendations.21 The Centers for Medicare andMedicaid Services, as well as pharmaciesand pharmacy benefit managers, have alsoimposed limitations that vary in their provi-sions for exceptions.2 Consequently, somepatients have encountered barriers to obtain-ing prescribed opioids or have experiencedsudden dismissal from care without adequatereferral, leaving them at risk for severe with-drawal and other iatrogenic harms.2 TheCDC guideline authors, warning againstguideline misapplications, published a clarifi-cation that the guideline does not supportabrupt tapering, sudden discontinuation, sud-den dismissal of patients, or hard limits ondosages and treatment durations.15 Suchabrupt discontinuation of opioid prescribingor dismissal from care (barring extremeextenuating circumstances) raises ethicalconcerns regarding patient rights to partici-pate in care decisions and be protected fromabandonment and its associated risks.1,22

These circumstances particularly affectso-called legacy patients, patients alreadyreceiving LTOT who seek continuation ofopioid therapy with a new physician afterlosing access elsewhere.18 Frequently, healthcare systems fail to facilitate transition ofcare when primary opioid prescribers leavetheir practice; therefore, these patients,some of whom have been receiving LTOTfor years, often present as desperate for asource of continuing LTOT. Concurrently,clinicians feel pressure to reduce or discon-tinue LTOT from health care organizations,ethical guidelines, insurance and pharmacypolicies, and even the US Drug EnforcementAdministration (DEA). Uncertainty aboutbest methods for opioid reduction may com-pound reluctance to accept legacy patients,who need special consideration and treat-ment to preserve their safety and func-tioning. The objective of the current articleis to clarify the indications and strategies

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for opioid reduction or elimination, to delin-eate the responsibilities of clinicians withcurrent or new patients receiving LTOT,and to provide recommendations forcompassionate and evidence-based care. Rec-ommendations are informed by the recog-nized biopsychosocial model of pain carethat optimizes individualized patient careand an interdisciplinary approach.23

METHODSThe American Academy of Pain MedicineFoundation convened an interdisciplinarypanel of pain clinicians and a patient advo-cacy representative. The panel (Appendix,available online at http://www.mayoclinicproceedings.org) met in Chicago,Illinois, on April 6, 2019, to identify anddiscuss key questions addressing the timing,indications, ethics, and methods surround-ing reduction or discontinuation of opioidsprescribed for chronic pain. Panelists brokeinto 3 work groups to evaluate assessment,ethics, and taper methods and presentedfindings to the full group. Recommendationspresented here are based on a survey of theexisting literature and on the collective clin-ical expertise of panelists. Review of litera-ture, which is sparse and generally notapplicable to weaning of therapeutic opioidsin a primary care setting, was not systematic.Panelists agreed on major points of discus-sion and were in full agreement on moststatements and recommendations. Whenagreement was incomplete, discussion andfurther literature reviews were conductedvia electronic communication. Deliberationscontinued through several rounds of manu-script drafts to reach final consensus.

RISKS OF LONG-TERM OPIOID THERAPYIt is axiomatic that a medical treatmentshould be continued only so long as benefitsexceed risks and harms. However, it can beunclear whether increased pain and decreasedfunction in a patient receiving LTOT are dueto opioids, disease progression, or psychoso-cial and environmental factors. Eliminatingopioids may create new symptoms andexacerbate existing ones, leading to theperception that the drug had been effective

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TAPERING OPIOID ANALGESICS

when it was not. Conversely, symptoms (eg,pain) unmasked when an effective medica-tion is reduced can erroneously be attributedto dependency and withdrawal. Reevaluatingthe underlying causes of pain is critical indetermining if other interventions (eg, phys-ical therapy, behavioral health, interventional,and complementary and integrative ap-proaches) may help to reduce pain andimprove psychosocial function before or inconjunction with an opioid taper.23

Risk is always present with LTOT and islinked to dose,24,25 dose variability (suggest-ing risks for both opioid prescribing anddeprescribing),26 use of concomitant seda-tives,26-28 and other factors (Table 1).24-31

In a cohort of almost 43,000 LTOT patients,Glanz et al29 found 9 overdose predictors inpatients on LTOT: age, mental illness, psy-chotropic medication, substance use disor-der, tobacco use, opioid prescriptions inthe year prior to initiating LTOT, long-acting/extended-release formulation, dailyopioid dose, and hepatitis C. Analysis of asample from the Veterans Health Adminis-tration confirmed that pain-related polyphar-macy and individual patient characteristicssuch as medical, psychiatric, and substanceuse comorbidities exacerbate risk.30

INDICATIONS FOR TAPERING LONG-TERMOPIOIDSIndications to taper in the course of LTOT(Table 2) may be as self-evident as a patient’srequest to try a different treatment or reduceto a safer dose. In patients who have beenreceiving LTOT, diminishing analgesia maybe a reason to taper opioids and intensify non-opioid pain care; however, it may also be anindication for trials of alternate opioids (ie,opioid rotation),32,33 as failure of an initialopioid trial may not predict failure with otheropioids.34 Diminishing analgesia after initialbenefit may suggest a need to evaluate the pa-tient for disease progression or for a new orpreviously unrecognized physical or mentalhealth condition. It may also indicate opioidanalgesic tolerance and that alternative treat-ments should be considered.

The targets of LTOT are improvementsin pain and function, which includes

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physical, cognitive, vocational, social, andother valued activities. Documenting func-tional improvements, quantitatively andqualitatively, may justify doses and dura-tions that exceed the current ceilings recom-mended by payers and others, even if suchassessments are imprecise. Conversely, inad-equate functional improvement suggests aneed for further assessment as tapering opi-oids may be indicated.

Opioids should be reduced or stoppedwhen they are harming the patient, as indi-cated by impaired function, unremittingaberrant behaviors, overdose,35 or otherserious adverse events.36 It should be notedthat both clinicians37 and patients38 mayhave difficulty accurately assessing theharms and benefits resulting from opioidsduring the conduct of LTOT, highlightingthe importance of quantitatively monitoringtherapeutic outcomes. In some patients, atrial taper can be the only method to deter-mine the harm to benefit ratio. An importantcriterion for reduction is the presence ofaberrant behaviors, typified by evidenceof multiple prescribers in prescriptiondrug-monitoring data, urine drug screen dis-crepancies, a pattern of stolen or lost pre-scriptions, frequent early refill requests,and repeated unsanctioned dose escalations.If such behaviors are multiple or severe andthe patient refuses referral to an addictionspecialist, clinicians may elect to discontinueor reduce opioids, concluding that their risksor harms exceed their benefits. Diverse is-sues such as personality changes, respiratorycompromise, and sleep apnea31 also mayrequire reconsideration of LTOT. A substan-tial number of patients receiving LTOT mayrequire tapering due to comorbid OUD,which can occur in vulnerable persons afterrepeated exposure to opioids and rendersthem unable to fully control their behavior,so that they continue to use opioids despitetheir causing harm.39

The question arises whether opioidsshould be tapered simply because the doseexceeds the cautionary thresholds offeredby the CDC20 or other agencies. Dosethresholds in guidelines are derived fromrisk calculations and do not incorporate

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TABLE 1. Patient Factors That Increase Risk With Long-Term Opioid Therapy

Factor Risk Reference

Daily dose >90-100 MME Overdose VA/DoD 201724

Volkow & McLellan 201625

Dose variability Overdose Glanz et al 201926

Long-acting or extended-release formulation(both long-term use and within 2 wk ofinitiation)

Overdose Volkow & McLellan 201625

Combination with benzodiazepines, otherrespiratory-depressant drugs

Overdose VA/DoD 201724


Sullivan 201827

Gressler et al 201828

Long-term use (>3 mo) Overdose,OUD

VA/DoD 201724


Age >65 y or <30 y Overdose,OUD

VA/DoD 201724


Adolescence OUD Volkow & McLellan 201625

Renal or hepatic impairment Overdose Volkow & McLellan 201625

Mental disorders, mental health diagnosis,psychiatric instability

Overdose,suicidality

VA/DoD 201724

Current or prior depression Volkow & McLellan 201625

Generalized anxiety disorder Glanz et al 201829

Borderline personality disorder Oliva et al 201730

Antisocial personality disorderPosttraumatic stress disorder

Respiratory compromise, including sleep apnea Overdose VA/DoD 201724


Walker et al 200731

Current or history of SUD OUD VA/DoD 201724

History of drug overdose Overdose VA/DoD 201724


Psychotropic medication use Overdose Glanz et al 201829

Oliva et al 201730

Smoking Overdose,OUD

Glanz et al 201829

Pain nonresponsive or worsened with opioids Overdose,OUD

VA/DoD 201724

Recent health care utilization for mental healthor SUD

Overdose,suicide,suicidalbehaviors

Oliva et al 201730

MME ¼ morphine milligram equivalent; OUD ¼ opioid use disorder; SUD ¼ substance use disorder; VA/DoD ¼ Veterans Affairs/Department of Defense.


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benefits, which are difficult to measure inpharmacoepidemiological studies. There isno inflection point above which opioidsabruptly become more dangerous, providedthe dose escalation is slow.40 However,dose thresholds are reasonable as flags toindicate the need for evaluation and


documentation to justify the dose. Indeed,prescribed dose correlates with overdoserisk.20,40-42 Coadministration of benzodiaze-pines and other sedating psychoactive medi-cations with opioids increases the risk ofoverdose,30,40 and those taking the highestdoses of opioids may be most likely to use




TABLE 2. Indications for Tapering Long-TermOpioids

Patient request

Diminishing analgesia

Diminishing function

Deteriorating quality of life not explained by medicalconditions

Unacceptable medical risk

Significant risk to benefit disparity

Active harms, including opioid use disorder

High risk: dose, medication combination(s)

Aberrant behaviors


this combination.43,44 While urgingclinicians to be judicious in prescribing toreduce opioid-related harms, the AmericanMedical Association Opioid Task Forceaffirmed that opioid therapy may be medi-cally appropriate for some patients, evenat doses exceeding federal agencies’recommendations.45

TABLE 3. Common Opioid Withdrawal Symptoms

Physical symptomsTremorDiaphoresisAgitationInsomniaMyoclonusDiffuse pain/hyperalgesiaHyperthermiaHypertensionCramping/diarrheaPupillary dilationPiloerectionRelease of stress hormonesPain increase

Affective symptoms

DysphoriaAnhedoniaAnxietyDepressionHopelessness/suicidal ideation

Such symptoms as seizures, delirium, and death, which areknown risks of sedative withdrawal, occur only rarely in opioidwithdrawal, except in seriously ill patients.

Recommendation 1: Recognizing OpioidTapering IndicationsMany patients taking higher than recom-mended opioid doses will be at high risk,given the established correlation of dosewith other opioid-related risks, and thusmay meet criteria for tapering. Most panel-ists agreed that high opioid doses shouldbe reduced unless the opioid has shownbenefit and alternative treatments are notbeneficial or feasible. Furthermore, opioidsin combination with benzodiazepines shouldbe reduced (or the benzodiazepine reducedor discontinued) unless the combinationhas shown benefit and alternative treatmentsare not beneficial or feasible. However,exceeding recommended opioid dose limita-tions is not in itself a sufficient reason to ta-per. There is insufficient evidence to adviseopioid reduction in patients who showbenefit from treatment and lack evidentadverse effects, aberrant behavior, or majorrisks. The determination that a treatmentshould not have been initiated is not equiva-lent to a decision that it should be stopped.As with all medications, the lowest effectivedose is appropriate, and regular


reassessment of risk and benefit is funda-mental. If high-dose opioids are to becontinued, the patient’s awareness that thedose exceeds recommendations and is asso-ciated with higher than usual risk shouldbe established and documented.

Clinicians should be aware that bupre-norphine (usually combined with naloxone)given as medication-assisted treatment(MAT) of OUD should not be reduced ordiscontinued in an attempt to comply withanalgesia guidelines. Similarly, there maybe less argument for taper of buprenorphine(with or without naloxone) when used as aplausible lower-risk alternative to traditionalopioids. This partial mu agonist has uniqueproperties that create a plateau inrespiratory-depressant effects. Furthermore,most patients with OUD who are taperedfrom buprenorphine relapse to the use ofmore dangerous opioids.46

Although it is essential to consider anddocument input from the patient and family,the final responsibility for the tapering deci-sion rests with the prescriber, who shouldnot continue a medically contraindicated

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TABLE 4. Ensuring Patient Safety During Opioid Taper

Decision Point Method Follow-up

Opioid risk outweighs benefit d Systematic assessment At each clinic visitDose d Input from patient/familyCombinations d Gain patient consent and

collaborationAberrant behaviorsd Clinician decision

determinative

Active harmsInsufficient analgesiaPsychiatric/medical comorbidities

Before initiating taper d Opioid taper agreement

d Address depression, anxiety,insomnia

d Consider OUD DSM-Vchecklist

d Offer support

d Offer other pain treatmentmodalities

d Discuss rate of taper,possible withdrawal

d Slow taper

If noncollaborative

d Explain decision

d Rapid reduction only ifimminent danger

d Continue to offer decreasingdoses

Initiate taper d Close observation, support Week 1

d Ensure availability (teamapproach if possible)

Daily, or as needed(virtual visits, phone)

d Manage withdrawalsymptoms (adjuvants)

� Week 2Every 2 wk, as needed

d Rate, based on tolerability:10% of previous week’sdose (faster) and 10% ofprevious month’s dose(slower) have beenrecommended; slowerpreferred with long-termuse

Weekly, if symptoms aresevere (team based)

Slow or pause taper asneeded

Poor response to taper d OUDBuprenorphine/naloxone

Initiation: Every 3-4 d tooptimize dosing

d Poor response to taperwithout OUD

BuprenorphineOR slow taper

Continued on next page


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TABLE 4. Continued

Decision Point Method Follow-up

d Advise patient of possiblewithdrawal

d Set target/follow-upbuprenorphine dose(s)

d Start behavioral program

DSM-V ¼ Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition); OUD ¼ opioid use disorder.


treatment solely on the basis of patientrequest. Tapering is essential if patients arein serious danger because of medical compli-cations, overdose,35 or hazardous (eg, inject-ing) behaviors. Clinicians should offer careto all patients who are dependent or whohave OUD, or else should obtain agreementfrom others to provide this care. Simply giv-ing the patient the name of another healthcare professional is inadequate andineffective.

Risks Associated With Opioid TaperingNumerous studies have documented thatmost patients who agree to taper eitherbenefit or are unharmed.7,8,47-49 Moststudies, however, lacked randomization andblinding and did not investigate the conse-quences of nonconsensual tapering. Vieweddifferently, credible evidence suggests thatvoluntary, patient-centered opioid reductionmostly yields good results with minimal tono documented harms; however, these re-sults cannot be generalized to other opioidtapering strategies. Furthermore, prelimi-nary data from patients undergoing consen-sual opioid taper indicate that a subgroupworsened with dose reduction.8 This findingmay indicate that the LTOT benefit was sig-nificant and justifies continuing opioid treat-ment in a minority of LTOT patients. Or, itmay indicate psychiatric comorbidity thatneeds evaluation and treatment. Moreresearch is needed in larger, diverse popula-tions to draw generalizable conclusions.

Reports of harms after involuntary opioiddiscontinuation include overdoses, termina-tion of care, emergent hospital or emergency


department utilization, and suicidal ideationor behavior.9,17-19,50 However, these reportsare difficult to interpret regarding causalitybecause reasons for opioid stoppage areeither not reported17,50 or include worri-some patient behaviors.17,19,51 Thus, it couldbe that patient-related factors (eg, substanceuse disorder) that precipitated opioiddiscontinuation played an independentcausal role in the harms that followed.That said, the poor outcomes make it hardto argue that stopping opioids resulted inbenefit. In practice, patients who are unwill-ing to reduce opioids are likely to drop outof treatment.50,52

The problems of tapering dropouts andearly opioid resumption are often triggeredby difficulty tolerating withdrawal whensymptoms are inadequately addressed, andfear of withdrawal is one reason patientscontinue LTOT.53 Dropouts also occur dueto patients’ fear that pain will worsen andpossibly become intolerable with opioidcessation. This fear must be taken seriouslyand addressed. It often goes unrecognizedthat pain itself may be a withdrawal symp-tom and not simply an exacerbation of theoriginal chronic pain.53 The increased painassociated with withdrawal may be new oramplified preexisting pain, as descendingpain facilitatory tracts originating in therostral ventral medulla show increased firingand amplify pain during early abstinence.54

Anxiety and depressive symptoms mayemerge or intensify during withdrawal. A2018 study of voluntary opioid taperingfound that greater depressive symptoms pre-dicted taper discontinuation.8

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TABLE 5. Buprenorphine Initiation in Patients Taking Opioids for Pain

d Buprenorphine may produce acute opioid withdrawal in patients on full mu agonists

d Patients discontinue all opioids the night before initiation (time depending on duration of action)

d After mild withdrawal is present, initiate 2-4 mg (repeated at 2-hour intervals, if well tolerated, until resolution ofwithdrawal symptoms)

d Typically, 4-8 mg will be needed the first day

d Reevaluate on day 2 and increase dose if needed

d Total dose given on day 2 can then be prescribed as the daily dose

d Unlike treatment for opioid use disorder, buprenorphine for analgesia should be given in 3-4 daily doses


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These realizations, along with a US Foodand Drug Administration (FDA) safetyalert12 warning of serious withdrawal symp-toms in patients abruptly discontinued fromopioids, underscore the importance of help-ing all patients avoid such symptoms(Table 3). Thus, withdrawal distress shouldbe preempted and treated with liberal useof adjuvant agents along with adequate clini-cian time and support. Clinicians shouldalso convey that many patients receivingLTOT actually feel and function betterfollowing opioid tapering.48,55-57

Less recognized than acute withdrawal isa syndrome that has been called protractedwithdrawal.58-60 Months after opioid elimina-tion, patients may experience dysphoria, irri-tability, insomnia, anhedonia, or a vaguesense of being unwell.59,61 These symptomsmust be expected, discussed with the patient,and either preempted or treated. Importantly,these symptoms cannot be easily differenti-ated from what is seen in patients withchronic pain who have not been treatedwith opioids and may reflect an unmaskingof the original chronic pain problem.

Recommendation 2: Reducing Risk DuringTaperReducing opioids comes with risks thatshould be appreciated and reviewed carefullywith the patient and their family (Table 4).Patients who agree to taper tolerate it better.Some patients become upset when changesare suggested. If the patient is depressedand is opposed to taper, treatment fordepression should be instituted before taperor taper should only be undertaken whenthe patient’s potential for self-harm is


recognized and addressed. The panel agreedthat taper should include a declared commit-ment to work with the patient on a safe,comfortable process with assurance thatthere will be no abandonment. Optimally,there should be a team-based approach thataddresses psychosocial as well as medical is-sues. It is recognized, however, that access tosuch a team is unavailable in many locations.The process may require considerable educa-tion, time, and counseling. Considerationmay also be given to referral to a painspecialist at this time to help ensure thatnonopioid treatments are optimized andthat the patient does not feel abandoned.Most symptoms of opioid withdrawal canbe mitigated or eliminated with the use ofadjuvants. Because poor results from outpa-tient tapers may result from insufficientphysician expertise as well as the inaccessi-bility of services, clinicians must developexpertise or refer to another health care pro-fessional with specialized skills.

METHODS OF OPIOID REDUCTIONThere is no established best way to reduce oreliminate opioids, and evidence to support aparticular taper rate is weak. Working withvoluntary patients, Darnall et al8 providedinitial reductions of 5% and continued slowreductions, usually in 10% decrements,over 4 months. Not all patients chose thisapproach, and for a minority, doses did notdecline but increased. The Washington StateAgency Medical Directors’ Group guidelinerecommended for most patients an initialreduction of 10% or less per week withfurther adjustments based on patient sta-tus.62 The CDC recommended 10% per





week reduction as a starting point.36 Morerecently, a guide from the US Departmentof Health and Human Services63 suggestedindividualized tapering plans that rangefrom 10% per month (or slower) to faster ta-pers of 10% per week until 30% of the orig-inal dose is reached, followed by 10% weeklyreductions of the remaining dose. Slow ta-pers may require several months or yearsand are more appropriate than faster tapersfor patients who have been receiving pro-longed LTOT.63 Because of complex and var-iable pharmacokinetics, nonlinear morphineequivalency, multiple drug interactions, anddocumented high lethality, outpatientsshould not be converted to methadone forweaning in the absence of special justifica-tion and clinician experience. This recom-mendation is especially true in those takinghigh doses of opioids.

Several authors described beneficial out-comes with treatment in chronic pain reha-bilitation programs based on aninterdisciplinary model that incorporatedopioid tapering in a context of psychosocialtreatments (cognitive behavioral therapy,mindfulness stress reduction, relaxationtraining, and pain education) and rehabilita-tion (physical and occupational therapy andgraded exercise).47,55,64-68 Taper (often tozero) commonly was completed in 3 to 4weeks, and dropouts were typically lessthan those reported in much slower outpa-tient approaches. Notably, program partici-pation was voluntary, taper was consensualin the setting of specialized programs, andpatients were often seen daily throughoutthe process.

Collectively, these reports and studiessuggest that the tolerability and success ofopioid tapering may depend less on theopioid dose than on the intensity of supportand observation and the ability of staff toprovide immediate intervention when thereis patient distress. This issue poses a majorchallenge for primary care clinicians andfor health systems. Importantly, the goal israrely the rapidity of reduction but ratherits durability over time, which is likely tobe contingent on maintaining patient com-fort and valued activities.


Pharmacological Adjuvants to OpioidReductionA number of medications mitigate physicaland psychological withdrawal symptoms.a2-Agonists directly attenuate opioid with-drawal.69 Clonidine suppresses withdrawalsymptoms but may cause orthostasis or hy-potension in some, necessitating small initialdoses and careful titration. Tizanidine is lesseffective but also less likely to cause hypo-tension. Lofexidine is FDA approved forcontrol of opioid withdrawal symptoms.63

An old and generally weak scientificliterature confirms the usefulness of agentsthat do not specifically counteract the phys-iologic changes of opioid withdrawal but domitigate anxiety, insomnia, and irritability.Drugs reported to have benefit for short-term use include trazodone,70 tricyclic anti-depressants,71 gabapentin,72 and mirtaza-pine.73 Gastrointestinal discomfort mayrespond to loperamide; however, cliniciansshould know that it can be abused and, inhigh doses, can cause dangerousarrhythmias.74

The Role of BuprenorphineBuprenorphine, a partial mu-receptoragonist, is approved in sublingual form fortreatment of OUD in combination withnaloxone. As noted at a 2018 National Acad-emies of Sciences, Engineering, and Medi-cine workshop on MAT of OUD,“Medications are irrefutably the most effec-tive way to treat OUDdreducing the likeli-hood of overdose death by up to three-fold.”

75

Buccal and cutaneous patches of low-dose buprenorphine are FDA-approved forthe treatment of pain, and buprenorphine/naloxone has been used off-label as an anal-gesic for chronic pain.76-78 Buprenorphinehas safety advantages over full mu agonistsbecause respiratory depression tends toplateau as dose increases, and it is also lesssubject to dose escalation. Although use ofbuprenorphine/naloxone to treat OUD re-quires training and a waiver from the DEA,no federal restrictions apply to its use as ananalgesic (although payers often denycoverage for off-label use). Studies have

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suggested efficacy in patients with comorbidchronic pain and OUD.79,80 Daitch et al,80 ina small retrospective review, found that pa-tients taking high doses of opioids for painexperienced substantial improvements inpain and quality of life when switchedfrom a full mu opioid receptor agonist tobuprenorphine.

Buprenorphine has been suggested forcertain patients who, despite substantialopioid doses, continue to manifest poor anal-gesia and function, yet worsen when opioidsare either reduced or increased. They oftenhave comorbid mood disorders or psychiat-ric diagnoses but do not meet criteria forOUD.58 Typically, such patients experienceprolonged symptoms from opioid reduction,even when supported, that may includehyperalgesia and anhedonia. Their sufferingsengender a desire to continue LTOT, yet, un-like patients with OUD, they do not craveopioids or use them compulsively.53,58 Thesituation has been described as complexpersistent dependence or complex persistentopioid dependence, terms intended to helpguide research and treatment of these chal-lenging patients but not proposed as diag-nostic nomenclature. (Importantly, oneshould avoid the error of assuming that alldeterioration resulting from opioid reduc-tion is due to dependence given that the pro-cesses that originally engendered the painare likely to remain active and could beunmasked by opioid reduction.)

Although large studies are lacking, suchpatients have responded well to buprenor-phine/naloxone.58,77,79 In support of thisfinding, the recent US Department of Healthand Human Services guide suggests a bupre-norphine trial in persons failing to benefitfrom high opioid doses yet respondingpoorly to taper.63 Therefore, the panelagreed that this difficult to handle situationmay warrant a trial of buprenorphine/naloxone, given that (1) neither opioid esca-lation nor reduction seem viable, (2) bupre-norphine/naloxone may reduce urges fordose escalation, and (3) the combination isdemonstrably safer than high doses of muagonists, which these patients are typicallytaking. (Because it has abuse-deterrent


properties, buprenorphine/naloxone ispreferred over buprenorphine alone.) Analternative treatment track is a very slowopioid dose taper, which may be selectedwhen patients cannot tolerate buprenor-phine, among other rationales.

Recommendation 3: Initiating TaperThe panel suggested the use of an opioid ta-per agreement or informed consent to be dis-cussed and signed by the patient andphysician and to contain such items as astatement of collaboration, a statement ofcommitment to treatment and teamwork,description of clinician responsibilities (eg,patient nonabandonment and commitmentto treat withdrawal and pain), and descrip-tions of patient responsibilities (eg, adher-ence to the collaborative treatment planand communication regarding difficulties)(Table 4). Before and during reduction,depression, anxiety, and insomnia shouldbe addressed. The panel recommended thataddiction assessment be conducted beforetapering because patients with OUD are un-likely to tolerate abstinence and are atheightened risk for using hazardous substi-tutes. This assessment may include adminis-tering the OUD checklist of the Diagnosticand Statistical Manual of Mental Disorders(Fifth Edition).39 If used, the clinicianshould be aware that many criteria for thediagnosis of OUD can also occur as a resultof chronic pain, thus risking false-positives.The panel endorsed making available bupre-norphine with or without naloxone in all de-livery systems and dosages for treatment ofpain without the necessity of an OUD diag-nosis. Panelists agreed that OUD can be diffi-cult to diagnose in those receiving LTOT andthat consultation or comanagement with anaddiction specialist is helpful if available.

d For patients with OUD, treatment withMAT is essential: clinicians shouldtreat with buprenorphine/naloxone ifauthorized by the DEA Drug AddictionTreatment Act of 2000 waiver for treatingOUD or should refer the patient for addic-tion treatment.





d For patients with poor pain control, poorfunctioning, and poor response to taperbut without OUD, 2 treatment paths maybe considered: (1) treatment with orreferral for treatment with buprenor-phine/naloxone or (2) slow opioid dose ta-per that may take months or years.

The manufacturer has provided guide-lines for safe buprenorphine initiation thatexceed the scope of this paper.81 Theseguidelines are for patients initiating MATfor addiction but are also applicable to pa-tients taking therapeutic opioids (Table 5contains panel recommendations).

Clinicians should initiate slow, reason-able, collaborative taper with adjuvant treat-ments as needed for withdrawal symptoms,counseling patients that such symptoms,should they occur, can be safely managed. Pa-tients should be encouraged to share owner-ship of the collaborative process and tounderstand that the health care professionalis not dismissing them, withdrawing fromtheir treatment, or giving up on managingtheir pain effectively. Clinicians should setpatients up for success by communicating atthe start regarding individualized goals, ex-pectations, patient fears, and the contingencyplans should problems arise (eg, slow orpause taper, clonidine, and other options).

Taper rate is determined by patients’ability to tolerate it. It may be helpful toimplement very small dose decreases at firstto address patient anxiety and to increasepatient confidence in the process. Percent-age reductions should not be understoodas a straight-line taper from the startingdose (which, in the case of 10% reductions,would subject a person starting at 1000morphine milligram equivalents to a reduc-tion from 100 mg to zero at the last decre-ment); rather, each new dose should be90% of the previous dose. The target dosemay not be zero, and some patients whoseregimens have been tapered to eliminationmay benefit from resumption at lowerdoses. Close observation and support dur-ing the taper are critical to the process asis clinician availability to treat symptomsand manage fears.


There may be a role for “virtual visits”via video in situations of limited access tothe caregiver. There is also a need for long-term follow-up, as periods of increasedpain can be expected at some point in timeand may require increased nonopioidstrategies.

Recommendation 4: Avoiding AbandonmentSuch practices as abrupt withdrawal or ma-jor dose reduction and “cold referrals” to cli-nicians who have not agreed to accept thepatient are unacceptable medical care exceptin extreme cases, such as confirmed diver-sion or serious medical toxicity, and eventhen, there may be risk of overdose in suchpoints of care transition.82 Sudden cessationis no more appropriate with opioids thanwith antihypertensives or antihyperglyce-mics. To reduce or discontinue LTOT, theclinician is obligated to (1) offer a comfort-able and safe tapering regimen, (2) obtainagreement from another physician to offercare, or (3) replace full mu agonists withbuprenorphine. These considerations applyeven more in the case of benzodiazepines,baclofen, carisoprodol, barbiturates, andother central nervous system depressantswhose abrupt cessation can cause significantmorbidity and even death (SupplementalTable, available online at http://www.mayoclinicproceedings.org).83-85

It is acceptable to continue higher thanrecommended doses of LTOT when thereare neither adverse effects nor aberrant be-haviors and the patient demonstrates func-tional and analgesic benefits.

Nonpharmacological Strategies for OpioidReductionLittle research specifically examines the roleof psychosocial treatments in reducing opi-oids in patients receiving LTOT.7,49 Further-more, a Cochrane review found only 11studies (1592 patients) in which pharmaco-logical treatment of addiction was comparedwith pharmacological plus psychosocial in-terventions.86 Only a small number of psy-chosocial interventions were studied, anddata were inadequate to compare them. Yetthe addition of psychosocial care was found

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to significantly reduce dropouts, rate ofopioid use during treatment and at follow-up, and clinical absences during treatment.Moore et al87 found that cognitive behavioraltherapy improved outcomes among prescrip-tion opioid users with OUD who were beingtreated with buprenorphine/naloxone buthad no effect on heroin users similarlytreated. A recent American Society of Addic-tion Medicine practice guideline proposes of-fering patients psychosocial treatment asdetermined by individual need but withoutallowing patient refusal or treatment un-availability to preclude or delay pharmaco-therapy.88 Exercise and fitness training areknown to reduce both chronic pain and anx-iety, suggesting that they may be useful intherapeutic opioid reductions; however,there are no available data on this topic. Inanimal models of opioid withdrawal, tread-mill exercise reduced physical signs ofopioid abstinence.89,90 It may be significantthat many of the studies showing patientimprovement with opioid elimination incor-porated intensive psychosocial treatmentsand physical rehabilitation.

Recommendation 5: Optimizing Non-pharmacological Opioid ReductionStrategiesPatients undergoing opioid reduction shouldbe referred for or encouraged to seek behav-ioral therapies as a strategy for reducingwithdrawal-related anxiety and increasingtreatment retention. It is likely but not docu-mented that such measures as meditation,yoga, and aerobic exercises may attenuatediscomfort related to opioid reduction.

SYSTEMIC CHANGES NEEDED

Delineation of the ProblemOne reason for the prescribing of dangerousdoses and combinations is the lack of alter-natives. Current incentives promote a briefvisit that ends with a prescription, and, un-surprisingly, this is what many patientswant and expect. It is not productive toeducate health care professionals on theimportance of optimizing nonopioid thera-pies while disincentivizing their provision.


Interdisciplinary pain rehabilitation pro-grams have repeatedly found that severelyimpaired patients with chronic pain canachieve good function and reasonable com-fort with a combination of psychosocialtreatments, physical reconditioning, andnonopioid analgesics.49 Yet, such treatmentsare available only to a small percentage ofthose who could benefit.

Recommendation 6: Aligning Health CareIncentives With Optimal Patient CareThe incentive structure of office practiceshould be aligned with optimal care. A majorstrategy for opioid reduction must be theprovision of access to integrated comprehen-sive pain care that utilizes multiple disci-plines within a biopsychosocial framework.The time required for education and coun-seling of patients with chronic pain suggeststhat reimbursement codes should providefor treatment analogous to diabetic educa-tion, the nursing care code for depression,or Centers for Medicare and Medicaid Ser-vices payment for cardiac rehabilitation.91

For reasons previously detailed, payers,pharmacies, pharmacy benefit managers,medical boards, and legislatures must recog-nize that rigid adherence to dose limitationsis not supported scientifically.

STATEMENT OF LIMITATIONSThe evidence for the recommendations setforth is suboptimal. Patients have rarelybeen randomized to opioid reduction ordiscontinuation. It is conceivable that thosewho improved were those whose conditionsno longer required opioids. It is possible thatthose who did poorly after opioid elimina-tion were discontinued from opioids becauseof aberrant behaviors or other factors thatled to poor outcomes. The larger discussionregarding long-term benefits of opioids forchronic, nonmalignant pain is controversialand beyond the scope of this article. Thepanel believed that the available data sup-ported the conclusions reached but acknowl-edged that subsequent investigations couldpoint to different conclusions.





CONCLUSIONSystem-wide initiatives to decrease opioid pre-scribing have hadmixed results. Althoughpop-ulation studies have suggested benefit, reportsof individual harms suggest increased suffering,procurement of illicit substances, and suicides.These results highlight the importance ofassessing the whole person when consideringopioid reduction or discontinuation. Dosereduction in a collaborative environment isindicatedwhen opioid risks or harms outweighdemonstrated benefits in pain and function.

Among the criteria for reduction inLTOT, daily dose is important but not deter-minative because neither a ceiling nor averageeffective dose has been established. Therefore,each patient’s dose should be individualized.Dose reduction is indicated when a patientis in significant danger with the provisionthat alternative care is available and offeredif tapering results in a worsening clinical sta-tus. Dose reduction may not be indicated inthe absence of serious risk when there is evi-dence of benefit. Although data are limited,voluntary opioid reduction appears to havethe best outcomes to date. Patient preferencesin opioid tapering should be documented. Awritten opioid reduction or discontinuationagreement may be useful to confirm the pa-tient’s responsibility to adhere to the planand the clinician’s commitment to providefacilitated access and support during taper.Nonconsensual dose reduction is justifiablewhen the current treatment involves signifi-cant danger to the patient, there are no bene-fits sufficient to justify this risk, and thepatient cannot be brought to understandthis. With confirmed diversion of controlledsubstances, immediate stoppage is justified.

Opioidmonotherapy is rarely optimal care.Nonopioid pharmaceuticals, interventionalpain management, psychosocial treatmentsfor pain control and improved coping, andrehabilitation strategies should be utilized forbest outcomes. Regular documentation oftreatment response, including quantitative as-sessments of pain and function and ongoingrisk-benefit analysis, is essential to facilitatedecisions by patients and clinicians as well asto justify those decisions to others.


It is contingent on payers, suppliers, andregulators to recognize and support flexi-bility in LTOT dosage and duration. It iscontingent on payers and regulators to pro-mote access to nonopioid treatments forchronic pain and to incentivize theirprovision.

Key takeaway points for practicinghealth care professionals include:

d Do not abruptly stop LTOT, except for rea-sons of diversion or extreme patient danger

d Do not abandon patients or make “cold”referrals to other clinicians

d Consider high dose a risk factor but notdeterminative for taper

d Seek patient consent and collaborationduring tapering

d Consider buprenorphine when tapering isindicated but poorly tolerated

d Monitor patients closely and provide sup-port, including referrals, during taper

d Diagnose and treat OUD when presentd Document treatment response

ACKNOWLEDGMENTSThe views presented in this work are thoseof the authors and do not necessarily repre-sent those of the US Department of VeteransAffairs or any funding agency.

Beth Dove, of Dove Medical Communi-cations, LLC, Salt Lake City, Utah, providedwriting assistance and editing for the sub-mitted manuscript in accordance with theguideline of the International Committee ofMedical Journal Editors defining the role ofauthors and contributors and received pay-ment for services from the foundation.

All authors contributed to the consensus-building discussions, analysis and interpreta-tion of data, drafting or critical revision ofthe manuscript for scientific soundness andintellectual content, and approval of the finalmanuscript.

SUPPLEMENTAL ONLINE MATERIALSupplemental material can be found online athttp://www.mayoclinicproceedings.org. Sup-plemental material attached to journal articles

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has not been edited, and the authors take re-sponsibility for the accuracy of all data.

Abbreviations and Acronyms: CDC = Centers for DiseaseControl and Prevention; DEA = Drug EnforcementAdministration; FDA = Food and Drug Administration; MAT= medication-assisted treatment; OUD = opioid use disor-der; LTOT = long-term opioid therapy

Affiliations (Continued from the first page of thisarticle.): cine, University of Alabama School of Medicine,Birmingham, AL (S.G.K.); Department of Psychiatry, YaleUniversity School of Medicine, New Haven, CT (A.M.);New England Mental Illness Research and Education Center,West Haven, CT (A.M.); Advanced Pain Clinic, HamptonVA Medical Center, Hampton, VA (A.M.); James A. HaleyVeterans Hospital and Department of Neurology, Universityof South Florida Morsani College of Medicine, Tampa(J.L.M.); Swedish Pain Services, Swedish Health System, Seat-tle, WA (S.P.S.); and Department of Psychiatry and Behav-ioral Sciences, Department of Anesthesiology and PainMedicine, and Department of Bioethics and Humanities,University of Washington School of Medicine, Seattle,WA (M.D.S.).

Grant Support: Support for the Opioid ReductionConsensus Panel Project of the American Academy ofPain Medicine Foundation was received as unrestrictedgrants from Collegium Pharmaceutical, Orexo US, Inc, andUS WorldMeds, LLC.

Potential Competing Interests: Dr Covington has been apaid consultant for Nektar and Heron Therapeutics, Inc.,Avenue Therapeutics, and Arbor Pharmaceuticals Dr Argoffhas served as a consultant for BioDelivery Sciences Interna-tional, Inc, Collegium Pharmacutical, Daiichi Sankyo Com-pany, Limited, Egalet Corporation, Grünenthal, Kaléo, Inc,US WorldMeds, LLC, Pfizer Inc, Eli Lilly and Company,Novartis AG, Scilex Pharmaceuticals, Inc, Teva Pharmaceu-tical Industries Ltd, Regeneron Pharmaceuticals Inc, and Ver-tex Pharmaceuticals Incorporated, has received honorariafor speaking from Allergan, Daiichi Sankyo Company,Limited, Amgen Inc, Teva Pharmaceutical Industries Ltd, EliLilly and Company, and Jazz Pharmaceuticals, Inc, and hasstock/stock options from Pfizer, Inc. Dr Hooten hasreceived grants from US WorldMeds, LLC. Dr Kertesz hasowned stock in Merck & Co, Inc, Abbott, and Johnson &Johnson Services, Inc (sold in 2017). Dr Murphy serves asa paid consultant for US WorldMeds, LLC. Dr Stanos hasbeen a paid consultant for Pfizer Inc, Salix Pharmaceuticals,and Scilex Pharmaceuticals, Inc. Dr Sullivan reports a grantfrom Pfizer Inc and personal fees from Revon Systems,Aetna Inc, and Chrono Therapeutics. The other authorsreport no competing interests.

Correspondence: Address to Edward Covington, MD,3050 Science Park Dr, Emeritus Office, Beachwood, OH44122 ([email protected]).

ORCIDEdward C. Covington: https://orcid.org/0000-0003-3834-3001; Halena M. Gazelka: https://orcid.org/0000-


0001-8368-1590; W. Michael Hooten: https://orci-d.org/0000-0001-5645-6355

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Ensuring Patient Protections When Tapering Opioids

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