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Tapering Long-term Opioid Therapy in Chronic Noncancer Pain: Evidence and Recommendations for Everyday Practice Chantal Berna, MD, PhD; Ronald J. Kulich, PhD; and James P. Rathmell, MD CME Activity Target Audience: The target audience for Mayo Clinic Proceedings is primar- ily internal medicine physicians and other clinicians who wish to advance their current knowledge of clinical medicine and who wish to stay abreast of advances in medical research. Statement of Need: General internists and primary care physicians must maintain an extensive knowledge base on a wide variety of topics covering all body systems as well as common and uncommon disorders. Mayo Clinic Proceedings aims to leverage the expertise of its authors to help physicians understand best practices in diagnosis and management of conditions encountered in the clinical setting. Accreditation: Mayo Clinic College of Medicine is accredited by the Accred- itation Council for Continuing Medical Education to provide continuing med- ical education for physicians. Credit Statement: Mayo Clinic College of Medicine designates this journal- based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s). ä Physicians should claim only the credit commensurate with the extent of their participation in the activity. Learning Objectives: On completion of this article, you should be able to (1) appropriately identify circumstances when tapering chronic opioid ther- apy (COT) in patients with chronic noncancer pain should be considered; (2) recognize withdrawal symptoms during a COT taper, classify them for severity, and choose an adequate treatment; (3) apply strategies for medico-legal risk management during a COT taper, including using an opioid taper agreement. Disclosures: As a provider accredited by ACCME, Mayo Clinic College of Medicine (Mayo School of Continuous Professional Development) must ensure balance, independence, objectivity, and scienti f c rigor in its educa- tional activities. Course Director(s), Planning Committee members, Faculty, and all others who are in a position to control the content of this educational activity are required to disclose all relevant f nancial relationships with any commercial interest related to the subject matter of the educational activity. Safeguards against commercial bias have been put in place. Faculty also will disclose any off-label and/or investigational use of pharmaceuticals or instru- ments discussed in their presentation. Disclosure of this information will be published in course materials so that those participants in the activity may formulate their own judgments regarding the presentation. In their editorial and administrative roles, William L. Lanier, Jr, MD, Terry L. Jopke, Kimberly D. Sankey, and Nicki M. Smith, MPA, have control of the content of this program but have no relevant f nancial relationship(s) with industry. Dr Berna received salary support in part through an unrestricted educational grant from Purdue Pharmaand inpart froman Advanced Postdoc Mobilitygrant of the Swiss National Science Foundation (P3SMP3_151710). Purdue Pharma had no input or in uence into the conception, design, or preparation of this manuscript. Method of Participation: In order to claim credit, participants must com- plete the following: 1. Read the activity. 2. Complete the online CME Test and Evaluation. Participants must achieve a score of 80% on the CME Test. One retake is allowed. Visit, select CME, and then select CME ar- ticles to locate this article online to access the online process. On successful completion of the online test and evaluation, you can instantly download and print your certi f cate of credit. Estimated Time: The estimated time to complete each article is approxi- mately 1 hour. Hardware/Software: PC or MAC with Internet access. Date of Release: 6/1/2015 Expiration Date: 5/31/2017 (Credit can no longer be offered after it has passed the expiration date.) Privacy Policy: Questions? Contact [email protected] Abstract Increasing concern about the risks and limited evidence supporting the therapeutic bene f t of long-term opioid therapy for chronic noncancer pain are leading prescribers to consider discontinuing the use of opioids. In additiontoovert addiction or diversion,the presence ofadverse effects, diminishinganalgesia,reducedfunction and quality of life, or the absence of progress toward functional goals can justify an attempt at weaning patients from long-term opioid therapy. However, discontinuing opioid therapy is often hindered by patients psy- chiatric comorbidities and poor coping skills, as well as the lack of formal guidelines for the prescribers. The aim of this article is to review the existing literature and formulate recommendations for practitioners aiming to discontinue long-term opioid therapy. Speci f cally, this review aims to answer the following questions: What is an optimal opioid tapering regimen? How can the risks involved in a taper be managed? What are the alter- natives to an opioid taper? A PubMed literature search was conducted using the keywords chronic pain com- bined with opioid withdrawal , taper , wean and detoxi f cation . Six hundred ninety- f ve documents were identi f ed and screened; 117 were deemed directly relevant and are included. On the base of this literature review, this article proposes evidence-based recommendations and expert-based suggestions for clinical practice. Furthermore, areas of lack of evidence are identi f ed, providing opportunities for further research. ª 2015 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2015;90(6):828-842 From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School (C.B., R.J.K., J.P.R.), and Tufts University School of Dental Medicine (R.J.K.), Boston, MA. SYMPOSIUM ON PAIN MEDICINE 828 Mayo Clin Proc. n June 2015;90(6):828-842 n n ª 2015 Mayo Foundation for Medical Education and Research
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R ecent systematic reviews and meta- analyses suggest that long-term opioid treatment for chronic noncancer pain (CNCP) is supported by limited evidence. 1-10 First, the published studies of long-term opioid treatment for CNCP present the following issues, as reviewed in a recent Cochrane meta-analysis: few randomized clinical trials, a high discontinuation rate (up to 30%) of opioid therapy in the observed populations because of adverse effects or insuf f cient pain relief, and a relatively short observational period (6-48 months; mean, 15.15 months). 5 Second, the re- sults of these trials provide only weak evidence that long-term opioid therapy can provide clini- cally signi f cant pain relief and fail to provide any conclusive evidence for improved quality of life or function. 5 Amongthe 4.3 millionAmericanpatients pre- scribed opioids, 11 often for CNCP, many present an unfavorable risk-bene f t ratio for this treat- ment. 12 Although noting situations when a taper might be necessary, current guidelines regarding long-term opioid treatment in CNCP, whether published by multidisciplinary expert groups suchas theAmericanPain Society andthe Amer- ican Academy of Pain Medicine, or regulating organizations such as the Federation of State Medical Board, focus on how to prescribe safely and effectively but do not provide practical adviceonopioidtreatmentdiscontinuation. 13,14 The burden of tapering long-term opioid treat- ment often falls on community pain practices and individual physician practices, where re- sources are relatively limited, rather than tertiary centers. Yet, practitioners face patients present- ing with psychiatric comorbidities, such as per- sonality disorders, somatic symptom disorder, substance use disorder (SUD), 15-17 and depres- sion, 18 as well as poor coping abilities. 19 The available literature was reviewed to formulate evidence-based recommendations on tapering long-term opioid treatment in CNCP, speci f cally aiming to answer the following questions: What is an optimal opioid tapering regimen? How can the risks involved in a taper be managed? What are the alternatives to an opioid taper? INDICATIONS FOR TAPERING OF LONG-TERM OPIOID TREATMENT Adverse effects often outweigh the bene f ts of long-term opioid treatment: sedation, decreased concentration and memory, drowsiness, changes in mood, constipation, dry mouth, abdominal pain, nausea, hormonal changes with conse- quences such as sexual dysfunction, and osteo- penia may limit treatment tolerability. 4,5 The bene f ts of long-term opioid treatment can also be questioned when a patient reports inad- equate analgesia despite high doses (tolerance), reduced function, quality of life, or absence of progress toward therapeutic goals. 13 Table 1 presents the indications for tapering long-term opioid treatment. 14,20 Tapering might also be considered for patients planning elective sur- gery. According to a retrospective trial, patients with CNCP undergoing long-term opioid treat- ment (N ¼ 30) experience more postoperative pain than controls without long-term opioid treatment (N ¼ 25). 21 However, there is no research yet on the effect of preoperative tapering on postsurgical pain outcomes. Diversion and addiction are alarming but relatively uncommon considering the number of patients undergoing long-term opioid treatment. 7,22-24 Addiction (ie, SUD or more speci f cally opioid use disorder [OUD]) is a psy- chiatric diagnosis that involves use despite nega- tive consequences and/or loss of control over use, compulsions, and cravings. 25 Among pa- tients with chronic pain, adherence vs abuse can be seen on a spectrum, 12 and OUD is a dif f - cult diagnosis to establish with certainty, justi- fying involvement of an addiction specialist for initial evaluation and follow-up. 26,27 Although the current review aims to focus on patients with CNCP, patients with cancer pain may develop similar dif f culties related to opioid use. 28 Diversion (ie, any act that results in another individual receiving the medication than the one it was prescribed to) is a legal issue discussed further below. CENTRAL ISSUES DURING TAPERING OF LONG-TERM OPIOID TREATMENT Short-term Risks Withdrawal Syndrome. Opioid withdrawal syndrome is characterized by signs and symp- toms of sympathetic stimulation (due to decreased sympathetic antagonism by opioids), which has been well described in patients with SUD: anxiety, hypertension, tachycardia, rest- lessness, mydriasis, diaphoresis, tremor, piloer- ection, nausea, abdominal cramps, diarrhea, TAPERING OPIOID THERAPY FOR NONCANCER PAIN Mayo Clin Proc. n June 2015;90(6):828-842 n 829
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SYMPOSIUM ON PAIN MEDICINE Tapering Long-term Opioid Therapy in Chronic Noncancer Pain: Evidence and Recommendations for Everyday Practice Chantal...
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