the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

Opioid Treatment Guidelines Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain Roger Chou,1 Gilbert J. Fanciullo,2 Perry G. Fine,3 Jeremy A. Adler,4 Jane C. Ballantyne,5 Pamela Davies,6 Marilee I. Donovan,7 David A. Fishbain,8 Kathy M. Foley,9 Jeffrey Fudin,10 Aaron M. Gilson,11 Alexander Kelter,12 Alexander Mauskop,13 Patrick G. O’Connor,14 Steven D. Passik,15 Gavril W. Pasternak,16 Russell K. Portenoy,17 Ben A. Rich,18 Richard G. Roberts,19 Knox H. Todd,20 and Christine Miaskowski,21 FOR THE AMERICAN PAIN SOCIETY–AMERICAN ACADEMY OF PAIN MEDICINE OPIOIDS GUIDELINES PANEL 1Oregon Evidence-based Practice Center, Department of Medicine, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon. 2Pain Management Center, Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. 3Pain Research Center, Department of Anesthesiology, University of Utah, Salt Lake City, Utah. 4Pacific Pain Medicine Consultants, Encinitas, California. 5Division of Pain Medicine, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston. 6Seattle Cancer Care Alliance, Seattle, Washington. 7Pain Management Clinic, Kaiser Permanente Northwest, Portland, Oregon. 8School of Medicine, Neurological Surgery and Anesthesiology, University of Miami, Miami, Florida. 9Pain and Palliative Care Service, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York. 10Samuel S. Stratton Department of Veterans Affairs Medical Center, and Albany College of Pharmacy & Health Sciences, Albany, New York. 11Pain and Policy Studies Group, Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison. 12Epidemiology and Prevention for Injury Control (EPIC) Branch, California Department of Health Services, Sacramento, California (retired 2005). 13New York Headache Center, New York, New York. 14Section of General Internal Medicine, Yale University School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut. 15Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, New York. 16Laboratory of Molecular Neuropharmacology, Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, New York. 17Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, New York. 18School of Medicine, Division of Bioethics, University of California Davis. 19School of Medicine and Public Health, University of Wisconsin, Madison. 20Pain and Emergency Medicine Institute, Beth Israel Medical Center, New York, New York. 21Department of Physiological Nursing, University of California, San Francisco. Abstract: Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multi- disciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for The Journal of Pain, Vol 10, No 2 (February), 2009: pp 113-130 Available online at www.sciencedirect.com This article is based on research conducted at the Oregon Evidence-based Practice Center with funding from the American Pain Society (APS). The authors are solely responsible for the content of this article and the deci- sion to submit for publication. Address reprint requests to Dr Roger Chou, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239. E-mail: chour@ohsu.edu 1526-5900/$36.00 ª 2009 by the American Pain Society doi:10.1016/j.jpain.2008.10.008 113 m t - n r i i o a o collectively labeled ‘‘chronic noncancer pain’’ (CNCP). CNCP conditions, including common conditions such as back pain, osteoarthritis, fibromyalgia, and headache, are extremely prevalent and account for very large costs. For back pain alone, total health care expenditures in 2004 and 2005 were estimated at $85 to $100 billion.75 CNCP is a leading cause of disability16,128 and can have deleterious effects on ability to work, functional status and other quality of life domains. There are numerous treatments for CNCP and a com- prehensive assessment is needed in every case to guide therapeutic decision making. Some patients with CNCP are appropriate for focused therapy with a small number of modalities. Patients with more complex cases, includ- ing those with disabling CNCP, tend to experience better outcomes if they are managed using a comprehensive approach that integrates strategies to improve pain with those that address the functional impairment and psychosocial factors that are often associated with CNCP.88Whether the plan of care is limited or is designed to be more comprehensive, opioid therapy may be a use- ful component of the management plan.30,132 However, the selection of patients for an opioid trial, and decisions The American Pain Society (APS), in partnership with the American Academy of Pain Medicine (AAPM), com- missioned a multidisciplinary panel to develop evi- dence-based guidelines on COT for adults with CNCP. These recommendations are based on a systematic evi- dence reviewalso commissioned by theAPS andAAPM.19 Methods Panel Composition The APS and AAPM convened a multidisciplinary panel of 21 experts to review the evidence and formulate recom- mendations (see Appendix 1 for list of panel members). Two co-chairs (P.F. and G.F.) were selected by the APS and AAPM to lead the panel, which also included the Chair of the APS Clinical Practice Guidelines Committee (C.M.) and theAPSDirector of Clinical Guidelines Development (R.C.). Target Audience and Scope The intent of the guideline is to provide evidence- based recommendations for use of COT for CNCP in ronic noncancer pain. However, opioids are also ing opioid-related adverse effects and outcomes mendations presented in this document provide ion; informed consent and opioid management erapy; use of methadone; monitoring of patients dose opioid therapy, opioid rotation, and indica- d management of opioid-related adverse effects; e and when to obtain consultation; management egnancy; and opioid-related polices. erapy for chronic noncancer pain requires clinical d prescribing and on the assessment and manage- on, and diversion. Although evidence is limited in ncancer pain, this guideline provides recommen- nel after a systematic review of the evidence. id analgesics, risk assessment, monitoring, chronic about chronic opioid therapy (COT), must weigh poten- tial benefits of opioids against the risk of significant harms, including a wide range of adverse effects as well as adverse outcomes associated with abuse (refer to Appendix B, Glossary for definition) potential. Opioid prescriptions have increased substantially over the last 20 years,14,90 in part due to a growing consensus that opioid therapy is appropriate for some patients with CNCP.132 An increase in prescription opioid misuse (see Glossary) and mortality associated with opioid use has also been observed, affecting adolescent and adults of all ages.9Cliniciansandregulatorsmustjointlyseekabalanced approach to opioid use, acknowledging the legitimate medical need foropioids in somepatientswithCNCP,while concurrently recognizing the serious public health prob- lem of abuse (see Appendix B, Glossary), addiction (see Appendix B, Glossary) and diversion (see Appendix B, Glos- sary), and implement procedures to reduce these risks. r the Use of Chronic Opioid Therapy in Chronic Noncancer Pain carefully selected and monitored patients with ch associated with potentially serious harms, includ related to the abuse potential of opioids. The reco guidance on patient selection and risk stratifica plans; initiation and titration of chronic opioid th on chronic opioid therapy; dose escalations, high tions for discontinuation of therapy; prevention a driving and work safety; identifying a medical hom of breakthrough pain; chronic opioid therapy in p Perspective: Safe and effective chronic opioid th skills and knowledge in both the principles of opio ment of risks associated with opioid abuse, addict many areas related to use of opioids for chronic n dations developed by a multidisciplinary expert p ª 2009 by the American Pain Society Key words: Clinical practice guideline, opioids, opi pain. Editor’s Note: The American Pain Society and the Ameri- can Academy of Pain Medicine present this first of 3 articles in this 3-part report as a guideline for opioid treatment of noncancer pain. O pioid analgesics arewidely accepted for the treat- ment of severe acute pain and chronic pain re- lated to active cancer or at the end of life. In contrast, the use of chronic opioid therapy (COT, see Ap- pendix B, Glossary) to treat other types of chronic pain remains controversial. Chronic pain is defined by the In- ternational Association for the Study of Pain as ‘‘pain that persists beyond normal tissue healing time, which is assumed to be three months.’’59 Chronic pain may occur in the context of numerous diseases and syndromes.51,134 For the purposes of this guideline, all chronic pain dis- orders outside of cancer pain or pain at end of life are 114 Clinical Guidelines fo both primary care and specialty settings. The target audi- ence is all clinicians who provide care for adults with CNCP, including cancer survivors with chronic pain due to their cancer or its treatment. Management of cancer pain, pain at end of life, acute pain, postsurgical pain, labor pain, or CNCP in children and adolescents is outside the scope of this guideline. Separate APS guidelines ad- dress management of sickle cell pain5 and cancer pain.83 Funding and Conflicts of Interest Funding for the guideline was provided by the APS. The guideline was approved by the APS and AAPM, but the content of the guideline is the sole responsibility of the authors and panel members. All panelists were re- quired to disclose conflicts of interest within the preced- ing 5 years at all face-to-face meetings and before submission of the guideline for publication, and recused themselves from votes if a conflict was present. Conflicts of interest of the authors and panelmembers are listed in Appendix 1. Evidence Review This guideline is informed by an evidence review con- ducted at the Oregon Evidence-based Practice Center and commissioned by APS and AAPM.19 The panel devel- oped the key questions, scope, and inclusion criteria used to guide the evidence review. Literature searches were conducted through November 2007. Investigators reviewed 8,034 abstracts from searches for systematic reviews and primary studies from multiple electronic databases, reference lists of relevant articles, and sugges- tions from expert reviewers. A total of 14 systematic reviews and 57 primary studies (not included in previ- ously published systematic reviews) were included in the evidence report.19 Grading of the Evidence and Recommendations The panel used methods adapted from the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group to rate the recom- mendations included in this guideline.52 Each recom- mendation received a separate grade for the strength of the recommendation (strong or weak) and for the quality of evidence (high, moderate, or poor) (Appendix 2). In general, a strong recommendation is based on the panel’s assessment that potential benefits of following the recommendation clearly outweigh potential harms and burdens. Given the available evidence, most clini- cians and patients would choose to follow a strong rec- ommendation. A weak rating is based on more closely balanced benefits to harms or burdens, or weaker evi- dence. Decisions to follow a weak recommendation could vary depending on specific clinical circumstances or patient preferences and values. For grading the qual- ity of a body of evidence that supports a recommenda- tion, we considered the type, number, size, and quality of studies; strength of associations or effects; and consis- tency of results among studies.52 Chou et al Guideline Development Process The guideline panel met in person on three occasions between September 2006 and January 2008. At the first meeting, the panel developed the scope and key ques- tions used to guide the systematic evidence review. At the second meeting, the panel reviewed the results of the evidence review and drafted initial potential recom- mendation statements. In between the second and third meetings, panelists participated in a multi-stage Delphi process, in which the draft recommendations were ranked and revised. At each stage of the Delphi process, the lowest-ranked recommendations were eliminated. At the third meeting, the final set of recommendations and recommendation grades were finalized and ap- proved. Although a two-thirds majority was required for a recommendation to be approved, unanimous agreement was achieved on all but two recommenda- tions (5.2 and 5.3 each had 2 panelists voting against). After the third meeting, the guideline was written by various panel members and drafts distributed to the panel for feedback and revisions. Over twenty external peer reviewers were solicited for additional comments. After another round of revisions and panel approval, the guideline was submitted to the APS and AAPM Executive Committees for approval. The APS intends to update its clinical practice guide- lines regularly. This guideline and the evidence report used to develop it will be reviewed and updated by 2012, or earlier if critical new evidence becomes available. Recommendations 1. Patient Selection and Risk Stratification Recommendations 1.1 Before initiating COT, clinicians should conduct a history, physical examination and appropriate testing, including an assessment of risk of sub- stance abuse, misuse, or addiction (strong recom- mendation, low-quality evidence). 1.2 Clinicians may consider a trial of COT as an option if CNCP is moderate or severe, pain is having an adverse impact on function or quality of life, and potential therapeutic benefits outweigh or are likely to outweigh potential harms (strong recom- mendation, low-quality evidence). 1.3 A benefit-to-harm evaluation including a history, physical examination, and appropriate diagnostic testing, should be performed and documented be- fore and on an ongoing basis during COT (strong recommendation, low-quality evidence). Proper patient selection is critical and requires a com- prehensive benefit-to-harm evaluation that weighs the potential positive effects of opioids on pain and function against potential risks. Thorough risk assessment and stratification is appropriate in every case. This approach is justified by estimates of aberrant drug-related behav- iors (see Appendix B, Glossary), drug abuse, or misuse 115 in patients with CNCP, which range from 0% to 50%, depending on the population evaluated and methods used to define and identify these outcomes.57 Risk strat- ification pertaining to outcomes associated with the abuse liability of opioids—misuse, abuse, addiction and diversion—is a vital but relatively undeveloped skill for many clinicians.96 However, all clinicians prescribing opi- oids should be knowledgeable about risk factors for opi- oid abuse and methods for assessing risk. Assessment of risks for opioid-associated adverse effects also should be performed, given their high prevalence.86 A thorough history and physical examination, includ- ing an assessment of psychosocial factors and family his- tory, is essential for adequate risk stratification. Implicit in the recommendation to conduct a comprehensive ben- efit-to-harm analysis is the recognition that an opioid trial may not be appropriate. Clinicians should obtain ap- propriatediagnostic tests toevaluate theunderlyingpain condition, and should consider whether the pain condi- tion may be treated more effectively with nonopioid therapy rather than with COT. For example, COT gener- allywouldnotbeappropriatebeforea trial of ananticon- vulsant for trigeminal neuralgia,7 a disease-modifying antirheumatic drug for rheumatoid arthritis,27 a cortico- steroid for polymyalgia rheumatica,118 or various abor- tive and prophylactic therapies for migraine headache. Reliable evidence on methods to accurately assess the potential benefits of COT is limited. However, random- ized trials that demonstrate the benefits of COT are most applicable to patients with moderate or more se- vere pain who have not responded to nonopioid thera- pies.42,63 Presence of poorly-defined pain conditions, a likely somatoform disorder, or unresolved compensa- tion or legal issues may predict poorer response to all therapies, including COT.103,114 Although neuropathic and non-neuropathic pain conditions appear in general to respond similarly to COT,42,63,86 evidence that demon- strates the efficacy of COT for conditions with strong psychosocial contributors such as some types of chronic low back pain,74 daily headache,119 and fibromyalgia48 is sparse. There is insufficient evidence to recommend use of an intravenous opioid trial to predict likelihood of benefit from COT.63 The factor that appears to be most strongly predictive of drug abuse, misuse, or other aberrant drug-related behaviors after initiation of COT is a personal or family history of alcohol or drug abuse.28,35,60,72,85,111 Younger age and presence of psychiatric conditions are also asso- ciated with aberrant drug-related behaviors in some studies.28,35,60,84,111 Preexisting constipation, nausea, pulmonary disease, and cognitive impairment probably predict risk for opioid-related adverse effects, though no studies have adequately evaluated the utility of these factors for use in risk stratification. Clinicians should consider a trial of COT for CNCPwhen potential benefits are likely to outweigh risks, and there is no alternative therapy that is likely to pose as favorable a balance of benefits to harms. For example, a patient who is 60 years old, has chronic disabling osteoarthritis pain despite nonopioid therapies, and whose history re- 116 Clinical Guidelines fo veals no significant psychiatric comorbidities,majormed- ical comorbidities, or personal or family history of drug abuse or addiction would be assessed as having high po- tential benefits from COT relative to potential risks. COT couldbeprescribed to this patient inmost clinical settings with routinemonitoring (see Section 5). In contrast, a pa- tient who is 30 years old with fibromyalgia and recent in- travenous drug abuse would have high potential risks relative to benefits. COT in this context requires intensive structure,monitoring, andmanagementbyprofessionals with expertise in both addictionmedicine and pain med- icine and should be undertaken only if risks can be ade- quately managed (see Section 6). The selection of patients between these two extremes requires careful as- sessment and characterization of patient risk and struc- turing of care to match risk (see Section 5). In patients with a history of substance abuse or a psychiatric comor- bidity, this may require assistance from persons with ex- pertise in managing pain, addiction or other mental health concerns (see Section 6), and in some cases opioids may not be appropriate or should be deferred until the comorbidity has been adequately addressed. Screening tools that assess the potential risks associ- ated with COT based on patient characteristics are likely to be helpful for risk stratification, though more valida- tion and prospective outcome studies are needed to understand how their use predicts and affects clinical outcomes. Tools that appear to have good co