The Use of Opioid Analgesics for Chronic Pain: Minimizing the Risk for Harm

Transcription

1 nature publishing group CLINICAL AND SYSTEMATIC REVIEWS 3 see related editorial on page x The Use of Opioid Analgesics for Chronic Pain: Minimizing the Risk for Harm Charles E. Argoff, MD 1 and Eugene R. Viscusi, MD 2 Chronic noncancer pain is common and consequential, affecting ~ 100 million people in the United States alone and costing, when direct and indirect costs are combined, in excess of $ 635 billion. For certain individuals, opioids may be an effective option for the management of chronic pain; however, a series of critical decisions must be made before prescribing opioids to ensure that their potential benefits and possible risks are appropriately and realistically addressed. A thorough history, physical examination, and appropriate testing, including an assessment of risk for substance abuse, misuse, or addiction, should be conducted in patients who are being considered for opioid therapy. Proactively developing a treatment plan that matches the needs and expectations of the patient, while minimizing the potential for substance abuse, is central to the success of pain management. Current standard of care suggests that for most patients, a trial of nonopioid therapies should generally be tried first. There is no single opioid of choice that universally provides the best outcomes for all patients; thus, it is critical for the health-care practitioner to become familiar with the available subclasses, formulations, and modes of administration, and base the treatment plan on clinical experience with the drug, prior patient experience, the availability of the formulation, and cost and coverage. Pain is a dynamic phenomenon in that its characteristics and response to treatment evolve over time, as does the patient s general health state. Both positive and negative changes over time may necessitate a change in medication. Opioids can be prescribed safely and effectively, and when used with appropriate attention to individual patient characteristics may have a positive impact on pain and function. When contemplating initiation of opioid analgesics, clinicians would do well to make it clear to their patient that they will be prescribed on a trial basis with a clear exit strategy for discontinuing such treatment if there is no clear benefit including lack of analgesia, insurmountable adverse effects, and / or frank misuse or abuse of the prescribed drug. Am J Gastroenterol Suppl 2014; 2:3 8; doi: /ajgsup INTRODUCTION Acute pain, or pain that is of relatively short duration, may be biologically useful as a symptom of a disease or injury. In clear contrast, chronic pain that which persists beyond the time of normal healing or beyond 3 months is often maladaptive. Chronic noncancer pain is a true, perhaps too silent epidemic that affects ~ 100 million people in the United States alone and results in estimated combined direct and indirect costs of $ 635 billion ( 1 ). Examples of common chronic noncancer pain syndromes include osteoarthritis, low back pain, headache, and neuropathic pain. Th is supplement focuses on the management of the gastrointestinal (GI) adverse effects of opioids, and more specifically on the management of opioid-induced constipation. However, even before opioids are considered, a series of critical decisions must be made to ensure that the benefits and risks of these medications are appropriately balanced and a treatment plan developed; pragmatic decisions must also be made regarding secure prescribing and the potential for addiction. Here, we will focus primarily on these aspects of opioid prescribing. Opioid analgesics are generally prescribed once nonopioid therapeutic approaches have been shown to be ineffective or contraindicated. When contemplating initiation of opioid analgesics, clinicians would do well to make it clear that they will be prescribed on a trial basis, and the clinician must have a clear exit strategy for discontinuing treatment if there is no clear benefit (e.g., lack of analgesia, insurmountable adverse effects, and / or frank misuse or abuse of the prescribed drug). When used in appropriate patients with reasonable precautions and ongoing follow-up, opioid treatment can be a powerful, effective, and safe tool in the arsenal of the clinician to treat otherwise intractable pain. AS CLINICIANS, WHAT CAN WE DO TO ENSURE APPROPRIATE AND EFFECTIVE OPIOID USE? The decision-making process involved in determining whether a patient is a candidate for chronic opioid therapy and can safely 1 Department of Neurology, Albany Medical College, Albany, New York, USA ; 2 Department of Anesthesiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Correspondence: Charles E. Argoff, MD, Department of Neurology, Albany Medical College, 47 New Scotland Avenue, MC 70, Albany, New York 12208, USA. cargoff@nycap.rr.com 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY Supplements

2 4 Argoff and Viscusi Comprehensive pain management plan Continue opioid therapy Patient selection Initial patient assessment Trial of opioid therapy Patient reassessment Implement exit strategy Figure 1. A critical thinking model for chronic opioid therapy. Alternatives to opioid therapy use these agents is as important as the selection of appropriate therapy ( Figure 1 ) ( 2 ). Before initiating chronic opioid therapy, the health-care provider should conduct a thorough history, physical examination, and appropriate testing, including an assessment of risk of substance abuse, misuse, or addiction ( 2 ). Perhaps surprisingly, the prevalence of opioid abuse among patients treated in chronic pain practices is unknown; however, some studies suggest that it is no more frequent than the prevalence of opioid abuse in the general population; ( 3 ) others have suggested that patients with chronic pain are at markedly increased risk for opioid misuse ( 4,5 ). One study found that the prevalence of addictive disorders was as high as 60 % among patients who have sustained major trauma ( 6 ). Among patients who are appropriate for opioid therapy, an effort must be made to develop a comprehensive pain management plan, including identification of alternatives to opioids. Once an agent has been identified, the patient must be periodically reassessed to determine the value of continuing therapy or implementing an exit strategy. Dose escalation should only occur when there is a proportional benefit to dosing. Here, we will consider each of the steps in this process. Clinical assessment A comprehensive clinical assessment should include a thorough medical history and physical exam, as well as the results of prior work ups, diagnostic tests, and the efficacy and adverse effects of prior treatment regimens. The nature, intensity, location, and effect of pain on physical and psychological function should be documented. If opioids are to be considered, it is also important to determine whether the patient has a personal or family history of opioid abuse. It is important to identify the underlying disorders that are causing the pain (if possible) and comorbid conditions that may exacerbate pain. Diagnostic testing frequently needs to be completed to achieve this. Some patients such as those with neuropathic pain may have an underlying disorder that can be cured or improved with disease-specific therapy; eg, vitamin B 12 deficiency neuropathy or an entrapment neuropathy ( 7 ). All patients suspected of having chronic pain should be questioned about their pain history and receive a pain-specific sensory examination, a musculoskeletal and myofacial evaluation, and a basic psychological assessment. A patient s functional status can be assessed by evaluating their ability to perform routine activities of daily living as well as their mood, ability to sleep, and coping skills ( 8 ). Psychosocial factors, such as anxiety, depression, posttraumatic stress disorder, substance abuse, or work issues, may complicate treatment responses and require specific intervention ( 9 ). Thus, psychosocial assessment is vital to the initial and often the ongoing evaluation of the patient with chronic pain ( 10 ). The experience of pain is, necessarily, highly individual. Thus, asking the patient how much pain they are in, while valuable, yields a non-quantifiable result. Simple unidimensional pain scales therefore have a great deal of utility for the initial assessment of pain as well as for following the efficacy of therapy. Several are available and easy to use ( 11 ). A verbal pain intensity scale, ranging from no pain to the worst possible pain, is useful and simple to use at the bedside. A 0 10 numeric pain intensity scale can be selfadministered, administered at the patient s bedside, or even over the phone. The conventional visual analog scale, ranging from no pain to worst possible pain, is another alternative for the assessment of pain. Notably, one meta-analysis of 54 studies including pain scales (primarily for postsurgical pain) suggests that there is better compliance, better responsiveness and ease of use, and greater acceptance of numeric rating scales compared with either visual analog scales or verbal rating scales ( 11 ). The assessment of pain must be performed with consideration of the individual patient (e.g., age, health condition and cognitive function). For example, many older patients may have difficulty using visual analog scales due to physical limitations. The Wong Baker FACES pain rating scale may be useful for patients aged 3 years and older, as well as cognitively impaired adults. On this scale, Face 0 indicates no pain at all, Face 1 feels mild pain, Face 2 feels moderate pain, Face 3 feels severe pain, Face 4 feels very severe pain, and Face 5 feels the worst possible pain. It can be used as is or with the brief word descriptions under each number. Patients with cognitive impairments and limited ability to communicate, such as stroke patients, may have difficulty with any self-reported pain assessment scale. For these patients, it is necessary for the physician to rely on behavioral observation of facial expressions, movement patterns (bracing, guarding, distorted postures, and avoidance of activity), and nonverbal sounds (moans and winces) and reports of significant others, including partners and children, to judge pain intensity accurately. When should a trial of opioid therapy be considered? Proper patient selection for opioid therapy is important to ensure a balance can be struck among safety, efficacy, and tolerability ( 2 ). Patients are appropriate candidates for opioid analgesics only after the persistence of significant pain despite reasonable trials of nonopioid analgesics and / or adjuvant medications or if moderate to severe pain ( 4 5 on a 10-point scale) requires rapid relief. Patients may also be candidates for opioid therapy if individual patient characteristics contraindicate the use of other analgesics. The American Journal of GASTROENTEROLOGY Supplements VOLUME 2 ISSUE 1 SEPTEMBER

3 The Use of Opioid Analgesics for Chronic Pain 5 Table 1. Ten universal precautions for all patients being considered for opioid therapy 1. Diagnosis with appropriate differential 2. Psychological assessment including risk of addictive disorders 3. Informed consent (verbal or written / signed) 4. Treatment agreement (verbal or written / signed) 5. Pre- / post-intervention assessment of pain level and function 6. Appropriate trial of opioid therapy adjunctive medication 7. Reassessment of pain score and level of function 8. Regularly assess the Four A s of pain medicine: analgesia, activity, adverse reactions, and aberrant behavior 9. Periodically review pain and comorbidity diagnoses, including addictive disorders 10. Documentation Adapted from Gourlay ( 12 ). In every case patients must be assessed to ensure that the benefits of opioid therapy are likely to outweigh the risks of such treatment. An important caveat to consider is that opioid therapy should be viewed as one component of a multimodal treatment approach to chronic pain. Universal precautions in pain medicine A unified, 10-step approach to the assessment and management of patients with chronic pain has been proposed and published ( Table 1 ) that can assist in the responsible prescribing of opioid therapy (12,13 ). First, underlying conditions that are causing the pain should be identified (where they exist) and addressed if possible. In the absence of specific objective findings, the symptoms should be treated. It is also critical to address comorbid conditions (including substance abuse disorders and other psychiatric illnesses) to reduce the risks for adverse events, drug interactions, and longterm opioid dependence. Second, all patients should undergo psychological assessment, including an assessment of their risk for addictive disorders ( 12 ). Such assessments should be conducted in a manner that is not seen by the patient as diminishing their personal pain experience, and must include a complete inquiry into past personal and family history of substance misuse; while a past personal or family history of drug use does not preclude the use of opioids entirely, they are serious warning flags that the patient should be monitored more closely. Urine drug testing for illicit and unprescribed licit drugs can be an effective tool in therapeutic decision making and should be discussed with all patients; those refusing such assessments should be considered unsuitable for opioid therapy. Th ird, the patient should be fully informed about the anticipated benefits and risks associated with opioid therapy, including the risk of addiction, physical dependence, and tolerance, at a level that is appropriate to the patient s individual capacity for understanding ( 12 ). Verbal and / or written informed consent should be obtained. Fourth and as a part of informed consent the expectations and obligations of the patient and the health-care provider should be clearly understood and outlined. In many cases, a formal treatment agreement can be valuable to help clarify boundary limits, making it easier to identify and intervene in cases of aberrant behavior ( 12 ). Th e fifth component of responsible opioid prescribing centers on tracking the effects of the medication on pain ( 12 ). All treatment plans should begin with an assessment of preintervention pain in order to effectively track and compare pain relief during ongoing assessment. Sixth, a trial of the first-choice medication, with or without adjunctive therapy, should be conducted. The response to these medications is highly dependent on the individual patient s experience of pain; furthermore, the adverse effects of opioids are highly variable and patient dependent. Thus, medication(s) should be trialed and therapy adjusted on an individual basis. As with the treatment of hypertension, for example, no single class of blood pressure lowering drug is appropriate for all hypertensive individuals. No health-care provider would continue a blood pressure lowering regimen that was not lowering a person s blood pressure. In those instances, a different class of medication or approach would be taken. Similarly, all patients prescribed opioid therapy for chronic pain will not respond favorably. Patients need to be aware of this and should be advised by the prescriber that the use of opioid therapy is on a trial basis. Seventh, patients should be regularly reassessed to help document the rationale to continue to modify the current therapeutic trial. It may be helpful, in many cases, to obtain corroborative support from family or other knowledgeable third parties to help understand whether the current trial should be modified or continued. Steps 8 through 10 should be routine among all patients who receive opioid medications, yet often are dismissed in clinical practice ( 12 ). First, evaluations of the 4 A s of pain medicine that is to say, analgesia, activity, adverse effects, and aberrant behavior should be conducted to help document therapy and support any changes in medication regimen ( 12 ). At the same time, it must be recognized that the illness underlying pain as well as comorbid conditions will evolve over time. Thus, it is essential to periodically perform a comprehensive review of the pain patient and medication adjusted as required. Finally, throughout the pain management process, it is important to proactively document the initial evaluation and ongoing assessments. Complete documentation not only increases the likelihood of successful pain management but also reduces medical legal exposure and the risk for regulatory sanctions. Assessing risk for aberrant behaviors / harm Assessing the individual s risk for opioid misuse is a prerequisite for successful therapy. Patients should be stratified according to their risk for aberrant behaviors ( Table 2 ) ( 14 ), although it should be noted that aberrant behaviors can also be seen in patients who are not abusing opioids ( 14 ). In one study of patients with chronic noncancer pain, major and minor aberrant behaviors were seen in 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY Supplements

4 6 Argoff and Viscusi Table 2. Aberrant drug-taking behaviors ( 32,33 ) Major Recurrent prescription losses Selling prescription drugs Prescription forgery Stealing or borrowing another patient s drugs Injecting or snorting oral formulation Obtaining prescription drugs from nonmedical sources Concurrent abuse of related illicit drugs Multiple unsanctioned dose escalations Minor Aggressive complaining about need for higher doses Drug hoarding during periods of reduced symptoms Requesting specifi c drugs Acquisition of similar drugs from other medical sources Unsanctioned dose escalation 1 2 times Unapproved use of the drug to treat another symptom Reporting psychic effects not intended by the clinician nearly half of patients, with 25 % demonstrating 1 2 such behaviors, 8.5 % demonstrating 3 4, and over 10 % demonstrating 5 or more. In the absence of formal screening, low-, moderate-, and highrisk patients can be distinguished based on specific behaviors. Low-risk patients are characterized by no past or current history of substance abuse, little if any family history of substance abuse, and no major or untreated psychological disorder. Moderate-risk patients may have a history of treated substance abuse and / or a significant family history of substance abuse, and may have a past or current psychological disorder. High-risk patients are those who have an active addiction and / or a major untreated psychological disorder. Formal risk stratification tools are useful to estimate which indivi duals may develop aberrant behaviors when prescribed opioids for chronic pain. The Opioid Risk Tool, developed by Webster and Webster ( 14 ), is one such tool. This simple, patientreported measure includes five items that are dichotomized based on gender, including family and personal history of substance abuse (including, as separate items, alcohol, illegal drugs, and prescription drugs), age (with ages being considered higher risk), history of preadolescent sexual abuse, and psychological disease (including two groups: attention deficit disorder, obsessive-compulsive disorder, bipolar disease, and schizophrenia and depression). The individual scores are summed to arrive at a total score ranging from 0 to 3 (low risk) to 8 (high risk). This assessment was evaluated in 185 new patients treated in a pain clinic; among those in the low-risk category, 17 out of 18 (94.4 % ) did not display aberrant behavior, and among those in the high-risk category, 40 out of 44 (90.9 % ) displayed an aberrant behavior. Alternatives to opioids for patients at high risk for aberrant behaviors should be considered if at all possible. A GOOD START: DEVELOPING AN OPIOID TREATMENT PLAN Developing a treatment plan that matches the needs and expectations of the patient while minimizing the potential for substance abuse is central to the success of pain management. A broad range of agents is available; of these, there is no single drug of choice that universally provides the best outcomes for all patients. Thus, it is critical for the health-care practitioner who treats pain to become familiar with the various subclasses, formulations, and modes of administration available for these agents and base decisions on clinical experience with the drug, prior patient experience, the availability of the formulation, and importantly cost and third-party coverage. All treatments should be viewed in the context of a treatment trial because it is not known a priori if the treatment will be effective. Opioids are classified according to the duration of their effect into long-acting, short-acting, and rapid-onset agents. Because the side effect profile of opioids is very individual, treatment of the opioid-naive patient usually begins with short-acting opioids to reduce the possibility of extended adverse effects. These agents are titrated over time until optimal analgesia is balanced with acceptable adverse effects. Short-acting agents are also useful as rescue medications among patients in whom longer-acting agents are being titrated to achieve acceptable analgesia. Even among patients in whom long-acting agents have been optimized, breakthrough pain that requires rescue medication may occur owing to increased activity related to the analgesic benefit of the long-acting agent. Thus, many patients require both long- and short-acting opioids for optimal round-the-clock analgesia. Some authorities suggest that opioid regimens should be merged or consolidated into long-acting agents given at defined intervals. This recommendation may improve patient compliance with opioid therapy and minimize risk for maladaptive behaviors, such as clock-watching, that often become apparent when short-acting agents are used exclusively. Although some patients benefit sufficiently from long-acting agents alone, others benefit from exclusive use of a short-acting regimen. Long-acting agents have also been recommended because of concerns about the rapid development of pharmacological tolerance when only short-acting opioids are used. Although this phenomenon has been demonstrated in animal studies, there is little evidence to extend these findings to humans. Surprisingly, there is no clear evidence that long-acting or extended-release opioid formulations provide better pain control than shortacting agents ( 15 ). Long-acting opioids themselves have varying characteristics that must be accounted for when prescribing. Evidence suggests that long-acting is a relative term; for example, certain preparations of long-acting morphine have a true duration of action of up to h ( 16,17 ), whereas others (such as certain preparations of morphine sulfate-controlled release and oxycodone-extended release) have been reported to provide sufficient analgesia for only 8 h despite FDA approval as agents that should be taken by mouth every 12 h ( 18 ). Similarly, methadone and levorphanol are commonly thought of as long-acting agents, but in clinical practice are often insufficient for more than a few hours of efficacy. For example, while methadone has a long elimination half-life, when used for as an analgesic, optimal analgesia may occur for appropriate patients when The American Journal of GASTROENTEROLOGY Supplements VOLUME 2 ISSUE 1 SEPTEMBER

5 The Use of Opioid Analgesics for Chronic Pain 7 dosed three or four times daily. This, however, may not be ideal for certain patients, as owing to the long elimination half-life of methadone, its pharmacodynamic effects besides analgesia, including sedation and the potential for respiratory depression, may linger for days. Thus, methadone should only be prescribed by those who have the skills required to do so in a safe manner. The fentanyl patch often needs to be changed every 48 h to provide sufficient pain relief. The long-acting opioid oxymorphone (Opana ER) is dosed every 12 h ( 19 ); similarly, the newly approved agent hydrocodone-extended release is formulated to provide analgesic coverage with twice daily dosing ( 20 ). A broad range of oral, short-acting opioids are commercially available, including but not limited to morphine sulfate (tablets and liquid formulations), hydromorphone, oxycodone (alone and in combination with acetaminophen, ibuprofen, or aspirin), hydrocodone (in combination with acetaminophen and ibuprofen), oxymorphone, and codeine. Rapid-onset opioids, such as oral transmucosal fentanyl citrate and fentanyl buccal tablets, are another option in select patients. Some opioid agents may have fewer opioid-related GI side effects, such as nausea, vomiting, and constipation. Transdermal formulations, particularly transdermal fentanyl, have been found to be associated with less frequent laxative use compared with morphine, an effect that is likely attributable to the nonoral route of administration ( ). Another option is the novel opioid tapentadol, which has demonstrated a lower incidence of GI-related side effects such as constipation. This μ -opioid agonist also inhibits the reuptake of norepinephrine, which is believed to augment its analgesic activity ( 25 ). Among patients with lower back pain, this agent at a dosage of mg twice daily provided similar efficacy as oxycodone HCl-controlled release at a dosage of mg twice daily, with the notable advantage that there were fewer GI side effects with tapentadol ( 26 ). As covered extensively elsewhere in this supplement, the peripheral μ -opioid antagonists, as well as lubiprostone, a bicyclic fatty acid derived from prostaglandin E1 that acts by specifically activating CIC-2 chloride channels on the apical aspect of GI epithelial cells, are useful adjuncts among patients who have opioid-induced constipation that cannot be resolved through more conservative measures. Abuse-deterrent opioids represent an option for patients at increased risk for opioid abuse ( 27 ). Long-acting oxymorphone (Opana ER) uses the Gr ü nenthal Group s INTAC technology that maintains the extended-release property while resisting crush. This formulation does not appear to influence the rate of absorption of the medication ( 19 ). In contrast, the generic version of oxymorphone ER has no such characteristics. Hydromorphone (Exalgo), includes an osmotically active bilayer core enclosed in a semipermeable tablet shell membrane that provides tamper-deterrent characteristics (28 ). This agent is approved only for opioid-tolerant patients (formally defined as patients who are chronically receiving opioid analgesics on a daily basis); use in opioid-naive patients could lead to an overdose and respiratory depression, death, or both, and should be used only for the treatment of chronic pain. Similarly, the package insert of the controlled-release formulation of oxycodone indicates that it is formulated with inactive ingredients intended to make the tablet more difficult to manipulate for misuse and abuse; this is the only agent that has received a true abuse-deterrent labeling ( 29 ). Regardless of which medication is selected, it is important to be cognizant of the potential for drug drug interactions in patients taking opioids, many of whom are taking multiple medications for the disease underlying the pain and / or comorbid conditions. Many opioids are metabolized by the cytochrome P450 system, particularly the CYP2D6 and CYP3A4 isoenzymes ( 30 ). These interactions have the potential to modulate the efficacy of treatment. WHEN SHOULD AN OPIOID EXIT STRATEGY BE CONSIDERED? As noted above, periodic reassessment is required to monitor progress, regression, and patient compliance. There are several reasons why an exit strategy may be considered. First, opioid therapy should be halted if there has been no convincing benefit from treatment despite reasonable attempts at dose adjustment, management of side effects, or switching among opioids ( 31 ). Second, consideration should be given to discontinue therapy in patients who fail to tolerate treatment or who present persistent compliance problems despite a patient treatment agreement and appropriate efforts at limit setting. Third, the presence of complicating comorbid conditions (including active substance abuse) may make opioid therapy more likely to harm than help an individual patient. The pathway chosen for an exit strategy is like all other aspects of opioid therapy highly individual. Among patients with no apparent addiction problem, gradual tapering over time with institution of nonopioid pain management (e.g., psychosocial support, cognitive-behavioral therapy, and / or nonopioid analgesics) is usually feasible. Among patients unable or unwilling to cooperate with an outpatient taper, it is often reasonable to provide sufficient opioid for a 1-month taper, or to maintain treatment until admission to an inpatient or outpatient program, as available. Among patients whose behavior is consistent with drug addiction, it is critical to promptly refer for addiction management. Never abandon a patient who has developed a substance abuse problem. CONCLUSIONS With appropriate attention, the opioids may be a powerful tool in the physician s pain management toolkit. When nonopioid treatments have provided insufficient relief or are contraindicated, it may be appropriate to consider a trial of opioid treatment. Most clinicians can point to specific examples where opioids were a safe and effective pain management modality that helped a specific patient recover function. There is no doubt that the opioids may be effective for chronic pain, yet without comprehensive assessment of the individual patient, careful management of underlying and comorbid conditions, and an evaluation of the potential risks 2014 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY Supplements

6 8 Argoff and Viscusi of prescribing these powerful agents, therapy may fail to provide adequate or temporally appropriate analgesia and may, in fact, elicit unnecessary side effects. The opioids also pose a well-known risk for respiratory depression as well as misuse, abuse, and diversion. Thus, tailoring therapy to the individual with chronic pain is critical and requires extensive knowledge of the available longacting, short-acting, and rapid-onset opioid preparations so that these can be used in a manner that best fits the individual needs of the individual patient. Pain is a dynamic phenomenon in that its characteristics and response to treatment evolve over time, as does the patient s general health state. Both positive and negative changes over time may necessitate a change in medication; for example, worsening comorbidities and additional medications may require dose modification or an outright switch to a different medication. On the other hand, effective pain management may permit marked increases in daily activity that elicits breakthrough pain, again requiring a modification in treatment regimen. Thus, periodic reassessment is required to monitor progress, regression, and patient compliance; in cases where no benefit is being obtained, a proactively formulated exit strategy should be considered. ACKNOWLEDGMENTS We thank John Ferguson for editorial assistance in preparing the manuscript for publication. CONFLICT OF INTEREST Guarantor of the article: Charles E. Argoff, MD. Specific author contributions: Argoff and Viscusi were equally instrumental in planning the review, interpreting the data, and drafting the manuscript. Both authors have seen and approved the final reports. Financial support: Viscusi has received grant support from AcelRx Pharmaceuticals, Cumberland Pharmaceuticals, and Pacira Pharmaceuticals. An independent medical education grant from Takeda Pharmaceuticals was provided to support the development of this supplement. The sponsor did not review the manuscript before publication nor did they provide input into the content of the supplement. Potential competing interests: Argoff has received consulting fees from AstraZeneca. Viscusi has received consulting fees from Ace1Rx, Cadence Pharmaceuticals, Cubist Pharmaceuticals, Pacira Pharmaceuticals, and Salix Pharmaceuticals, and also received lecture fees from Cubist Pharmaceuticals and Pacira Pharmaceuticals. REFERENCES 1. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Available at: edu/ ~ /media/files/report%20files/2011/relieving-pain-in-america-a- Blueprint-for-Transforming-Prevention-Care-Education-Research/Pain%2 0Research%202011%20Report%20Brief.pdf. Accessed 16 December C hou R, Fanc iu l l o G J, Fi ne P G et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009 ;10 : Weaver M, Schnoll S. Abuse liability in opioid therapy for pain treatment in patients with an addiction history. Clin J Pain 2002 ; 18 (Suppl 4) : C hab a l C, E r j ave c M K, Ja c ob s on L et al. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors. Clin J Pain 1997 ;13 : Manch i k ant i L, Pamp at i V, D am ron K S et al. Prevalence of opioid abuse in interventional pain medicine practice settings: a randomized clinical evaluation. Pain Physician 2001 ; 4 : Savage SR. Assessment for addiction in pain-treatment settings. Clin J Pain 2002 ;18 :S Katz N. Neuropathic pain in cancer and AIDS. Clin J Pain 2000 ; 16 : S Institute for Clinical Symptoms Improvement. Health care guideline: Assessment and management of chronic pain. Available at: icsi.org/_asset/bw798b/chronicpain.pdf. Accessed 16 June Hoffelt C, Zwack A. Assessment and management of chronic pain in patients with depression and anxiety. Ment Health Clin 2014 ; 4 : 55. Available at: Accessed 16 June, L eb ov it s A H. The psychological assessment of patients with chronic pain. Curr Rev Pain 2000 ; 4 : Hjermstad MJ, Fayers PM, Haugen DF et al. Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011 ;41 : G ou rl ay DL, He it HA, A l ma h re z i A. Un ive rs a l pre c aut i ons i n p ai n medicine: a rational approach to the treatment of chronic pain. Pain Med 2005 ;6 : G ou rl ay DL, He it HA. Un ive rs a l pre c aut i ons re v is ite d : manag i ng t he inherited pain patient. Pain Med 2009 ; 10 (Suppl 2) : S Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med 2005 ;6 : Argoff CE, Silvershein DI. A comparison of long- and short-acting opioids for the treatment of chronic noncancer pain: tailoring therapy to meet patient needs. Mayo Clin Proc 2009 ; 84 : Kadian [package insert]. Actavis Kadian LLC. Morristown, NJ Avinza [package insert]. King Pharmaceuticals, Inc. Bristol, TN MS Contin [package insert]. Purdue Pharma LP, Stamford, CT Opana ER [package insert]. Endo Pharmaceuticals Inc., Malvern, PA Zohydro ER [package insert]. Zogenix Inc R a dbr u ch L, S ab atow sk i R, L oi ck G. et al. Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine. Palliat Med 2000 ; 14 : Ahmedzai S, Bro oks D. Trans dermal fentanyl versus sustained-releas e oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS- Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997 ;13 : D on ne r B, Z e n z M, Tr y b a M et al. Direct conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer pain. Pain 1996 ;64 : Pay ne R, Mat h i as SD, Past a DJ et al. Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol 1998 ;16 : Kress HG. Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon? Eur J Pain 2010 ;14 : Buy na k R, Shapi ro DY, Ok amoto A et al. E fficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. Exp Opin Pharmacother 2010 ;11 : Mo or man - L i R, Mot yck a C A, Inge L D et al. A review of abuse-deterrent opioids for chronic nonmalignant pain. P T 2012 ;37 : Exalgo [package insert]. Mallinckrodt LLC. Hazelwood, MO Oxycontin [package insert]. Purdue Pharma LLP. Stamford, CT Knotkova H, Fine PG, Portenoy RK. Opioid rotation: the science and the limitations of the equianalgesic dose table. J Pain Symptom Manage 2009 ;38 : Verloop WL, Voskuil M, Doevendans PA. Renal denervation: a new treatment option in resistant arterial hypertension. Neth Heart J 2013 ;21 : Passik SD, Portenoy RK, Ricketts PL. Substance abuse issues in cancer patients. Part 1: Prevalence and diagnosis. Oncology (Williston Park) 1998 ;12 :517 21, Passik SD, Portenoy RK, Ricketts PL. Substance abuse issues in cancer patients. Part 2: Evaluation and treatment. Oncology (Williston Park) 1998 ;12 : ; discussion 736, This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit org/licenses/by-nc-nd/3.0/ The American Journal of GASTROENTEROLOGY Supplements VOLUME 2 ISSUE 1 SEPTEMBER