Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse.PerspectiveCurrently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.     

Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence,in Collaboration With the Heart Rhythm Society

Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence.PerspectiveThis guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.     

The use of long-acting opioids in chronic pain management

The consensus statement from the American Pain Society and American Academy of Pain Medicine states that the undertreatment of pain is unjustified [6]. It has been suggested that opioid therapy can be used effectively to treat noncancer pain in a subset of patients [26], and this is becoming more acceptable [3]. Providing sustained analgesia is an important aspect of therapy, and medications should be administered on an around-the-clock basis, because regular administration of doses maintains a constant level of drug in the body and helps prevent recurrence of pain. Ideal treatment for persistent pain is a long-acting opioid administered around the clock to prevent baseline pain, with the use of short-acting opioids as supplemental agents for breakthrough pain. Controlled-release formulations can lessen the inconvenience associated with around-the-clock administration of short-acting opioids. Sustained analgesia also can be achieved with transdermal fentanyl, which combines a strong opioid with a 72-hour release profile and the benefits of a parenteral route, avoiding first-pass metabolism. Controlled-release formulations of morphine and oxycodone are available in the United States, and hydromorphone preparations are being reviewed for approval. Clinical experience with these formulations and transdermal fentanyl indicates that these agents are equally effective in controlling pain. Studies have demonstrated improved quality of life with the transdermal route and with controlled-release morphine and oxycodone. Because of patch reapplication every 72 hours, the transdermal route also enhances compliance. Use of an opioid without the need for oral or intravenous administration and the opportunity to improve compliance are among the advantages of the transdermal route in clinical practice. The nurse has an important role in the management of patients receiving long-acting opioids for chronic noncancer pain, Facilitation of the conversion from short-acting to long-acting opioids may be the initial step. Individualization of therapy to determine which route and product best suits the patient's needs and lifestyle can be accomplished through a comprehensive nursing assessment. Titration of dose along with institution of a short-acting opioid for break-through pain may require frequent interventions that a nurse familiar with the patient can provide. Prevention and management of opioid-related adverse events are essential for effective opioid therapy. Providing patient and family education regarding administration, monitoring, and management of opioid therapy is an important nursing role. Lastly, documentation of pain level, functional status, and opioid-related adverse events is required for each contact with the patient, to make this information available to all who assist in the management of the patient's pain. Chronic noncancer pain is an experience that affects all aspects of a patient's life. Effective pain management with long-acting opioids may help the patient to focus on the positive aspects of life, decreasing the focus on pain.     

Variable Use of Opioid Pharmacotherapy for Chronic Noncancer Pain in Europe: Causes and Consequences

ABSTRACT.?

According to the 2005 Pain in Europe Survey, the use of opioids to treat patients with chronic noncancer pain varies considerably among different countries in Europe. Undertreatment of chronic pain is common. This review examines the possible causes and consequences of limiting opioid availability to these patients. The causes of inadequate opioid use include medical, ethical, and cultural factors that influence prescribing decisions; legislative and health care system controls that serve to restrict the use of opioids for long-term treatment of non–cancer-related pain conditions; and poor treatment acceptance by patients. The validity of these restrictions is discussed in relation to the need to protect patients and society from harm due to adverse events, and the potential for misuse and abuse with prescribed opioids. This is balanced against the therapeutic goal of providing the best available pain-relieving treatment and to avoid the consequences of unnecessary suffering in patients with chronic noncancer pain.     

Clinician Beliefs About Opioid Use and Barriers in Chronic Nonmalignant Pain

A survey of the medical directors of multidisciplinary pain clinics and multidisciplinary pain centers listed in the American Pain Society Pain Facilities Directory was conducted to define those pain specialists' beliefs about the role of opioid analgesia in 14 types of chronic nonmalignant pain. Respondents also reported their perceptions of barriers to their prescribing opioids for chronic nonmalignant pain and what they perceived as barriers to opioid prescribing for chronic nonmalignant pain by other, non-pain specialist clinicians in their communities. The respondents are characterized by demographics, disciplines, specialties, and time in practice. The percentage of time that a pharmacist was available in the pain programs also is reported. There is increasing acceptance of opioids for most of the listed types of chronic nonmalignant pain, but the acceptance varies by types of pain syndromes. Opioids were most consistently accepted for sickle cell disease pain and least commonly endorsed for headaches, myofascial pain, and fibromyalgia. Factors that may influence clinicians' perceptions about opioids are discussed.     

Benefits of Extended-Release Opioid Analgesic Formulations in the Treatment of Chronic Pain

Chronic noncancer pain represents a major health problem that affects many patients, resulting in suffering, reduced productivity, and substantial health care costs. The patient with chronic noncancer pain is burdened by decreased quality of life, decreased sleep, interference with social relationships, diminished cognitive functions, interference with activities of daily living, decreased productivity, and increased anxiety and depression. A survey examining the burden of pain on health and productivity found decreases of 45% in physical health and 23% in mental health at a cost of $61.2 billion per year in productive work time. An American Pain Society survey of 800 patients with moderate to severe chronic pain reported that 47% felt their pain was not under control. The goal of pharmacological therapy for chronic noncancer pain is to provide sustained analgesia. Chronic pain management guidelines recommend the use of long-acting, extended-release (ER) analgesics because they provide prolonged, more consistent plasma concentrations of drug compared with short-acting agents, thus minimizing fluctuations that could contribute to end-of-dose breakthrough pain. ER analgesics offer more consistent and improved nighttime pain control, less need to awaken at night to take another dose of pain medication, and less clock-watching by patients in chronic noncancer pain. Among the available ER opioids, tramadol ER possesses a unique mechanism of action, making it a viable opioid of first choice for patients suffering from a variety of chronic noncancer pain conditions, such as osteoarthritis, low back pain, and neuropathic pain.     

Chronic noncancer pain rehabilitation with opioid withdrawal: comparison of treatment outcomes based on opioid use status at admission

OBJECTIVE: To study differences in treatment outcomes between patients with chronic noncancer pain taking vs those not taking maintenance opioids at admission to a pain rehabilitation program. PATIENTS AND METHODS: A nonrandomized 2-group prepost design was used to compare 356 patients admitted to the Mayo Comprehensive Pain Rehabilitation Center from January 2002 to December 2002 at admission and discharge by opioid status at admission. Measures of pain severity, interference due to pain, perceived life control, affective distress, activity level, depression, and catastrophizing (an exaggerated negative mental set associated with actual or anticipated pain experiences) were used to compare opioid and nonopioid groups. The patients entered a 3-week intensive outpatient multidisciplinary pain rehabilitation program designed to improve adaptation to chronic noncancer pain. The program uses a cognitive-behavioral model and incorporates opioid withdrawal. RESULTS: More than one third of patients (135/356) were taking opioids daily at admission. At completion of the program, all but 3 of the 135 patients had successfully discontinued opioid treatment. No significant pretreatment differences were found between the opioid and nonopioid group regarding demographics, pain duration, treatment completion, or all outcome variables, including pain severity. Significant improvement was noted at discharge for all outcome variables assessed regardless of opioid status at admission. CONCLUSION: Patients with symptomatically severe and disabling pain while taking maintenance opioid therapy can experience significant improvement in physical and emotional functioning while participating in a pain rehabilitation program that incorporates opioid withdrawal.     

European Pain Federation (EFIC) position paper on appropriate use of cannabis‐based medicines and medical cannabis for chronic pain management

Cannabis‐based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis‐based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis‐based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis‐based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline‐recommended first‐ and second‐line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis‐based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non‐neuropathic noncancer pain), the use of cannabis‐based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis‐based medicines should be terminated.

Significance

This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis‐based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients.     

Intrathecal Drug Administration in Chronic Pain Syndromes

Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long‐term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo‐controlled trials. A randomized study showed this treatment option to be effective over a short follow‐up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drug administration in patients suffering from cancer‐related pain is more compelling than that of chronic noncancer pain.     

A Review of Potential National Chronic Pain Surveillance Systems in the United States

Pain has been established as a major public health problem in the United States (U.S.) with 50 million adults experiencing chronic pain and 20 million afflicted with high-impact chronic pain (ie, chronic pain that interferes with life or work activities). High financial and social costs are associated with chronic pain. Over the past 2 decades, pain management has been complicated by the marked increase in opioids prescribed to treat chronic noncancer pain and by the concurrent opioid crisis. Monitoring the prevalence of chronic pain and pain management is especially important because pain management is changing in uncertain ways. We review potential U.S. chronic pain surveillance systems, present potential difficulties of chronic pain surveillance, and explore how to address chronic pain surveillance in the current opioid era. We consider case definitions, severity, anatomic site, and varieties of chronic pain management strategies in reviewing and evaluating national surveys for chronic pain surveillance. Based on the criteria evaluated, the National Health Interview Survey offers the best single source for pain surveillance as the pain-related questions administered are brief, valid, and cover a broad scope of pain-related phenomena.PerspectiveThis review article describes data sources that can be leveraged to conduct national chronic pain surveillance in the United States, explores case defining or pain-related questions administered, and evaluates them against 8 surveillance attributes.     

Rediscovery of Methadone to Improve Outcomes in Pain Management

Clinically, methadone is most known for its use in the treatment of opioid maintenance therapy. However, methadone's pharmacological profile makes it an excellent analgesic that can enhance acute and chronic pain management. It is a potent μ-receptor agonist with a longer elimination half-life than most clinically used opioids. In addition, methadone inhibits serotonin and norepinephrine uptake, and it is an N-methyl-D-aspartate antagonist. These distinct analgesic pathways mediate hyperalgesic, allodynic, and neuropathic pain. Its unique analgesic properties provide several essential benefits in perioperative use, neuropathic pain, cancer, and noncancer pain. Despite these proven clinical utilities, methadone has not been used widely to treat acute and chronic pain in opioid naïve patients. This article describes the unique pharmacology of methadone and provides emerging evidence to support its application in acute and chronic pain management. Pain management options and guidelines for surgical patients on methadone are discussed as well.     

Chronic opioid therapy for chronic noncancer pain: How can the scales predict outcome without a good SMACK?

Chronic opioid therapy presents potential benefits to the patient with chronic noncancer pain. Clearly, chronic opioid therapy has risks such as misuse, abuse, and diversion. Screening tools have been developed to define patients at risk for, predict, and detect these negative outcomes. Careful study demonstrates that the tools and their application in clinical practice are imperfect and often fail to fulfill their promise. Barriers to their success range from limited psychometric capabilities to the presence of confounding psychiatric comorbidities. However, the essence of poor outcome in the care of patients with chronic noncancer pain is the inexperience of the practitioner with chronic opioid therapy and the lack of a comprehensive approach to case formulation. The care of patients can only reach its full potential if practitioners follow a standardized approach repeatedly with ongoing reflection about why a particular outcome occurred, what they could do differently, and how a coherent evidence-based rationale supports their recommendations. This iterative process will refine clinical practice and produce experts in pain management.     

Adherence Monitoring with Chronic Opioid Therapy for Persistent Pain: A Biopsychosocial-Spiritual Approach to Mitigate Risk

Opioids represent a mainstay in the pharmacologic management of persistent pain. Although these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing “Position Statement on Pain Management in Patients with Substance Use Disorders” (2012) focuses on the intersection of persistent pain, substance use disorder (SUD), and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care.     

Opioids,Chronic Pain,and Addiction in Primary Care

Research has largely ignored the systematic examination of physicians' attitudes towards providing care for patients with chronic noncancer pain. The objective of this study was to identify barriers and facilitators to opioid treatment of chronic noncancer pain patients by office-based medical providers. We used a qualitative study design using individual and group interviews. Participants were 23 office-based physicians in New England. Interviews were audiotaped, transcribed, and systematically coded by a multidisciplinary team using the constant comparative method. Physician barriers included absence of objective or physiological measures of pain; lack of expertise in the treatment of chronic pain and coexisting disorders, including addiction; lack of interest in pain management; patients' aberrant behaviors; and physicians' attitudes toward prescribing opioid analgesics. Physician facilitators included promoting continuity of patient care and the use of opioid agreements. Physicians' perceptions of patient-related barriers included lack of physician responsiveness to patients' pain reports, negative attitudes toward opioid analgesics, concerns about cost, and patients' low motivation for pain treatment. Perceived logistical barriers included lack of appropriate pain management and addiction referral options, limited information regarding diagnostic workup, limited insurance coverage for pain management services, limited ancillary support for physicians, and insufficient time. Addressing these barriers to pain treatment will be crucial to improving pain management service delivery.