Ensuring Patient Protections When Tapering Opioids: Consensus Panel Recommendations.

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

Challenges with Implementing the Centers for Disease Control and Prevention Opioid Guideline: A Consensus Panel Report.

BACKGROUND: A national crisis of opioid-related morbidity, mortality, and misuse has led to initiatives to address the appropriate role of opioids to treat pain. Deployment of a guideline from the Centers for Disease Control and Prevention to reduce the risks of opioid therapy has raised substantial clinical and public policy challenges. The agency anticipated implementation challenges and committed to reevaluating the guideline for intended and unintended effects on clinician and patient outcomes. OBSERVATIONS: A multidisciplinary expert panel met to review the influence of the core recommendations of the guideline on pain management practices, principally regarding the estimated 5 to 8 million Americans with chronic pain currently on opioids. The panel identified implementation challenges, including application of dosage ceilings and prescription duration guidance, failure to appreciate the importance of patient involvement in decisions to taper or discontinue opioids, barriers to diagnosis and treatment of opioid use disorder, and impeded access to recommended comprehensive, multimodal pain care. Furthermore, policy-making and regulatory bodies may misapply guideline recommendations without flexibility and, sometimes, without full awareness of what the guideline contains. CONCLUSIONS AND RELEVANCE: The panel largely supported the guideline, endorsing its focal points of safety and comprehensive assessment and monitoring. To mitigate clinical and policy challenges identified with implementing the guideline, the panel discussed areas where viewpoints diverged and arrived at consensus proposals. The target audience includes the leaders and institutions that create policy and influence guideline implementation to include regulatory agencies, legislators, public and private payers, and health care systems.

Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations.

Objective: To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. Methods: An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Results: Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous UDM. Urine drug monitoring is suggested to be performed at baseline for most patients prescribed opioids for chronic pain and at least annually for those at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk. Additional UDM should be performed as needed on the basis of clinical judgment. Conclusions: Although evidence on the efficacy of UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is recommended by the panel as part of ongoing comprehensive risk monitoring in patients prescribed opioids for chronic pain.

Strategies for Combating Opioid-Induced Constipation: Targeted Mechanisms to Maintain Pain Control Without Compromise.

Opioid-induced constipation (OIC) is a common side effect of opioid use and can occur from the outset of opioid therapy (Online access: http://courses.elseviercme.com/aapmr2016/638e). OIC has been reported to interfere with pain management, increase health care costs, decrease work productivity and daily activities, and significantly affect patient quality of life. It can also lead to bowel obstruction. Assessing and managing OIC is important for establishing maximum function for patients. Several pharmacologic approaches, with different mechanisms of action, are available or in development.

Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation.

OBJECTIVE: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. METHODS: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique. RESULTS: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation. CONCLUSIONS: The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions.

Ethnicity and interdisciplinary pain treatment.

OBJECTIVE: The purpose of this study was to identify ethnic differences in interdisciplinary pain treatment outcome and whether these differences occur while controlling for the effects of demographics, psychosocial, and secondary gain. METHODS: We assessed a sample of 116 (Caucasian, African American, and Latino/a) chronic pain patients who participated a 4-week interdisciplinary pain treatment program. Outcome measure included pretreatment, post-treatment, and change scores on the Multidimensional Pain Inventory, Pain Anxiety Symptom Scale 20, Chronic Pain Acceptance Questionnaire, Coping Strategies Questionnaire-revised, and the Center for Epidemiologic Studies Depression Scale-short form. RESULTS: Analysis of covariances revealed that after accounting for educational and sex differences, ethnic minorities differed from Caucasians on a number of treatment outcome measures at pre- and post-treatment [F's ≥ 5.38; P's < 0.01]. At pretreatment, Latino/a's endorsed greater levels of pain-related anxiety, pain severity, and pain catastrophizing than Caucasians. Both Latino/a's and African Americans reported greater use of prayer at pre- and post-treatment, with Caucasians showing the greatest decrease in the use of prayer in response to treatment. At post-treatment, African Americans had higher level of depression and lower levels of reported activity than Caucasians. CONCLUSIONS: Results support the notion that ethnic differences in pain treatment outcome exist. Further, ethnic minority groups appear to have greater levels of distress compared to Caucasians. However, African Americans, Latino/a's and Caucasians demonstrated similar improvements on all outcome measures, with exception of the use of prayer. Future studies should begin to explore the mechanisms to explain why ethnic group differences in pain treatment outcome occur.

Validity testing of patient objections to acceptance of tamper-resistant opioid formulations.

BACKGROUND: Tamper-resistant formulations (TRFs) of oral opioid drugs are intended to prevent certain types of abuse (eg, intranasal, intravenous). Patients raising objections to receiving a TRF may have valid concerns or may be seeking a formulation that can be more easily misused. METHODS: US clinicians experienced in pain management met in October 2011 to discuss common patient objections to being switched from a non-TRF opioid to a TRF of the same opioid. Retail pharmacy, health insurance, and scientific data were used to assess the potential validity of these patient objections. RESULTS: Clinical experience switching patients from a non-TRF to a TRF opioid was limited to oxycodone controlled release (CR), as it was the only TRF available at that time; knowledge of other TRFs was limited to the scientific literature. Common objections from patients included "costs more," "not covered by insurance," "can't feel it working," and "causes adverse events." Objective retail pharmacy and insurance coverage information for oxycodone CR was accessible and indicated that patient objections were based on cost and coverage varied by insurer. Unpublished trial results (ClinicalTrials.gov) revealed that TRF oxycodone CR has a slower initial release than the non-TRF formulation, which may reduce positive subjective effects. The complaint "I can't feel it working" may reflect lessened positive subjective effects rather than reduced analgesic efficacy. Most tolerability complaints lacked objective support. CONCLUSION: The general process used to assess the validity of patient objections to TRF oxycodone CR may be applied to other TRFs once they become available. Publication of clinical data on TRFs would help clinicians to appropriately weigh patient concerns.

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs.

Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events.

Topical therapies in the management of chronic pain.

Chronic pain, whether localized or generalized, is a widespread, often debilitating condition affecting > 25% of adults in the United States. Oral agents are the cornerstone of chronic pain treatment, but their use may be limited in certain patients, particularly the elderly. Topical therapies offer advantages over systemically administered medications, including the requirement of a lower total systemic daily dose for patients to achieve pain relief, site-specific drug delivery, and avoidance of first-pass metabolism, major drug interactions, infections, and systemic side effects. Several types of topical agents have been shown to be useful in the treatment of patients with chronic pain. Both capsaicin and topical diclofenac have been shown to be effective in the treatment of patients with chronic soft-tissue pain. In patients with hand and knee osteoarthritis (OA), the American College of Rheumatology generally recommends oral treatments (acetaminophen, oral nonsteroidal anti-inflammatory drugs [NSAIDs], tramadol, and intra-articular corticosteroids) and topical NSAIDs equally, favoring topical agents only for patients who have pre-existing gastrointestinal risk or are aged ≥ 75 years. Topical NSAIDs have been shown to provide relief superior to that of placebo and comparable to that of oral ibuprofen. Similarly, ketoprofen gel has been shown to be superior to placebo and similar to oral celecoxib in reducing pain in patients with knee OA. Different formulations of topical diclofenac (including the diclofenac hydroxyethyl pyrrolidine patch, diclofenac sodium gel, and diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide USP) have been shown to be superior to placebo and comparable to oral diclofenac in the treatment of patients with pain due to knee OA, with a lower incidence of gastrointestinal complaints than with the oral formulation. In patients with neuropathic pain, topical forms of both capsaicin and lidocaine have been shown to be useful in the treatment of postherpetic neuralgia and diabetic peripheral neuropathic pain. Lidocaine has also demonstrated efficacy in relieving patient pain due to complex regional pain syndrome and may be useful in the treatment of patients with neuropathic pain who have cancer, although clinical trial results have not been consistent. Data suggest that topical therapies may offer a safe, well-tolerated, and effective alternative to systemic therapies in the treatment of patients with chronic, localized musculoskeletal and neuropathic pain.

Treatment outcomes for workers compensation patients in a U.S.-based interdisciplinary pain management program.

OBJECTIVES: Assess the efficacy of an outpatient-based interdisciplinary pain rehabilitation program for patients with active workers compensation claims. PATIENTS: Data were available for 101 patients, primarily with chronic low back pain (75%), who participated in the program. METHODS: Treatment included a 4-week (Monday to Friday), 8-hours/day graded progressive program that included individual and group therapies (pain psychology, physical therapy, occupational therapy, relaxation training/biofeedback, aerobic conditioning, pool therapy, vocational counseling, patient education and medical management). Outcome measures included program completion status, release-to-work status, return-to-work status, total scores on the Beck depression inventory, state-trait anxiety inventory, pain catastrophizing scale, and the McGill pain questionnaire visual analogue scale (MPQ VAS). The majority of the patients (65%) graduated from the program. Pre-postoutcome data were available for those who graduated from the program. For noncompleters, last obtained MPQ VAS was compared with their initial MPQ VAS scores. RESULTS: Of those completing the program, most patients (91%)were released to return to work; with 80% released to full-time status and 11% released to gradual return. Approximately half (49%) of the program completers returned to work. Paired-samples t-tests showed that program completers had significant reductions in depression (P = 0.000), pain-related catastrophizing (P = 0.033), and pain intensity (P = 0.000), but not in anxiety (P = 0.098). Interestingly, the last obtained (at early discharge/withdrawal) pain intensity scores (M = 70.33) were higher than at baseline (M = 61.20) in the noncompleters. This difference was not statistically significant (P = 0.127) but may be clinically meaningful. DISCUSSION: Our results support the efficacy of an outpatient-based 4-week interdisciplinary pain rehabilitation program in decreasing emotional distress, reducing pain intensity, and improving return-to-work status in the majority of completers in this challenging population. Patients reporting increased pain at discharge or those discharged early may have been due to operant factors.

Strategies to reduce the tampering and subsequent abuse of long-acting opioids: potential risks and benefits of formulations with physical or pharmacologic deterrents to tampering.

Increased prescribing of opioid analgesics for chronic noncancer pain may reflect acceptance that opioid benefits outweigh risks of adverse events for a broadening array of indications and patient populations; however, a parallel increase in the abuse, misuse, and diversion of prescription opioids has resulted. There is an urgent need to reduce opioid tampering and subsequent abuse without creating barriers to safe, effective analgesia. Similar to the "magic bullet" concept of antibiotic development (kill the bacteria without harming the patient), the idea behind reformulating opioid analgesics is to make them more difficult to tamper with and abuse by drug abusers but innocuous to the compliant patient. As antibiotics exploit differences in bacterial and human physiology, tamper-resistant formulations depend on differences in the way drug abusers and compliant patients consume opioids. Most opioid abusers tamper with tablets to facilitate oral, intranasal, or intravenous administration, whereas compliant patients usually take intact tablets. Pharmaceutical strategies to deter opioid abuse predominantly focus on tablet tampering, incorporating physical barriers (eg, crush resistance) or embedded chemicals that render tampered tablets inert, unusable, or noxious. Deterring tampering and abuse of intact tablets is more challenging. At present, only a few formulations with characteristics designed to oppose tampering for abuse have received approval by the US Food and Drug Administration, and none has been permitted to include claims of abuse deterrence or tamper resistance in their labeling. This review discusses the potential benefits, risks, and limitations associated with available tamper-resistant opioids and those in development.