Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment.     

Critical issues on opioids in chronic non-cancer pain: an epidemiological study

The aim of the study was epidemiologically to evaluate the long-term effects of opioids on pain relief, quality of life and functional capacity in long-term/chronic non-cancer pain. The study was based on data from the 2000 Danish Health and Morbidity Survey. As part of a representative National random sample of 16,684 individuals (>16 years of age), 10,066 took part in an interview and completed a self-administered questionnaire. Cancer patients were excluded. The interview and the self-administered questionnaire included questions on chronic/long-lasting pain (>6 months), health-related quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use of anxiolytics and antidepressants and pain intensity. Pain relief, quality of life and functional capacity among opioid users were compared with non-opioid users. Opioid usage was significantly associated with reporting of moderate/severe or very severe pain, poor self-rated health, not being engaged in employment, higher use of the health care system, and a negative influence on quality of life as registered in all items in SF-36. Because of the cross-sectional nature causative relationships cannot be ascertained. However, it is remarkable that opioid treatment of long-term/chronic non-cancer pain does not seem to fulfil any of the key outcome opioid treatment goals: pain relief, improved quality of life and improved functional capacity.     

10-year follow-up of chronic non-malignant pain patients: opioid use, health related quality of life and health care utilization.

BACKGROUND: In Denmark, opioids have been used liberally for many years in the treatment of non-malignant pain, but long-term consequences as tolerance and influence on health related quality of life remain unknown. AIM: Adherence to medical treatment, opioid dose escalation, health related quality of life, anxiety, depression, coping strategies and health care utilization were evaluated in chronic pain patients 10 years after treatment in a multidisciplinary pain centre. METHODS: Information was gathered from medical records, postal questionnaires and a central hospital register. RESULTS: Opioid dose escalation occurred in only a few patients. Increase and decrease in opioid dose were almost equally frequent. Sixty percent of those discharged on long acting opioids were still on that treatment at follow-up. Twenty-eight percent of the patients initiated opioid treatment after discharge from the pain centre. Occupational status was identified as a determining factor for future opioid use. Opioid users had a lower health related quality of life, higher occurrence of depression and more frequent use of coping strategies like 'Catastrophizing' and 'Hoping and Praying'. Adjuvant analgesics were highly discontinued. Multidisciplinary pain treatment reduced the number of hospital admissions and in-hospital days. CONCLUSION: We recommend that future research on opioid treatment does not only focus on biological issues. The effect of opioids needs to be viewed in a much more complex context where consequences like health related quality of life, depression and the role of various coping strategies are included.     

Impact of opioid use on outcomes of functional restoration

OBJECTIVES: To examine the effect of opioid use on psychological function, physical functioning, and return-to-work outcomes of a multidisciplinary rehabilitation program (MRP) for chronic pain. METHODS: The participants were 127 patients with on-the-job injuries who had completed an MRP between 2001 and 2003. Opioid use was controlled by the patients' treating physicians (who were not affiliated with the MRP) and was assessed via patient self-report at the time of admission to the program and discharge. Other measures included pretreatment and posttreatment assessments of depression, pain severity, perceived disability, and physical ability (floor-to-waist lifting capacity). Return-to-work outcomes were obtained via follow-up phone calls approximately 6 months posttreatment. RESULTS: Significant improvements from pretreatment to posttreatment were evidenced on all psychological and physical measures for both opioid users and nonusers. Further, there were no significant posttreatment differences between opioid and nonopioid users on psychological, physical, or return-to-work outcomes. DISCUSSION: The role of opioids in the treatment of chronic pain continues to be controversial. Despite a lack of definitive data on their effectiveness, opioids continue to be prescribed, and thus patients using opioids continue to present for multidisciplinary rehabilitation. Although further exploration is warranted, results of the current study suggest that opioid use during rehabilitation does not necessarily preclude treatment success.     

Disease-specific and generic health outcomes: a model for the evaluation of long-term intrathecal opioid therapy in noncancer low back pain patients.

OBJECTIVE: The present study provided comprehensive characterization of the long-term outcomes of intrathecal opioid administration via a drug administration system (DAS) in chronic pain patients with predominantly low back pain. A conceptual framework based on multidimensional outcomes is proposed using both disease-specific and generic measures. DESIGN: Pre-post longitudinal data were collected in a retrospective fashion on 38 patients receiving intraspinal opioid therapy for a minimum of 36 months (average = 50 months). MAIN OUTCOME MEASURES: Disease-specific measures included magnitude of infused opioid, side effects/complications, pain ratings, McGill Pain Questionnaire, Beck Depression Inventory, Oswestry Disability Questionnaire, and patient estimated improvement in pain (0-100%). Generic measures of health included the Quality of Well-Being Scale, Medical Outcomes Study (MOS) Short Form 36 (SF-36), return to work, patient estimated improvement in functioning, overall patient satisfaction, and family opinion of patient improvement. RESULTS: Disease-specific outcomes. Patients receiving long-term intrathecal opioid administration showed a sixfold increase in morphine equivalents infusion rates across time. DAS patients showed a small but significant decrease in pain ratings from pre-treatment levels. Following 3 years or more of intrathecal opioid infusion, patients endorsed high pain levels on the McGill Pain Questionnaire, severe levels of disability via the Oswestry Disability Questionnaire, mild levels of depression based on the Beck Depression Inventory, and multiple side effects associated with the intrathecal opioids and complications related to the infusion system. On retrospective questioning, patients receiving long-term intrathecal opioid administration reported an average of 64% improvement in their pain and 48% improvement in functioning. Family members of patients reported that they observed on average a 61% improvement in patient's pain. Generic outcome measures. On the Quality of Well-Being Scale, patients reported significantly lower health-related quality of life than health maintenance organization enrollees with no known chronic condition and patients with rheumatoid arthritis (p < 0.001). On the MOS SF-36, patients reported significantly lower physical functioning than the U.S. general population, patients with uncomplicated medical conditions, diabetes-type II patients, and congestive heart failure patients. Mental functioning was comparable to the U.S. general population (p > 0.001). Fourteen percent of patients were working following implantation. Eighty-nine percent of patients reported good to excellent satisfaction with the long-term intrathecal opioid therapy. CONCLUSIONS: Results from this study revealed differences in findings across the outcome measures, highlighting the complexity of intrathecal opioid therapy. Generally, patients after 3 years or more of intrathecal opioid therapy can be characterized as hav ing substantially impaired physical functioning with a high prevalence of side effects. Despite poor physical functioning, patients endorsed relatively good mental health status with only mild depressive symptoms. Longitudinal pain ratings showed a modest decrease from pretreatment levels. On retrospective evaluation, patients and their family endorsed high levels of pain relief secondary to intrathecal therapy. Overall, findings support that intrathecal opioid therapy provides some therapeutic benefit although substantial physical impairment continues to cause debilitation in the patient population.     

A population-based study on chronic pain and the use of opioids in Portugal

Although increasing doubts exist regarding the long-term effectiveness and safety of opioids in patients with chronic pain (CP), most guidelines still recognize opioids as an option in effective management of CP. We aimed to describe the prevalence and factors associated with opioid use in subjects with CP in Portugal and to evaluate satisfaction and self-assessed treatment effectiveness. A nationwide study was conducted in a representative sample of the adult Portuguese population. The 5094 participants were selected using random digit dialing and estimates were adequately weighted for the population. The prevalence of opioid use by subjects with CP was 4.37% (95% confidence interval [CI] 3.4–5.5); and in subjects experiencing CP with and without cancer, it was 10.13% and 4.24%, respectively. Use of strong opioids was reported by only 0.17% of CP subjects. Sex, pain severity and symptoms of depression and anxiety were significantly associated with opioid use; however, in multivariate modeling, only pain-related disability remained significant. No significant differences among users and nonusers of opioids were observed regarding treatment satisfaction and self-assessed effectiveness. Although extremely high rates of use of opioids exist in a few countries, it should not be seen as a ubiquitous problem. Indeed, we showed that in Portugal, as in many other regions in the world, opioids are used much less frequently than in those few countries. Moreover, we did not find significant differences among users and nonusers of opioids regarding satisfaction and self-assessed effectiveness, eventually showing the results to be in line with reports that show doubt about opioids’ effectiveness. Further research and particular attention to and continuous monitoring of the trends of use and abuse of opioids worldwide are recommended.     

Management of chronic noncancer pain in the primary care setting

While opioids are regarded as the mainstay of chronic pain management, their use is controversial in the minds of many primary care physicians due to clinical concerns about dependence, abuse, and addiction and medicolegal concerns regarding state and federal regulatory authorities. For patients with moderate to moderately severe pain, the treatment of choice is a long-acting opioid or opioid combination drug product to provide sustained analgesia along with improvements in sleep quality, compliance, and possibly quality of life. Careful screening of patients being considered for long-term opioid therapy with validated questionnaires can identify patients who may have difficulties in managing opioids. These patients should not be denied access to opioid therapy, but they do require focused monitoring and case management. Ongoing monitoring should focus on the 4 A's (ie, analgesia, activities of daily living, adverse effects, and aberrant drug-related behaviors), and all aspects of patient care must be thoroughly documented.     

épidémiologie croisée entre conduites addictives et douleurs chroniques : une revue de la littérature

Even though opioids have been used for pain for thousands of years, opioid therapy for chronic non-cancer pain is controversial due to concerns regarding the long-term effectiveness and safety, particularly the risk of addiction, both in patients and medical community. The numerous studies published still remain controversial. This article reviews on the one hand the meta-analysis, systematic reviews and studies on the use of opioids in chronic pain and the risk of addiction, and on the second hand the few data dealing with the prevalence of chronic non-cancer pain among patients being treated for substance use disorders.     

Patterns of opioid use for chronic noncancer pain in the Veterans Health Administration from 2009 to 2011

Although opioids are frequently prescribed for chronic noncancer pain (CNCP) among Veterans Health Administration (VHA) patients, little has been reported on national opioid prescribing patterns in the VHA. Our objective was to better characterize the dosing and duration of opioid therapy for CNCP in the VHA. We analyzed national VHA administrative and pharmacy data for fiscal years 2009 to 2011. For individuals with CNCP diagnoses and any opioid use in the fiscal year, we calculated the distribution of individual mean daily opioid dose, individual total days covered with opioids in a year, and individual total opioid dose in a year. We also investigated the factors associated with being in the top 5% of individuals for total opioid dose in a year, which we term receipt of high-volume opioids. About half of the patients with CNCP received opioids in a given fiscal year. The median daily dose was 21 mg morphine equivalents. Approximately 4.5% had a mean daily dose higher than 120 mg morphine equivalents. The median days covered in a year was 115 to 120 days in these years for those receiving opioids. Fifty-seven percent had at least 90 days covered with opioids per year. Major depression and posttraumatic stress disorder were positively associated with receiving high-volume opioids, but nonopioid substance use disorders were not. Among VHA patients with CNCP, chronic opioid therapy occurs frequently, but for most patients, the average daily dose is modest. Doses and duration of therapy were unchanged from 2009 to 2011.     

Are opioids effective in relieving neuropathic pain?

The purpose of this review is to identify important issues and to review the data that underlie the controversial effectiveness of opioids in relieving neuropathic pain. This controversy seems related to the use of multiple definitions of neuropathic pain together with its distinct mechanisms in both experimental animal models and human neuropathic pain syndromes, methodological shortcomings in available randomized controlled clinical trials, different methods of pain assessment, the inappropriate use of terms like efficacy and responsiveness, differential responses in spontaneous versus evoked pains, interindividual differences to specific opioids and opioid doses, and duration of follow-up. New randomized controlled clinical trials with opioids in neuropathic pain are still needed. These studies should include larger patient samples with rigorously defined homogeneous neuropathic pain syndromes. Active placebo's mimicking side-effects should be included in the double-blind design, and control of unmasking should be performed. Individual titration of the opioid dose and active management of side-effects in long-term follow-up studies need to measure both pain relief and quality of life.     

Concerns About Pain and Prescribed Opioids in Taiwanese Oncology Outpatients

Pharmacologic agents are considered to be a cornerstone of cancer pain management. Patients' concerns about use of analgesics are likely to lead to poor pain management. The purpose of this study was to describe participants' responses to their beliefs regarding pain and prescribed opioids. Ninety-two outpatients age ≥18 years who had taken prescribed opioid analgesics for cancer-related pain in two teaching hospitals in the Taipei area completed the Pain Opioid Analgesics Beliefs Scale–Cancer. An important finding of this study is that large numbers of patients had misconceptions about using opioids for pain. Between 33.7% and 68.5% of the patients in this study held negative beliefs about opioids and beliefs about pain. Specifically, 68.5% of the patients agreed that “opioid medication is not good for a person's body.” Many patients (62%) agreed that “the more opioid medicine a patient used, the greater the possibility that he/she might rely on the medicine forever,” and 61.0% agreed that “if a patient starts to use opioid medicine at too early a stage, the medicine will have less of an effect later.” Two-thirds (66.3%) of the sample agreed that adult patients should not use opioid medicine frequently. The findings provide empirical support for the need for better programmatic efforts to improve beliefs of pain and analgesics in Taiwanese oncology outpatients.     

Opioids in Headache

Opioid analgesics have long been used to treat head pain of various types. This has been increasing to a significant degree over the past 25 years because of a trend for more liberal use of opioids in non‐malignant pain. Opioid treatment for acute headache, as well as prophylactically for refractory chronic headache, is controversial. There are a number of adverse effects associated with acute and chronic opioid treatment. Tolerance, dependence, and addiction are prominent issues. This article attempts to analyze the benefits and disadvantages for opioids in the management of migraine and other headache disorders, relying on known properties of this class of medication as well as clinical data. It will mainly focus on 2 topics: the use of opioid medication for the acute treatment of migraine attacks and continuous prophylactic use for refractory chronic migraine.     

Clinical and Demographic Predictors of Interdisciplinary Chronic Pain Rehabilitation Program Treatment Response

Patients treated in interdisciplinary chronic pain rehabilitation programs show long-term improvements in symptoms; however, outcomes may vary across heterogenous patient subpopulations. This longitudinal retrospective study characterizes the influence of opioids, mood, patient characteristics, and baseline symptoms on pain and functional impairment (FI) in 1,681 patients 6-months to 12-months post-treatment in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Linear mixed models showed immediate and durable treatment benefits with nonuniform worsening at follow up which slowed over time. Latent class growth analysis identified three post-treatment trajectories of pain and FI: mild symptoms and durable benefits, moderate symptoms and durable benefits, and intractable symptoms. A fourth pain trajectory showed immediate post-treatment improvement and worsening at follow up. Whether a patient was weaned from opioids was not predictive of treatment trajectory. Racial ethnic minority status, higher levels of post-treatment depression, and lower perceived treatment response were associated with less resolution (moderate symptoms) or intractable symptoms. Not having a college education was predictive of intractable or worsening pain and a moderate course of FI. Older age and male gender was associated with intractable FI. Treatment outcomes may be improved by the development of targeted interventions for patients at risk of poor recovery and/or deteriorating long-term course.PerspectiveThis study examined predictors of treatment response in 1,681 patients treated in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Opioid weaning did not predict outcome. Higher levels of symptoms, lower levels of education, and being a racial-ethnic minority were associated with a less salubrious long-term treatment response.     

A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy

BACKGROUND: Opioid analgesics are the cornerstone of management for malignant pain. Their use in managing chronic, nonmalignant pain, albeit controversial, has increased in recent years. The decisions about whether to initiate opioid therapy or continue it over time should be guided by a comprehensive patient assessment. During long-term treatment, this assessment should focus on a broad range of outcomes, each of which should be documented in the medical record. OBJECTIVE: The goal of this study was to develop an instrument, the Pain Assessment and Documentation Tool (PADT), to focus on key outcomes and provide a consistent way to document progress in pain management therapy over time. METHODS: Items that assess 4 domains (pain relief, patient functioning, adverse events, and drug-related behaviors) were generated with input from a MEDLINE literature search and experts in pain and addiction management. The original tool was field tested by clinicians who applied it to the assessment of patients receiving long-term opioid therapy for the management of chronic, nonmalignant pain. Data analysis and debriefing telephone interviews with a formalized set of questions were then used to rephrase, delete, and refine items to create the final tool. RESULTS: A 6-member expert panel contributed to the initial development of the PADT. Twenty-seven clinicians completed the preliminary version of PADT for 388 patients. The original 59-item tool was modified to create a 41-item tool. The revised PADT was formatted for use as a chart note designed to assist clinicians in assessing and documenting 4 main outcome domains during long-term opioid use. CONCLUSIONS: In this study, the PADT appeared to be a useful tool for clinicians to guide the evaluation of several important outcomes during opioid therapy and provide a simple means of documenting patient care.