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Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use., Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique., Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Background: Intrathecal drug delivery (IDD) and spinal cord stimulator (SCS) systems are implantable devices for the management of both chronic and cancer pain. Although these therapies have favorable long-term outcomes, they are associated with occasional complications including infection. The incidence of infectious complications varies from 2 - 8% and frequently requires prolonged antibiotics and device revision or removal. Cancer patients are particularly susceptible to infectious complications because they are immunocompromised, malnourished, and receiving cytotoxic cancer-related therapies., Objective: Determine if cancer pain patients have a higher incidence of infectious complications following implantation of IDD or SCS systems than non-cancer pain patients., Study Design: Retrospective chart review., Setting: Single tertiary comprehensive cancer hospital., Methods: Following local Institutional Review Board (IRB) approval, we collected data on infectious complications for IDD and SCS systems implanted at MD Anderson Cancer Center for the treatment of cancer and chronic pain. The examined implants were performed from July 15, 2006, to July 14, 2009. In addition, we obtained data regarding patient comorbidities and perioperative risk factors to assess their impact on infectious complications., Results: One hundred forty-two devices were implanted in 131 patients during the examined period. Eighty-three of the devices were IDD systems and 59 were SCS systems. Eighty percent of the patients had a diagnosis of cancer. Four infectious complications were noted with an overall infectious risk of 2.8%. The infection rate was 2.4% for IDD systems versus 3.4% for SCS systems (P = 1). All infections were at the implantable pulse generator (IPG) or pump pocket site. The rate of infection was 2.7% for cancer patients and 3.3% for non-cancer patients (P = 1). Neither the perioperative administration of prophylactic antibiotics (P = 0.4) nor the National Nosocomial Infection Surveillance (NNIS) risk level for individual patients (P = 0.15) were statistically associated with infectious complication. The mean surgical time was longer for cases with infection at 215 ± 93 minutes versus 132 ± 52 minutes for those without infection which was statistically significant (P = 0.02)., Limitations: The major limitation of this study is that it was a retrospective analysis. An additional limitation is that 51(38.9%) of our patients either died or were lost to follow-up during the year following implantation which may have led to an underestimation of our infection rates., Conclusions: The experience of this tertiary cancer pain center demonstrates that infectious complications following implantation of IDD and SCS systems are relatively rare events in cancer patients. Contrary to our initial hypothesis, no difference was found in the infection rate between cancer and non-cancer patients. The main factor associated with increased risk of infectious complications was increased surgical time, indicating a need to minimize patient time in the operating room. The low infectious complication rate seen in this series compared to previous reports in non-cancer patients is likely multifactorial in nature.

Unlabelled: Although many cancer patients who have pain are smokers, the extent of their symptom burden and risk for opioid misuse are not well understood. In this study we analyzed records of patients being treated for cancer pain, 94 of whom were smokers and 392 of whom were nonsmokers, to determine smoking status group differences. Smokers had significantly higher pain intensity, fatigue, depression, and anxiety than nonsmokers (independent samples t-tests P < .002). Smokers were at higher risk for opioid misuse based on the short form of the Screener and Opioid Assessment for Patients with Pain (SOAPP). Specifically, smokers had more frequent problems with mood swings, taking medications other than how they are prescribed, a history of illegal drug use, and a history of legal problems (chi-square tests P ≤ .002). Changes in pain and opioid use were examined in a subset of patients (146 nonsmokers and 46 smokers) who were receiving opioid therapy on at least 2 of the 3 data time points (consult, follow-up 1 month after consult, follow-up 6 to 9 months after consult). Results based on multilevel linear modeling showed that over a period of approximately 6 months, smokers continued to report significantly higher pain than nonsmokers. Both smokers and nonsmokers reported a significant decline in pain across the 6-month period; the rate of decline did not differ across smokers and nonsmokers. No significant difference over time was found in opioid use between smokers and nonsmokers. These findings will guide subsequent studies and inform clinical practice, particularly the relevancy of smoking cessation., Perspective: This article describes pain, symptom burden, and risk for opioid misuse among cancer patients with pain across smoking status. Smoking appears to be a potential mechanism for having an increased pain and symptom burden and risk for opioid misuse. This improved understanding of cancer pain will inform clinical practice., (Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician's armamentarium. Though opioids are used regularly for cancer pain, there is a paucity of literature proving efficacy for long-term use. Cancer is no longer considered a "terminal disease"; 50% to 65% of patients survive for at least 2 years, and there are about 12 million cancer survivors in the United States. There is a concern about side effects, tolerance, abuse and addiction with long-term opioid use and a need to evaluate the effectiveness of opioids for cancer pain., Objective: The objective of this systematic review was to look at the effectiveness of opioids for cancer pain., Study Design: A systematic review of randomized trials of opioids for cancer pain., Methods: A comprehensive review of the current literature for randomized controlled trials (RCTs) of opioids for cancer pain was done. The literature search was done using PubMed, EMBASE, Cochrane library, clinical trials, national clearing house, Web of Science, previous narrative systematic reviews, and cross references. The studies were assessed using the modified Cochrane and Jadad criteria. Analysis of evidence was done utilizing the modified quality of evidence developed by United States Preventive Services Task Force (USPSTF)., Outcome Measures: Pain relief was the primary outcome measure. Secondary outcome measures are quality of life (QoL) and side effects including tolerance and addiction., Results: The level of evidence for pain relief based on the USPSTF criteria was fair for transdermal fentanyl and poor for morphine, tramadol, oxycodone, methadone, and codeine., Limitations: Randomized trials in a cancer setting are difficult to perform and justify. There is a paucity of long-term trials and this review included a follow-up period of only 4 weeks., Conclusion: This systematic review of RCTs of opioids for cancer pain showed fair evidence for the efficacy of transdermal fentanyl and poor evidence for morphine, tramadol, oxycodone, methadone, and codeine.

Unlabelled: Patients with painful vertebral compression fractures produced by multiple myeloma (MM) often experience reduction in pain after spinal augmentation with kyphoplasty or vertebroplasty. Previous studies have shown pain reduction and improvement in functional status after augmentation, but no studies have examined the effect of augmentation on other cancer-related symptoms. We hypothesized that reduction in pain severity would be significantly associated with improvement in other reported symptoms. We retrospectively studied 79 patients who rated pain and symptom severity both before and after kyphoplasty or vertebroplasty. Pain was significantly reduced after spinal augmentation (1.3 on a 0 to 10 scale; effect size [ES] = .59; P < .001), as were anxiety (1.3; ES = .47), drowsiness (1.3; ES = .39), fatigue (1.1; ES = .32), depression (.7; ES = .28), and difficulty thinking clearly (.7; ES = .26) (all P < .05). Greater reduction in pain was associated with a greater number of symptoms being reduced. Interestingly, insomnia worsened regardless of any amount of improvement in pain. Because appropriate symptom control contributes to the overall well-being of cancer patients, future studies of pain reduction procedures should include measures of other symptoms to fully characterize the potential benefit of treating pain., Perspective: Appropriate symptom control contributes to overall well-being for cancer patients. This study demonstrated that pain reduction after spinal augmentation with vertebroplasty or kyphoplasty was positively associated with reduction in other patient-reported cancer-related symptoms. Future studies of these augmentation procedures should measure multiple symptoms, in addition to pain and functional status., (Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background:   Painful vertebral compression fractures (VCFs), whether pathologic or osteoporotic, are a source of morbidity in cancer patients. At our tertiary cancer center, over the past decade we have used vertebroplasty (VP) and kyphoplasty (KP) to treat painful VCFs. More data are needed on the treatment of VCFs in cancer patients with these techniques., Methods:   We retrospectively reviewed the medical records of cancer patients with painful VCFs that had been treated at our institution between January 1, 2001 and May 31, 2008. Information was collected on demographic and clinical characteristics, features of the fractures, procedural details, and complications. Pre- and post-procedural pain and related symptoms were assessed using a subset of patients who had responded to the Brief Pain Inventory and the Edmonton Symptom Assessment Scale., Results:   A total of 407 cancer patients had 1,156 fractures that had been treated with VP or KP during 536 surgical procedures. Patients had an average of 2.8 fractures (range, 1-10). The majority of patients had pathologic fractures due to multiple myeloma (43%) or osteoporotic fractures (35%). Most fractures occurred in the thoracolumbar region. Adjacent-level fractures occurred in 18% of patients. Surgery provided significant relief from pain and several related symptoms. Symptomatic, serious complications requiring open surgery occurred in two cases (<0.01%) in our series., Conclusions:   Our single-center experience revealed that a large number of cancer patients suffer from painful VCFs. The use of VP or KP in treating painful VCFs in cancer patients has good efficacy and an acceptably low complication rate., (Wiley Periodicals, Inc.)

Background: The growing awareness of opioid abuse and addiction in the chronic pain population, along with increasing cancer survivorship, has heightened our awareness of this potential problem in the cancer patient. An increasing number of patients who abuse opioids have been identified in our clinical setting., Objective: We present an algorithm of multidisciplinary care for the treatment of cancer patients at risk for abusing opioids., Setting: Two illustrative patient examples were identified recently from our clinic., Results: These 2 patient examples demonstrate our multidisciplinary approach to treatment. A discussion of safe prescribing principles adapted from the literature is presented. Also, a brief point of added complexity is introduced; specifically, ethical considerations due to the unique nature of cancer pain., Limitations: Although validation studies exist for the use of screening tools in patients with chronic noncancer pain, there have been no instrument validation studies on patients with cancer pain. The educational treatment model that we refer to regarding facilitating safe use of opioids also has not been studied on patients with cancer pain. Lastly, we express caution in generalizing our guidelines to patients with noncancer pain. Our patient population differs in the multiple co-existing stressors and symptom burden associated with cancer., Conclusions: We have become increasingly aware of the problem of opioid abuse in the cancer pain population. With an approach to using safe prescribing principles adapted from chronic pain literature, and an ethically based multidisciplinary approach, clinicians can continue to treat pain successfully in the opioid-misusing cancer patient. We outline our approach in this article.

Background: Use of opioids for chronic non-cancer pain (CNCP) has increased in recent years because this pain had been undertreated. There was also a simultaneous increase in misuse and abuse of opioids. Deaths due to such abuse and misuse also have risen as seen in the many reports published every day in local papers as well as in the medical literature. So, it is imperative that patients who are prescribed these medications be monitored for adherence so misuse and abuse can be curtailed and opioids are available to those who genuinely need them for chronic pain control. There are various screening tools available to monitor such adherence, and there is an abundance of literature about it in addiction and psychiatric medicine. There is, though, a paucity of such literature as applied to pain medicine., Objectives: Our objectives for this review were twofold. We wanted to identify which screening tools are available to monitor opioid adherence and we wanted to see if there were prospective comparative studies of these tools to identify a single best tool that can be applied to all chronic non-cancer pain patients managed with opioids., Study Design: We did a review of the current literature about monitoring of opioid adherence. We also looked at their use, validity, and comparative studies., Methods: We performed a literature search using PubMed, EMBASE, and the Cochrane library. The search was conducted using the terms opioids, non-cancer pain, monitoring, and adherence. The databases from 1996 to November 2010 were reviewed. The search included prospective and retrospective studies, review articles, and FDA records. Bibliographies and cross references were reviewed when deemed appropriate., Conclusion: We found 52 publications, of which 22 met the criteria to be included in this manuscript. We found only one study that was prospective, and compared the various screening tools that are available to monitor opioid adherence. In the majority of the studies the number treated was small. There was not a single screening tool that can be applied universally to all patients who are on opioid therapy for chronic non-cancer pain.

Background: The prevalence of cancer-related pain and residual pain in cancer survivors is high. Opioids serve as the gold standard for treating moderate to severe cancer pain. The evaluation of the effectiveness of opioids in chronic non-cancer pain has shown a lack of effectiveness, or rather weak evidence for some of the drugs. In contrast, in cancer pain, opioids are expected to be very effective. Due to the nature of the disease, there is evidence of a paucity of randomized trials investigating opioid effectiveness in cancer pain on a long-term basis. Consequently, the effectiveness of opioids in managing cancer-related pain warrants further evidence-based review beyond randomized trials, including observational studies and case reports., Methods: The comprehensive literature search was conducted for the period 1996 through June 2010. Databases for the search included PubMed, EMBASE, Cochrane Reviews, and clinicaltrials.gov, along with reviews and cross references. Methodologic quality assessment of the observational studies managing chronic cancer pain with opioids was conducted utilizing the Agency for Healthcare Research and Quality (AHRQ) criteria for observational studies. Analysis of evidence included 5 levels of evidence developed by the United States Preventive Services Task Force (USPSTF) ranging from Level I to III with 3 subcategories in Level II. Grading recommendations were based on Guyatt et al's recommendations with 6 levels: 3 in the strong category and 3 in the weak category., Results: This evaluation is of 18 manuscripts considered for inclusion; 7 manuscripts met the inclusion criteria based on AHRQ quality assessment. Level of evidence for opioid therapy in cancer pain was Level II-3, and recommendations were 1C/strong recommendation based on observational studies, which could change based on future evidence., Conclusion: This systematic review of observational studies indicates Level II-3 evidence for effectiveness of opioids in cancer pain therapy, with 1C/strong recommendation based on observational studies, which could change based on future evidence.

Background: 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 tolerance, dependance, or abuse. While the debate continues, the use of chronic opioid therapy for chronic non-cancer pain has increased exponentially. Even though evidence is limited, multiple expert panels have concluded that chronic opioid therapy can be effective therapy for carefully selected and monitored patients with chronic non-cancer pain., Study Design: A systematic review of randomized trials of opioid management for chronic non-cancer pain., Objective: The objective of this systematic review is to evaluate the clinical efficacy of opioids in the treatment of chronic non-cancer pain., Methods: A comprehensive evaluation of the literature relating to opioids in chronic non-cancer pain was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs) and Jadad criteria. A literature search was conducted by using PubMed, EMBASE, Cochrane library, ECRI Institute Library, U.S. Food and Drug Administration (FDA) website, U.S. National Guideline Clearinghouse (NGC), Database of Abstracts of Reviews of Effectiveness (DARE), clinical trials, systematic reviews and cross references from systematic reviews. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) and used by other systematic reviews and guidelines., Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, withdrawals, and adverse effects., Results: Based on the USPSTF criteria, the indicated level of evidence was fair for Tramadol in managing osteoarthritis. For all the drugs assessed, including Tramadol, for all other conditions, the evidence was poor based on either weak positive evidence, indeterminate evidence, or negative evidence., Limitations: A paucity of literature, specifically with follow-up beyond 12 weeks for all types of opioids with controlled trials for various chronic non-cancer pain conditions., Conclusions: This systematic review illustrated fair evidence for Tramadol in managing osteoarthritis with poor evidence for all other drugs and conditions. Thus, recommendations must be based on non-randomized studies.

Pain continues to be a significant symptom burden in cancer patients, with prevalence in 53% of patients at all stages of cancer and as high as 58% to 69% in those with advanced cancer. Neurolytic blocks are a mainstay in the armamentarium of cancer pain management, more so in intractable pain from advanced cancer. There is no clear consensus on patient selection, technique, or timing of these blocks. Here we discuss the use of various neurolytic blocks for cancer pain and detail some of the recent literature and our experience.