A systematic review of the evidence for the efficacy of opioids for chronic non-cancer pain in community-dwelling older adults

We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans. Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared. From 1997 to 2005, age-gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%-9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women. Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings.

Long-term effects of opioids on the cardiovascular system

Over the past decade, long-term use of prescription opioids for chronic non-cancer pain has risen globally despite the associated risks. Most opioid users receive their first prescription in primary care. To investigate the perspective of patients who are long-term opioid users in primary care regarding the role of healthcare providers (HCPs) in their prolonged opioid use. Semi-structured interviews in Dutch primary care. We recruited patients who were long-term users of opioids for chronic non-cancer pain from seven community pharmacies in the Netherlands. In-depth, semi-structured interviews focused on patients' experiences with long-term opioid use, access to opioids, and the guidance of their HCPs (primarily their GPs and pharmacists). A directed content analysis was conducted on the transcribed interviews using NVivo. Participants (n = 25) described ways in which HCPs impacted their long-term use of opioids. These encompassed the initiation of treatment, chronic use of opioids, and discontinuation of treatment. Participants stressed the need for risk counselling during initial prescribing, ongoing medication evaluations including tapering conversations, and more support from their HCP during a tapering attempt. Patients' perspectives illustrate the important role of HCPs across the spectrum of opioid use - from initiation to tapering. The results of this study underscore the importance of clear risk counselling starting at initial prescribing, repeated medication assessments throughout treatment, addressing tapering at regular intervals, and strong support during tapering. These insights carry significant implications for clinical practice, emphasising the importance of informed and patient-centred care when it comes to opioid use for chronic non-cancer pain management.

Opioids are associated with higher risk for ataxic breathing and sleep apnea. We conducted a systematic literature review and meta-analysis to assess the influence of long-term opioid use on the apnea-hypopnea and central apnea indices (AHI and CAI, respectively). A systematic review protocol (Cochrane Handbook guidelines) was developed for the search and analysis. We searched Embase, Medline, ACP Journal Club, and Cochrane Database up to November 2014 for three topics: (1) narcotics, (2) sleep apnea, and (3) apnea-hypopnea index. The outcome of interest was the variation in AHI and CAI in opioid users versus non-users. Two reviewers performed the data search and extraction, and disagreements were resolved by discussion. Results were combined by standardized mean difference using a random effect model, and heterogeneity was tested by χ(2) and presented as I(2) statistics. Seven studies met the inclusion criteria, for a total of 803 patients with obstructive sleep apnea (OSA). We compared 2 outcomes: AHI (320 opioid users and 483 non-users) and 790 patients with CAI (315 opioid users and 475 non-users). The absolute effect size for opioid use was a small increased in apnea measured by AHI = 0.25 (95% CI: 0.02-0.49) and a medium for CAI = 0.45 (95% CI: 0.27-0.63). Effect consistency across studies was calculated, showing moderate heterogeneity at I(2) = 59% and 29% for AHI and CAI, respectively. The meta-analysis results suggest that long-term opioid use in OSA patients has a medium effect on central sleep apnea.

Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'. To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults. We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework. We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity. A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.

The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Osteoarthritis is the most common degenerative disease in humans. It usually begins in middle age and is progressive. Chronic pain in older people presents a significant obstacle in maintaining function and independence. Previous studies have shown that music can improve motivation, elevate mood, and increase feelings of control in older people. The purpose of this randomized clinical trial was to examine the influence of music as a nursing intervention on osteoarthritis pain in elders. Data were collected using the short form of the McGill Pain Questionnaire with 66 elders suffering from chronic osteoarthritis pain. Differences in perceptions of pain were measured over 14 days in an experimental group who listened to music for 20 minutes daily and a control group who sat quietly for 20 minutes daily. All participants completed the Short Form McGill Pain Questionnaire (SF-MPQ) on day 1, 7, and 14 of the study. Results of t-tests indicated that those who listened to music had less pain on both the Pain Rating Index on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001) and on the Visual Analogue Scale on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001), when compared with those who sat quietly and did not listen to music. A repeated measure analysis of variance controlling for pretest measures demonstrated a significant decrease in pain among experimental group participants when compared with the control group on the pain descriptor section of the SF-MPQ (P = 0.001) and the visual analogue portion of the SF-MPQ (P = 0.001). Listening to music was an effective nursing intervention for the reduction of chronic osteoarthritis pain in the community-dwelling elders in this study.

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.

Preoperative opioid use: a modifiable risk factor for poor postoperative outcomes

BackgrOunD: The use of opioids for chronic noncancer pain increased 222% from 1992 to 2002. Opioid dependence has also increased significantly, leading to a burden on patients, employers, insurers, society, and the entire health care system. It is imperative that opioid dependence is addressed and treated properly, in order to return patients to being productive participants in the workplace and society. OBjecTIve: To provide an overview of addiction, abuse, and dependence and identify risk factors for addiction. Summary: Studies have shown that intensive use of opioids is associated with increased utilization of costly health care services, prolonged disability, and continued use of opioids, leading to abuse and dependence in many patients. While identifying patients at risk for developing opioid dependence is difficult, there are many risk stratification tools now available to practitioners, including the Opioid risk Tool (OrT) or Screener and Opioid assessment for Patients with Pain (SOaPP). understanding the differences between dependence, addiction, and tolerance is essential to managing patients on opioids. cOncLuSIOn: It is imperative that patients be properly managed when being treated for pain. Physicians and employers have to be able to identify patients at risk for opioid abuse or exhibiting symptoms of opioid abuse and know how to address their needs. J Manag Care Pharm. 2010;16(1-b):S4-S8 copyright © 2010, academy of managed care Pharmacy. all rights reserved. SAIRA A. JAN, MS, PharmD, is Clinical Director, Blue Cross Blue Shield of New Jersey, and Associate Professor at the Ernest Mario School of Pharmacy of Rutgers, the State University of New Jersey. AUTHOR CORRESPONDENCE: Saira A. Jan, MS, PharmD, Director of Clinical Pharmacy Management, Horizon Blue Cross Blue Shield of New Jersey, Newark, NJ 07105-2200. Tel.: 973.466.6192; Fax: 973.466.4665. E-mail: Saira_ Jan@horizon-bcbsnj.com. Author Drug abuse and dependence are on the rise. The widespread use of opioid analgesics for the treatment of chronic noncancer pain and for acute pain management began in the late 1980s. Between 1980 and 2000, there was an increase from 8% to 16% in the number of patients receiving opioids for chronic musculoskeletal pain and an increase in use from 8% to 11% for acute musculoskeletal pain.1,2 In 2002, reports show a 222% increase in the absolute number or prescriptions for opioid narcotics over the previous 10-year period.1,3 Today, the most common method for treating chronic pain is with the use of prescription analgesics, including opioids.4 In the 1970s, chronic pain patients were encouraged by society to avoid opioids due to concerns that taking opioids invariably led to addiction.5 In the early 1980s, the pendulum shifted to widespread use of opioids, based on results of a small study (n = 20) showing chronic pain patients could benefit from pain control using opioids with little risk of developing dependence.6,7,8,9 Additionally, in the 1990s, a review article of several studies showed patients with neuropathic pain experienced relief from opioids.6,8,9 Unfortunately, many patients continue to take opioids despite inadequate pain control. Patients on chronic narcotic pain medications generate higher costs of health care, have higher surgery rates, a greater level of disability, and higher rates of late opioid use.10 Late opioid use is defined as receiving ≥ 5 opioid prescriptions between 30 and 730 days after onset of pain, a quantity of prescriptions that is generally beyond what is considered appropriate use for symptom control for an acute pain exacerbation.1 In a retrospective cohort study of 8,443 workers’ compensation claims for acute disabling lower back pain, looking at claims from January 1, 2002, and December 31, 2003, intensive use of opioids early in treatment was associated with worse long-term outcomes, increased use of costly medical services (including surgery), prolonged disability, and continued use of opioids.1 One dilemma that arises with using opioids long term is that hyperalgesia (increased pain sensitivity), decreased libido and other hormonal effects, and depression may occur, as well as tolerance. Statistics have shown that at least 1 of these effects is experienced by 51% of all patients taking oral opioids.2 Another concern is the risk of dependence and addiction. For most of the twentieth century, opioid dependence has been problematic.11 A review of 24 studies (2,507 chronic pain patients) have shown that there is a 3.3% risk of developing addiction.6 While this percentage is low, it represents a large population that is hard to manage. Evaluating and re-evaluating patients who are at higher risk of developing addiction is something that all clinicians treating chronic pain patients treated with opioids should be performing on an ongoing basis.6

While opioids are effective in carefully selected patients with chronic non-cancer pain (CNCP), they are associated with potential risks. Therefore, treatment recommendations for the safe and effective use of opioids in this patient population are needed. A multidisciplinary expert panel was convened by the Pain Association of Singapore to develop practical evidence-based recommendations on the use of opioids in the management of CNCP in the local population. This article discusses specific recommendations for various common CNCP conditions. Available data demonstrate weak evidence for the long-term use of opioids. There is moderate evidence for the short-term benefit of opioids in certain CNCP conditions. Patients should be carefully screened and assessed prior to starting opioids. An opioid treatment agreement must be established, and urine drug testing may form part of this agreement. A trial duration of up to 2 months is necessary to determine efficacy, not only in terms of pain relief, but also to document improvement in function and quality of life. Regular reviews are essential with appropriate dose adjustments, if necessary, and routine assessment of analgesic efficacy, aberrant behaviour and adverse effects. The reasons for discontinuation of opioid therapy include side effects, lack of efficacy and aberrant drug behaviour. Due to insufficient evidence, the task force does not recommend the use of opioids as first-line treatment for various CNCP. They can be used as secondor third-line treatment, preferably as part of a multimodal approach. Additional studies conducted over extended periods are required.

Should placebo be used routinely for chronic pain in older people?

human rights. 2– 4 Noticeable shifts in attitude have occurred in recent years regarding the use of opioids for the treatment of benign and malignancy-related pain. Primary care physicians and pain specialists prescribe opioids to a greater number of patients and in doses appropriate to needs. 3–7 A variety of opioid analgesics and delivery systems have been introduced that have increased patient satisfaction, physician acceptance, and overall use. Concomitant with improvements in pain relief and quality of life, an increasing number of patients are affected by issues related to opioid tolerance and physical dependence. There have been only a small number of published reviews that address the treatment of acute pain in patients with substance abuse disorders, 3–5 and fewer have focused specifically on perioperative pain management in opioid-dependent patients. 6,7 This review outlines factors responsible for opioid tolerance, physical dependence, and addiction and provides perioperative analgesic dosing guidelines for this specialized subset of patients. Many patients who present for surgery and anesthesia may be opioid dependent or at least moderately tolerant to the therapeutic effects of opioid analgesics. 5–7 Causal factors underlying dependency include substance use disorder and, more commonly, legitimate use of opioid analgesics for treatment of chronic benign pain or malignancy-associated pain. Perioperative management of opioid-dependent patients poses a special challenge to primary caregivers, anesthesiologists, and pain specialists alike. This problem emanates from the often-conflicting needs to balance the rights of the patient on one hand and concerns of safety, diversion, and abuse on the

PurposeDenmark has a high consumption of prescribed opioids, and many citizens with chronic non-cancer pain (CNCP). Therefore, we aimed to characterize and assess epidemiological risk factors associated with long-term non-cancer opioid use among Danish citizens.Patients and MethodsWe conducted a longitudinal, retrospective, observational, register-based study using nationwide databases containing essential medical, healthcare, and socio-economic information. Statistical analysis, including backward stepwise logistic regression analysis, was used to explain long-term opioid use by individuals filling at least one prescription for an opioid product N02AA01–N02AX06 during 01/01/2004–31/12/2017, follow-up until the end of 2018.ResultsThe analyzed cohort contained N=1,683,713 non-cancer opioid users, of which 979,666 were classified with CNCP diagnosis using ICD-10 codes. Long-term opioid use was predicted by a mean of 1,583.30 and a median of 300 oral morphine equivalent mg (OMEQ) per day during the first year, together with divorced, age group 40–53 years, retirement, receiving social welfare or unemployment ≥6 months. In addition, living in Northern Jutland, co-medications such as beta-blockers, anti-diabetics, anti-rheumatics, and minor surgery ≤90 days before inclusion. Protective variables were an education level of secondary school or higher, children living at home, household income of middle or highest tertile, opioid doses in either the 2nd or 3rd quartile OMEQ, male, the oldest age group, living in the Capital Region or Zealand, co-medication lipid-lowering, one comorbidity, heart failure, surgeries ≤90 days before the index: lips/teeth/jaw/mouth/throat, heart/vessels, elbow/forearm, hip/thigh, knee/lower leg/ankle/foot.ConclusionLong-term opioid users differ epidemiologically from those using opioids for a shorter period. The study findings are essential for future recommendations revision in Denmark and comparable countries.

BACKGROUND: Long-term opioid therapy was prescribed with increasing frequency over the past decade. However, factors surrounding long-term use of opioids in older adults remains poorly understood, probably because older people are not at the center stage of the national opioid crisis. OBJECTIVES: To estimate the annual utilization and trends in long-term opioid use among older adults in the United States. STUDY DESIGN: Retrospective cohort study. SETTING: Data from Medicare-enrolled older adults. METHODS: This study utilized a nationally representative sample of Medicare administrative claims data from the years 2012 to 2016 containing records of health care services for more than 2.3 million Medicare beneficiaries each year. Medicare beneficiaries who were 65 years of age or older and who were enrolled in Medicare Parts A, B, and D, but not Part C, for at least 10 months in a year were included in the study. We measured annual utilization and trends in new long-term opioid use episodes over 4 years (2013–2016). We examined claims records for the demographic characteristics of the eligible individuals and for the presence of chronic non-cancer pain (CNCP), cancer, and other comorbidities. RESULTS: From 2013 to 2016, administrative claims of approximately 2.3 million elderly Medicare beneficiaries were analyzed in each year with a majority of them being women (~56%) and white (~82%) with a mean age of approximately 75 years. The proportion of all eligible beneficiaries with at least one new opioid prescription increased from 6.64% in 2013, peaked at 10.32% in 2015, and then decreased to 8.14% in 2016. The proportion of individuals with long-term opioid use among those with a new opioid prescription was 12.40% in 2013 and 10.20% in 2016. Among new long-term opioid users, the proportion of beneficiaries with a cancer diagnosis during the study years increased from 13.30% in 2013 to 15.67% in 2016, and the proportion with CNCP decreased from 30.25% in 2013 to 27.36% in 2016. Across all years, long-term opioid use was consistently high in the Southern states followed by the Midwest region. LIMITATIONS: This study used Medicare fee-for-service administrative claims data to capture prescription fill patterns, which do not allow for the capture of individuals enrolled in Medicare Advantage plans, cash prescriptions, or for the evaluation of appropriateness of prescribing, or the actual use of medication. This study only examined long-term use episodes among patients who were defined as opioid-naive. Finally, estimates captured for 2016 could only utilize data from 9 months of the year to capture 90-day long-term-use episodes. CONCLUSIONS: Using a national sample of elderly Medicare beneficiaries, we observed that from 2013 to 2016 the use of new prescription opioids increased from 2013 to 2014 and peaked in 2015. The use of new long-term prescription opioids peaked in 2014 and started to decrease from 2015 and 2016. Future research needs to evaluate the impact of the changes in new and long-term prescription opioid use on population health outcomes. KEY WORDS: Long-term, opioids, older adults, trends, Medicare, chronic non-cancer pain, cancer, cohort study