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Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Author/s: 
McDonagh, M. S., Wagner, J., Ahmed, A. Y., Morasco, B., Kansagara, D., Chou, R.

Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain.

Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021.

Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects.

Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported.

Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

Mobile Telemedicine for Buprenorphine Treatment in Rural Populations With Opioid Use Disorder

Author/s: 
Weintraub, E., Seneviratne, C., Anane, J.

Importance
The demand for medications for opioid use disorder (MOUD) in rural US counties far outweighs their availability. Novel approaches to extend treatment capacity include telemedicine (TM) and mobile treatment on demand; however, their combined use has not been reported or evaluated.

Objective
To evaluate the use of a TM mobile treatment unit (TM-MTU) to improve access to MOUD for individuals living in an underserved rural area.

Design, Setting, and Participants
This quality improvement study evaluated data collected from adult outpatients with a diagnosis of OUD enrolled in the TM-MTU initiative from February 2019 (program inception) to June 2020. Program staff traveled to rural areas in a modified recreational vehicle equipped with medical, videoconferencing, and data collection devices. Patients were virtually connected with physicians based more than 70 miles (112 km) away. Data analysis was performed from June to October 2020.

Intervention
Patients received buprenorphine prescriptions after initial teleconsultation and follow-up visits from a study physician specialized in addiction psychiatry and medicine.

Main Outcomes and Measures
The primary outcome was 3-month treatment retention, and the secondary outcome was opioid-positive urine screens. Exploratory outcomes included use of other drugs and patients’ travel distance to treatment.

Results
A total of 118 patients were enrolled in treatment, of whom 94 were seen for follow-up treatment predominantly (at least 2 of 3 visits [>50%]) on the TM-MTU; only those 94 patients’ data are considered in all analyses. The mean (SD) age of patients was 36.53 (9.78) years, 59 (62.77%) were men, 71 (75.53%) identified as White, and 90 (95.74%) were of non-Hispanic ethnicity. Fifty-five patients (58.51%) were retained in treatment by 3 months (90 days) after baseline. Opioid use was reduced by 32.84% at 3 months, compared with baseline, and was negatively associated with treatment duration (F = 12.69; P = .001). In addition, compared with the nearest brick-and-mortar treatment location, TM-MTU treatment was a mean of 6.52 miles (range, 0.10-58.70 miles) (10.43 km; range, 0.16-93.92 km) and a mean of 10 minutes (range, 1-49 minutes) closer for patients.

Conclusions and Relevance
These data demonstrate the feasibility of combining TM with mobile treatment, with outcomes (retention and opioid use) similar to those obtained from office-based TM MOUD programs. By implementing a traveling virtual platform, this clinical paradigm not only helps fill the void of rural MOUD practitioners but also facilitates access to underserved populations who are less likely to reach traditional medical settings, with critical relevance in the context of the COVID-19 pandemic.

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

Author/s: 
W. A., Chung, C. P., Murray, K. T., Malow, B. A., Daugherty, J. R., Stein, C. M.

Background: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.

Methods and findings: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.

Conclusions: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

Keywords 
opioids Hypnotics cohort study mortality Drug Overdose

Non-Surgical Interventions for Lumbar Spinal Stenosis Leading To Neurogenic Claudication: A Clinical Practice Guideline

Author/s: 
Bussieres, A., Cancelliere, C., Ammendolia, C., Comer, C. M., Zoubi, F. A., Chatillon, C. E., Chernish, G., Cox, J. M., Gliedt, J. A., Haskett, D., Jensen, R. K., Marchand, A. A., Tomkins-Lane, C., O'Shaughnessy, J., Passmore, S., Schneider, M. J., Shipka, P., Stewart, G., Stuber, K., Yee, A., Ornelas, J.

Lumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is increasingly common with an aging population and can be associated with significant symptoms and functional limitations. We developed this guideline to present the evidence and provide clinical recommendations on nonsurgical management of patients with LSS causing NC. Using the GRADE approach, a multidisciplinary guidelines panel based recommendations on evidence from a systematic review of randomized controlled trials and systematic reviews published through June 2019, or expert consensus. The literature monitored up to October 2020. Clinical outcomes evaluated included pain, disability, quality of life, and walking capacity. The target audience for this guideline includes all clinicians, and the target patient population includes adults with LSS (congenital and/or acquired, lateral recess or central canal, with or without low back pain, with or without spondylolisthesis) causing NC. The guidelines panel developed 6 recommendations based on randomized controlled trials and 5 others based on professional consensus, summarized in 3 overarching recommendations: (Grade: statements are all conditional/weak recommendations) Recommendation 1. For patients with LSS causing NC, clinicians and patients may initially select multimodal care nonpharmacological therapies with education, advice and lifestyle changes, behavioral change techniques in conjunction with home exercise, manual therapy, and/or rehabilitation (moderate-quality evidence), traditional acupuncture on a trial basis (very low-quality evidence), and postoperative rehabilitation (supervised program of exercises and/or educational materials encouraging activity) with cognitive-behavioral therapy 12 weeks postsurgery (low-quality evidence). Recommendation 2. In patients LSS causing NC, clinicians and patients may consider a trial of serotonin-norepinephrine reuptake inhibitors or tricyclic antidepressants. (very low-quality evidence). Recommendation 3. For patients LSS causing NC, we recommend against the use of the following pharmacological therapies: nonsteroidal anti-inflammatory drugs, methylcobalamin, calcitonin, paracetamol, opioids, muscle relaxants, pregabalin (consensus-based), gabapentin (very low-quality), and epidural steroidal injections (high-quality evidence). PERSPECTIVE: This guideline, on the basis of a systematic review of the evidence on the nonsurgical management of lumbar spine stenosis, provides recommendations developed by a multidisciplinary expert panel. Safe and effective non-surgical management of lumbar spine stenosis should be on the basis of a plan of care tailored to the individual and the type of treatment involved, and multimodal care is recommended in most situations.

Keywords 
Lumbar Spinal Stenosis Neurogenic Claudication Clinical symptoms guideline

The opioid crisis: a contextual, social-ecological framework

Author/s: 
Jalali, Mohammad S., Botticelli, Michael, Hwang, Rachael C., Koh, Howard K., McHugh, R. Kathryn

The prevalence of opioid use and misuse has provoked a staggering number of deaths over the past two and a half decades. Much attention has focused on individual risks according to various characteristics and experiences. However, broader social and contextual domains are also essential contributors to the opioid crisis such as interpersonal relationships and the conditions of the community and society that people live in. Despite efforts to tackle the issue, the rates of opioid misuse and non-fatal and fatal overdose remain high. Many call for a broad public health approach, but articulation of what such a strategy could entail has not been fully realised. In order to improve the awareness surrounding opioid misuse, we developed a social-ecological framework that helps conceptualise the multivariable risk factors of opioid misuse and facilitates reviewing them in individual, interpersonal, communal and societal levels. Our framework illustrates the multi-layer complexity of the opioid crisis that more completely captures the crisis as a multidimensional issue requiring a broader and integrated approach to prevention and treatment.

Keywords 
Opioid Use Disorder opioids social-ecological framework RISEOK Opioid Epidemic

Challenges and Approaches to Population Management of Long-Term Opioid Therapy Patients

Author/s: 
Stephens, Kari A., Ike, Brooke, Baldwin, Laura-Mae, Packer, Christine, Parchman, Michael

Purpose: Primary care is challenged with safely prescribing opioids for patients with chronic noncancer pain (CNCP), specifically to address risks for overdose, opioid use disorder, and death. We identify sociotechnical challenges, approaches, and recommendations in primary care to effectively track and monitor patients on long-term opioid therapy, a key component for supporting adoption of opioid prescribing guidelines.

Methods: We examined qualitative data (field notes and postintervention interview and focus group transcripts) from 6 rural and rural-serving primary care organizations with 20 clinic locations enrolled in a study evaluating a practice redesign program to improve opioid medication management for CNCP patients. Two independent researchers used content analysis to categorize data into key themes to develop an understanding of sociotechnical factors critical to creating and implementing an approach to tracking and monitoring of patients on long-term opioid therapy in primary care practices.

Results: Four factors were critical to developing a tracking and monitoring system. For each we describe common challenges and approaches used by the clinics to overcome then. The first factor, buy-in and participation, was essential for accomplishing the other 3. The other factors occurred sequentially: 1) cohort identification-finding the right patients, 2) data collection and extraction-tracking the right data, and 3) data use-monitoring patients and adjusting care processes.

Conclusions: We identified common challenges and approaches to tracking and monitoring patients using long-term opioid therapy for CNCP in primary care. Based on these findings we provide recommendations to build capacity for tracking and monitoring for organizations that are engaged in improving safe opioid-prescribing practices for CNCP in primary care.

Keywords 
Capacity Building Chronic Disease chronic pain Disease Management Drug Overdose 2019-nCOV 1,4-DMAA primary health care RISEOK

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer

Author/s: 
Winn, Aaron N., Check, Devon K., Farkas, Amy, Fergestrom, Nicole M., Neuner, Joan M., Roberts, Andrew W.

Importance: National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population.

Objective: To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment.

Design, setting, and participants: This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020.

Exposures: Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims.

Main outcomes and measures: Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics.

Conclusions and relevance: These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.

Keywords 
RISEOK aged elderly Opioid-Related Disorders opioids pain management

Risk Factors Associated With Transition From Acute to Chronic Low Back Pain in US Patients Seeking Primary Care

Author/s: 
Stevans, Joel M., Delitto, Anthony, Khoja, Samannaaz, Patterson, Charity G., Smith, Clair N., Schneider, Michael J., Freburger, Janet K., Greco, Carol M., Freel, Jennifer A., Sowa, Gwendolyn A., Wasan, Ajay D., Brennan, Gerard P., Hunter, Stephen J., Minick, Kate I., Wegener, Stephen T., Ephraim, Patti L., Friedman, Michael", Jason M., Robert B.

Importance: Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP.

Objective: To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care.

Design, setting, and participants: This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020.

Exposures: SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral).

Main outcomes and measures: Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records.

Results: Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001).

Conclusions and relevance: In this cohort study, the transition rate to chronic LBP was substantial

Keywords 
back pain primary care Low Back Pain opioids LBP SBT

Interventions for Breathlessness in Patients With Advanced Cancer

Author/s: 
Gupta, A., Waldfogel, J.M., Sharma, R., Feliciano, J.L., Sedhom, R., Day, J., Gersten, R.A., Davidson, P.M.

Main Points

For patients with advanced cancer:

  • Airflow interventions (fans) were more effective for improving breathlessness compared with usual care or sham.
  • Bilevel ventilation (a form of noninvasive positive pressure ventilation) was more effective than standard supplemental oxygen for improving breathlessness.
  • Acupressure/reflexology were more effective than usual care or sham for improving breathlessness.
  • Neither behavioral/psychoeducational interventions alone nor activity/rehabilitation interventions alone were more effective than usual care for improving breathlessness. However, multicomponent nonpharmacological interventions that combined these, with integrative medicine interventions, were more effective than usual care for improving breathlessness.
  • Opioids were not more effective than placebo or anxiolytics for improving breathlessness or exercise capacity; most of these studies in advanced cancer were of exertional breathlessness. Studies on opioids showed no differences in effectiveness between different doses or routes of administration for improving breathlessness.
  • Anxiolytics were not more effective than placebo for improving breathlessness.
  • Both nonpharmacological and pharmacological interventions led to adverse event-related dropouts in a small percentage of patients.

Structured Abstract

Objectives. To assess benefits and harms of nonpharmacological and pharmacological interventions for breathlessness in adults with advanced cancer.

Data sources. We searched PubMed®, Embase®, CINAHL®, ISI Web of Science, and the Cochrane Central Register of Controlled Trials through early May 2020.

Review methods. We included randomized controlled trials (RCTs) and observational studies with a comparison group evaluating benefits and/or harms, and cohort studies reporting harms. Two reviewers independently screened search results, serially abstracted data, assessed risk of bias, and graded strength of evidence (SOE) for key outcomes: breathlessness, anxiety, health-related quality of life, and exercise capacity. We performed meta-analyses when possible and calculated standardized mean differences (SMDs).

Results. We included 48 RCTs and 2 retrospective cohort studies (4,029 patients). The most commonly reported cancer types were lung cancer and mesothelioma. The baseline level of breathlessness varied in severity. Several nonpharmacological interventions were effective for breathlessness, including fans (SMD -2.09 [95% confidence interval (CI) -3.81 to -0.37]) (SOE: moderate), bilevel ventilation (estimated slope difference -0.58 [95% CI -0.92 to -0.23]), acupressure/reflexology, and multicomponent nonpharmacological interventions (behavioral/psychoeducational combined with activity/rehabilitation and integrative medicine). For pharmacological interventions, opioids were not more effective than placebo (SOE: moderate) for improving breathlessness (SMD -0.14 [95% CI -0.47 to 0.18]) or exercise capacity (SOE: moderate); most studies were of exertional breathlessness. Different doses or routes of administration of opioids did not differ in effectiveness for breathlessness (SOE: low). Anxiolytics were not more effective than placebo for breathlessness (SOE: low). Evidence for other pharmacological interventions was limited. Opioids, bilevel ventilation, and activity/rehabilitation interventions had some harms compared to usual care.

Conclusions. Some nonpharmacological interventions, including fans, acupressure/reflexology, multicomponent interventions, and bilevel ventilation, were effective for breathlessness in advanced cancer. Evidence did not support opioids or other pharmacological interventions within the limits of the identified studies. More research is needed on when the benefits of opioids may exceed harms for broader, longer term outcomes related to breathlessness in this population.

Prevention, Diagnosis, and Management of Opioids, Opioid Misuse and Opioid Use Disorder in Older Adults

Author/s: 
Agency for Healthcare Research and Quality

Structured Abstract

Background. Opioid-related harms are increasing among older adults. Until we better understand the factors contributing to this trend, we will be unable to design and implement effective interventions to optimally manage opioid use and its potential harms among older adults. Although considerable research has been done in younger or mixed-age populations, the degree to which it is directly applicable to older adults is uncertain.

Objectives. To provide a framework for understanding how to reduce adverse outcomes of opioid use among older adults, and to describe the evidence available for different factors associated with and interventions to reduce adverse outcomes related to opioid use in this population.

Approach. With input from a diverse panel of content experts and other stakeholders, we developed a conceptual framework and evidence map to characterize empirical studies of factors associated with opioid-related outcomes and interventions to reduce opioid-related harms in older adults. We identified relevant literature among older adults (age ≥60 years) for an evidence map by systematically searching PubMed, PsycINFO, and CINAHL for studies published in English between 2000 and May 6, 2020.

Findings. We identified 5,933 citations, from which we identified 41 studies with multivariable models of factors associated with opioid-related outcomes and 16 studies of interventions in older adults. More than half (22/41) of the multivariable analysis studies evaluated factors associated with long-term opioid use (which, though not a harm per se, may increase the risk of harms if not appropriately managed). Prior or early postoperative opioid use, or greater amounts of prescribed opioids (high number of opioid prescriptions or higher opioid dose), were consistently (100% agreement) and strongly (measure of association ≥2.0) associated with long-term opioid use. Back pain, depression, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), and fibromyalgia also had consistent, but weaker, associations with long-term opioid use. Several factors were mostly associated (>75% agreement) with long-term opioid use, including benzodiazepine use, comorbidity scores, (generally undefined) substance misuse, tobacco use, and low income. However, studies were mostly consistent that alcohol abuse and healthcare utilization were not associated with long-term opioid use. Gender, age among older adults, Black race, dementia, rural/nonurban residence, prescription of long-acting opioids, unmarried status, and use of muscle relaxants were variably associated (<75% agreement) with long-term opioid use.

Six studies examined factors associated with opioid-related disorders, although only one study evaluated factors associated with opioid use disorder. Alcohol misuse and gender were variably associated with opioid misuse (examined by three studies each).

All other evaluations of specific pairs of associated factors and outcomes of interest were evaluated by only one or two studies each. These included analyses of factors associated with multiple opioid prescribers, mental health outcomes, physical health outcomes, all-cause hospitalization, opioid-related hospitalization, nonopioid-specific hospitalization, emergency department visits, opioid overdose, all-cause death, opioid-related death, and nonopioid-related death.

The evidence on interventions directed at older adults is sparse. Of the 16 studies of opioid-related interventions in older adults, six examined screening tools to predict opioid-related harms, but none of these tools was tested in clinical practice to assess real-world results. Two studies found that prescription drug monitoring programs are associated with less opioid use in communities. Other studied interventions include multidisciplinary pain education for patients, an educational pamphlet for patients, implementation of an opioid safety initiative, provision of patient information and pain management training for clinicians, a bundle of educational modalities for clinicians, free prescription acetaminophen, a nationally mandated tamper-resistant opioid formulation, and motivational interview training for nursing students. Few intervention studies evaluated pain or other patient-centered outcomes such as disability and functioning.

Conclusions. The evidence base that is directly applicable to older adults who are prescribed opioids or have opioid-related disorders is limited. Fundamental research is necessary to determine which factors may predict clinically important, patient-centered, opioid-related outcomes. Studies to date have identified numerous possible factors associated with long-term opioid use (whether appropriate or not), but analyses of other opioid-related outcomes in older adults are relatively sparse. Research is also needed to identify interventions to reduce opioid prescribing where harms outweigh benefits (including screening tools), reduce opioid-related harms and disorders, and treat existing misuse or opioid use disorder among older adults.

 

Keywords 
RISEOK opioids elderly patients elderly Elderly care older adults
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