Long-term Opioids For Chronic Pain Research Articles

Stimulant use and opioid-related harm in patients on long-term opioids for chronic pain

BackgroundThere is lack of clarity regarding the impact of and optimal clinical response to stimulant use among people prescribed long-term opioid therapy (LTOT) for pain. ObjectiveTo determine if a positive urine drug test (UDT) for stimulants was associated with subsequent opioid-related harm or discontinuation of LTOT. DesignRetrospective cohort study. PatientsPeople living with and without HIV living in a major metropolitan area with public insurance, prescribed LTOT for chronic, non-cancer pain (n=600). Main measuresUDT results from January 2012 to June 2019 were evaluated against 1) opioid-related emergency department (ED) visits (oversedation, constipation, infections associated with injecting opioids, and opioid seeking) or death in each 90-day period following a UDT, using logistic regression, and 2) LTOT discontinuation. ResultsThere were no opioid overdose deaths within 90 days following a stimulant-positive UDT. A stimulant-positive UDT was not statistically significantly associated with opioid-related ED visits within 90 days (adjusted odds ratio [aOR] 1.39; 95% CI=0.88–2.21). Stimulant-positive UDT was independently associated with subsequent discontinuation of LTOT within 90 days (aOR 2.96; 95% CI=2.13 – 4.12). Living with HIV was independently associated with decreased odds of LTOT discontinuation (aOR 0.65; 95% CI 0.43 – 0.99). ConclusionsDespite no association between a stimulant-positive UDT and subsequent opioid-related harm, there was an association with subsequent LTOT discontinuation, with heterogeneity across clinical groups. Detection of stimulant use should result in a discussion of substance use and risk, rather than reflex LTOT discontinuation.

Economic Evaluation: A Randomized Pragmatic Trial of a Primary Care-based Cognitive Behavioral Intervention for Adults Receiving Long-term Opioids for Chronic Pain.

Chronic pain is prevalent and costly; cost-effective nonpharmacological approaches that reduce pain and improve patient functioning are needed. Report the incremental cost-effectiveness ratio (ICER), compared with usual care, of cognitive behavioral therapy aimed at improving functioning and pain among patients with chronic pain on long-term opioid treatment. Economic evaluation conducted alongside a pragmatic cluster randomized trial. Adults with chronic pain on long-term opioid treatment (N=814). A cognitive behavioral therapy intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorists, nurses) with additional support from physical therapists, and pharmacists. Cost per quality adjusted life year (QALY) gained, and cost per additional responder (≥30% improvement on standard scale assessment of Pain, Enjoyment, General Activity, and Sleep). Costs were estimated as-delivered, and replication. Per patient intervention replication costs were $2145 ($2574 as-delivered). Those costs were completely offset by lower medical care costs; inclusive of the intervention, total medical care over follow-up was $1841 lower for intervention patients. Intervention group patients also had greater QALY and responder gains than did controls. Supplemental analyses using pain-related medical care costs revealed ICERs of $35,000, and $53,000 per QALY (for replication, and as-delivered intervention costs, respectively); the ICER when excluding patients with outlier follow-up costs was $106,000. Limited to 1-year follow-up; identification of pain-related utilization potentially incomplete. The intervention was the optimal choice at commonly accepted levels of willingness-to-pay for QALY gains; this finding was robust to sensitivity analyses.

Evaluation of Buprenorphine Rotation in Patients Receiving Long-term Opioids for Chronic Pain

Individuals with chronic pain who use long-term opioid therapy (LTOT) are at risk of opioid use disorder and other harmful outcomes. Rotation to buprenorphine may be considered, but the outcomes of such rotation in this population have not been systematically reviewed. To synthesize the evidence on rotation to buprenorphine from full μ-opioid receptor agonists among individuals with chronic pain who were receiving LTOT, including the outcomes of precipitated opioid withdrawal, pain intensity, pain interference, treatment success, adverse events or adverse effects, mental health condition, and health care use. PubMed, CINAHL, Embase, and PsycInfo were searched from inception through November 3, 2020, for peer-reviewed original English-language research that reported the prespecified outcomes of rotation from prescribed long-term opioids to buprenorphine among individuals with chronic pain. Two independent reviewers extracted data as well as assessed risk of bias and study quality according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A total of 22 studies were analyzed, of which 5 (22.7%) were randomized clinical trials, 7 (31.8%) were case-control or cohort studies, and 10 (45.5%) were uncontrolled pre-post studies, which involved 1616 unique participants (675 female [41.8%] and 941 male [58.2%] individuals). Six of the 22 studies (27.3%) were primary or secondary analyses of a large randomized clinical trial. Participants had diverse pain and opioid use histories. Rationale for buprenorphine rotation included inadequate analgesia, intolerable adverse effects, risky opioid regimens (eg, high dose and/or sedative coprescriptions), and aberrant opioid use. Most protocols were adapted from protocols for initiating treatment in patients with opioid use disorder and used buccal or sublingual buprenorphine. Very low-quality evidence suggested that buprenorphine rotation was associated with maintained or improved analgesia, with a low risk of precipitating opioid withdrawal. Steady-dose buprenorphine was better tolerated than tapered-dose buprenorphine. Adverse effects were manageable, and severe adverse events were rare. Only 2 studies evaluated mental health outcomes, but none evaluated health care use. Limitations included a high risk of bias in most studies. In this systematic review, buprenorphine was associated with reduced chronic pain intensity without precipitating opioid withdrawal in individuals with chronic pain who were receiving LTOT. Future studies are necessary to ascertain the ideal starting dose, formulation, and administration frequency of buprenorphine as well as the best approach to buprenorphine rotation.

Complementary, Integrative, and Nondrug Therapy Use for Pain Among US Military Veterans on Long-term Opioids.

Long-term opioid therapy for chronic pain arose amid limited availability and awareness of other pain therapies. Although many complementary and integrative health (CIH) and nondrug therapies are effective for chronic pain, little is known about CIH/nondrug therapy use patterns among people prescribed opioid analgesics. The objective of this study was to estimate patterns and predictors of self-reported CIH/nondrug therapy use for chronic pain within a representative national sample of US military veterans prescribed long-term opioids for chronic pain. National two-stage stratified random sample survey combined with electronic medical record data. Data were analyzed using logistic regressions and latent class analysis. US military veterans in Veterans Affairs (VA) primary care who received ≥6 months of opioid analgesics. Self-reported use of each of 10 CIH/nondrug therapies to treat or cope with chronic pain in the past year: meditation/mindfulness, relaxation, psychotherapy, yoga, t'ai chi, aerobic exercise, stretching/strengthening, acupuncture, chiropractic, massage; Brief Pain Inventory-Interference (BPI-I) scale as a measure of pain-related function. In total, 8891 (65%) of 13,660 invitees completed the questionnaire. Eighty percent of veterans reported past-year use of at least 1 nondrug therapy for pain. Younger age and female sex were associated with the use of most nondrug therapies. Higher pain interference was associated with lower use of exercise/movement therapies. Nondrug therapy use patterns reflected functional categories (psychological/behavioral, exercise/movement, manual). Use of CIH/nondrug therapies for pain was common among patients receiving long-term opioids. Future analyses will examine nondrug therapy use in relation to pain and quality of life outcomes over time.

The evaluating prescription opioid changes in veterans (EPOCH) study: Design, survey response, and baseline characteristics.

In the United States (US), long-term opioid therapy has been commonly prescribed for chronic pain. Since recognition of the opioid overdose epidemic, clinical practice guidelines have recommended tapering long-term opioids to reduced doses or discontinuation. The Effects of Prescription Opioid Changes for veterans (EPOCH) study is a national population-based prospective observational study of US Veterans Health Administration primary care patients designed to assess effects of evolving opioid prescribing practice on patients treated with long-term opioids for chronic pain. A stratified random sampling design was used to identify a survey sample from the target population of patients treated with opioid analgesics for ≥ 6 months. Demographic, diagnostic, visit, and pharmacy dispensing data were extracted from existing datasets. A 2016 mixed-mode mail and telephone survey collected patient-reported data, including the main patient-reported outcomes of pain-related function (Brief Pain Inventory interference; BPI-I scores 0-10, higher scores = worse) and health-related quality of life. Data on survey participants and non-participants were analyzed to assess potential nonresponse bias. Weights were used to account for design. Linear regression models were used to assess cross-sectional associations of opioid treatment with patient-reported measures. Of 14,160 patients contacted, 9253 (65.4%) completed the survey. Participants were older than non-participants (63.9 ± 10.6 vs. 59.6 ± 13.0 years). The mean number of bothersome pain locations was 6.8 (SE 0.04). Effectiveness of pain treatment and quality of pain care were rated fair or poor by 56.1% and 45.3%, respectively. The opioid daily dosage range was 1.6 to 1038.2 mg, with mean = 50.6 mg (SE 1.1) and median = 30.9 mg (IQR 40.7). Among the 73.2% of patients who did not receive long-acting opioids, the mean daily dosage was 30.4 mg (SE 0.6) and mean BPI-I was 6.4 (SE 00.4). Among patients who received long-acting opioids, the mean daily dosage was 106.2 mg (SE 2.8) and mean BPI-I was 6.8 (SE 0.07). Higher daily dosage was associated with worse pain-related function and quality of life among patients without long-acting opioids, but not among patients with long-acting opioids. Future analyses will use follow-up data to examine effects of opioid dose reduction and discontinuation on patient outcomes.

Disagreement and Uncertainty Among Experts About how to Respond to Marijuana Use in Patients on Long-term Opioids for Chronic Pain: Results of a Delphi Study.

Marijuana use is common among patients on long-term opioid therapy (LTOT) for chronic pain, but there is a lack of evidence to guide clinicians' response. To generate expert consensus about responding to marijuana use among patients on LTOT. Analysis from an online Delphi study. Clinician experts in pain and opioid management across the United States. Participants generated management strategies in response to marijuana use without distinction between medical and nonmedical use, then rated the importance of each management strategy from 1 (not at all important) to 9 (extremely important). A priori rules for consensus were established, and disagreement was explored using cases. Thematic analysis of free-text responses examined factors that influenced participants' decision-making. Of 42 participants, 64% were internal medicine physicians. There was consensus that it is not important to taper opioids as an initial response to marijuana use. There was disagreement about the importance of tapering opioids if there is a pattern of repeated marijuana use without clinical suspicion for a cannabis use disorder (CUD) and consensus that tapering is of uncertain importance if there is suspicion for CUD. Three themes influenced experts' perceptions of the importance of tapering: 1) benefits and harms of marijuana for the individual patient, 2) a spectrum of belief about the overall riskiness of marijuana use, and 3) variable state laws or practice policies. Experts disagree and are uncertain about the importance of opioid tapering for patients with marijuana use. Experts were influenced by patient factors, provider beliefs, and marijuana policy, highlighting the need for further research.

Objective evidence of severe disease: opioid use in chronic pain.

Treating chronic pain presents numerous challenges. First, assessing patients with chronic pain is complicated by the lack of objective measures of pain itself. Chronic pain guidelines already developed by national organizations rely on careful history taking rather than objective measures. Second, opioids are an accepted element of chronic pain management, but their use is tempered by risks of overdose, dependency, and the potential for diversion. This essay proposes a new standard for the use of long-term opioids for chronic pain: the presence or absence of objective evidence of severe disease. This standard, which supports responsible prescribing of opioids, is one that clinicians can understand and apply when considering prescribing long-term opioids for chronic pain. Until we have measures of pain itself, we should insist upon objective evidence of severe disease before prescribing opioids for chronic pain.