Non-opioid Treatments Research Articles

Paracetamol versus ibuprofen for early postpartum pain control: a randomized controlled trial.

To evaluate the effectiveness of paracetamol and ibuprofen as non-opioid treatments for postpartum pain control after vaginal delivery. This randomized controlled study at a university-affiliated medical center involved parturient who received blindly oral tablets of either 1000 mg of paracetamol or 400 mg of ibuprofen, post-vaginal birth. Pain levels were assessed using a numeric rating scale (NRS) at four time points: before treatment, and 1, 4, and 6 h post-treatment (T0, T1, T4, and T6, respectively). We also compared the need for additional analgesia, breastfeeding initiation, mobilization, and urination following the delivery between the groups. To ensure statistical power, the study was designed to detect differences of one point on the NRS with at least 37 women per group. A total of 107 women participated, including paracetamol (n = 52) and ibuprofen (n = 55) groups. Demographics and perinatal outcomes were similar across groups. No significant differences were found in the interval between delivery and request for pain control (8 ± 6-10.5 and 11 ± 6-16h for the paracetamol and the ibuprofen, respectively, P = .13). Pain levels on the NRS were similar for both groups at all intervals. There were also no group differences in the time to the initiation of breastfeeding, mobilization, urination, or the need for additional analgesia. Both, paracetamol and ibuprofen, can be considered equivalent and effective non-opioid alternatives for postpartum pain control. REGISTRY AT CLINICALTRIALS.GOV: (NCT04653506), https://register. gov/prs/beta/studies/S000AFOR00000066/recordSummary .

Do veterans with risky substance use (RSU) use distinct pain treatment modalities?

Risky substance use (RSU) is common among people with chronic pain and is associated with worse pain treatment outcomes. Nonopioid treatment is recommended, but it is unknown whether people with RSU use different or fewer pain treatment modalities. This study describes use of different pain treatments by veterans with and without RSU and those receiving versus not receiving opioid medication. Veterans (N = 924) who filed service-connected disability claims related to musculoskeletal conditions and rated their pain four or higher on the Numeric Rating Scale, reported on 25 different pain services in the preceding 90 days. Recent RSU was identified via Alcohol, Smoking, and Substance Involvement Test (ASSIST) cutoffs and/or nail sample toxicology. Overall, RSU was not associated with number of provider-delivered or self-delivered pain modalities. Over-the-counter medications (71%), self-structured exercise (69%), and nonopioid prescription medications (38%) were the most used modalities. Veterans receiving prescribed opioids (8.4%) were more likely to see primary care, receive injections, and attend exercise and/or meditation classes, compared to those without opioid prescriptions. Opioid and nonopioid pain treatment utilization did not differ based on RSU, and those prescribed opioids were more likely to engage in other nonopioid pain treatments. Regardless of RSU, veterans appear willing to try provider-delivered (58%) and self-delivered (79%) pain treatment. In this first-ever evaluation of 25 different pain treatment modalities among veterans with and without RSU, people with RSU did not use less treatment modalities.

Evaluation of postoperative delirium in geriatric patients given acetaminophen with and without melatonin: A retrospective cohort study.

Postoperative delirium has many consequences and should be prevented when possible. Non-opioid pain treatments have known delirium prevention benefits, while melatonin has promising prevention data in non-surgical populations. The incidence of postoperative delirium was retrospectively compared in patients prescribed acetaminophen with and without melatonin following orthopedic surgery. Retrospective data was analyzed in adults ≥65-years-old who were hospitalized within one health system following an orthopedic procedure. Patients receiving at least acetaminophen 1000mg/day with and without melatonin 1mg/day for at least 48hours perioperatively were included. Patients were excluded if they had prior delirium, an intensive care unit placement >24hours, or other risk factors for developing delirium to reduce confounders. The primary outcome was delirium incidence or positive CAM-ICU score. Key secondary endpoints included hospital length of stay and 30-day hospital readmission. Two hundred patients were assessed, and 134 patients were included in the analysis (ie, 66 acetaminophen plus melatonin, 68 acetaminophen alone). There was a lower rate of delirium when comparing the combination vs acetaminophen alone (5% vs 25%; P = 0.001). There were no differences in 30-day readmission. Patients taking the combination had a longer length of stay than acetaminophen alone (5 vs 4 days; P = 0.04). Geriatric patients taking acetaminophen plus melatonin after orthopedic surgery had a significantly lower risk of delirium than patients receiving acetaminophen alone. Using combination melatonin and acetaminophen before orthopedic surgery is a promising delirium prevention strategy and should be considered in future prospective trials.

Explorations of Agonist Selectivity for the α9* nAChR with Novel Substituted Carbamoyl/Amido/Heteroaryl Dialkylpiperazinium Salts and Their Therapeutic Implications in Pain and Inflammation.

There is an urgent need for nonopioid treatments for chronic and neuropathic pain to provide effective alternatives amid the escalating opioid crisis. This study introduces novel compounds targeting the α9 nicotinic acetylcholine receptor (nAChR) subunit, which is crucial for pain regulation, inflammation, and inner ear functions. Specifically, it identifies novel substituted carbamoyl/amido/heteroaryl dialkylpiperazinium iodides as potent agonists selective for human α9 and α9α10 over α7 nAChRs, particularly compounds 3f, 3h, and 3j. Compound 3h (GAT2711) demonstrated a 230 nM potency as a full agonist at α9 nAChRs, being 340-fold selective over α7. Compound 3c was 10-fold selective for α9α10 over α9 nAChR. Compounds 2, 3f, and 3h inhibited ATP-induced interleukin-1β release in THP-1 cells. The analgesic activity of 3h was fully retained in α7 knockout mice, suggesting that analgesic effects were potentially mediated through α9* nAChRs. Our findings provide a blueprint for developing α9*-specific therapeutics for pain.

Abstract PO1-09-07: Outpatient mastectomy is a safe surgical option for patients treated in a rural Appalachian tertiary facility

Abstract Background The feasibility of the outpatient mastectomy in a rural setting is poorly characterized. Centers treating rural patient populations have unique challenges. Limited access to resources and distance to facilities that can care for post-surgical patients are two such challenges. The aim of this study is to analyze the efficacy and safety of an outpatient mastectomy program in our tertiary care facility treating rural Appalachian patients. Methods We performed a single-institution retrospective review of all patients with breast cancer over 18 years of age who underwent a mastectomy with or without immediate alloplastic breast reconstruction at JW Ruby Memorial Hospital from 2019-2022. Our primary objective was to determine the 30, 60, and 90-day readmission rates. Our secondary objective included an analysis of perioperative pain control variables to develop an enhanced recovery protocol. Data collected included age, ethnicity, prognostic factors, stage at diagnosis, surgical treatment, opioid and non-opioid based treatments pre- and postoperatively by milligram morphine equivalents (MMEs), comorbidities as analyzed by the Charlson comorbidity index (CCI) variables, and distance from the tertiary hospital. Results We identified thirty-two women between 2019-2022 who underwent same-day mastectomy at JW Ruby Memorial Hospital in Morgantown, West Virginia. The mean age was 55.4 years. The mean distance to the hospital was 22.1 miles with a maximum distance of 111 miles (SEM = 3.90). The mean CCI score was 2.9 (SEM = 0.51). Overall readmission rates at 30- 60- and 90-days were 6.3% (n = 2), 3.1% (n = 1) and 0%, respectively. One woman was readmitted eight days postoperatively from a unilateral mastectomy and sentinel lymph node biopsy without reconstruction for an expanding hematoma of the chest after resuming anticoagulation on postoperative day three. The other two patients were admitted for unrelated surgical reasons. Thus, readmission related to surgical complications alone was 3.1% (n = 1). Preoperatively, 90.6% (n = 29) of women received a local anesthetic block by the anesthesia provider. Neither a preoperative nor intraoperative block was given to the remaining three. Bilateral mastectomies occurred in 21.9% (n = 7) of women and 78.1% (n = 25) underwent unilateral mastectomy. Of these 32 women, 25.0% (n = 8) underwent immediate staged reconstruction with tissue expanders. There were no direct-to-implant reconstructions in this population. There were twenty-six sentinel lymph node biopsies and four axillary dissections performed. The mean MMEs received for the duration of the hospital encounter was 132 (SEM = 23.4). An enhanced recovery after surgery protocol was not used. Discussion Outpatient mastectomy is a safe and effective option for eligible patients living in rural settings. Factors such as the type of mastectomy, reconstruction, the patient's overall health status, and the availability of support at home can impact the feasibility of this approach. Careful patient selection and a multidisciplinary team including the patient, surgeon, and anesthesiologist should carefully assess the individual’s circumstances to determine if outpatient mastectomy is appropriate. Implementation of enhanced recovery after surgery protocols will be further investigated and guided by this study. Citation Format: Gregory Stimac, Kristin Lupinacci, Michael Cowher, Hannah Hazard-Jenkins. Outpatient mastectomy is a safe surgical option for patients treated in a rural Appalachian tertiary facility [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-07.

Sleep and Pain in Veterans with Chronic Pain: Effects of Psychological Pain Treatment and Temporal Associations.

Chronic pain is highly prevalent in US military Veterans. Non-opioid and non-pharmacologic treatments are recommended when clinically appropriate, but research on the mechanisms underlying benefits of these treatments is lacking. Here, we examined the role of sleep in the effects of three non-pharmacologic pain treatments in Veterans. Specifically, we investigated whether treatment effects on sleep predicted treatment effects on pain occurring later, or vice versa. Veterans enrolled in a randomized controlled trial were invited to participate in this supplementary sleep study. A total of 174 Veterans were randomized to one of three 8-session, in-person, group-based pain treatments: hypnosis, mindfulness meditation, or education control. Measurements included self-reported sleep disturbance, pain intensity, and pain catastrophizing; sleep duration was assessed with actigraphy. Sleep and pain measurements were obtained at baseline, posttreatment, and 3-month posttreatment follow-up. At baseline, average pain intensity was moderate (mean ± SD: 5.7 ± 1.7 on the 0-10 Numeric Rating Scale), pain catastrophizing was just below the clinically relevant threshold (mean ± SD: 28.6 ± 12.2 on the Pain Catastrophizing Scale), and subjective sleep disturbance exceeded the US population average (mean ± SD: 58.5 ± 8.1 on the Patient Reported Outcomes Measurement Information System Sleep Disturbance - Short Form). By contrast, objective sleep duration was consistent with the recommended daily sleep amount of 7-8 h for adults (mean ± SD: 8.3 ± 1.4 h). Across treatment conditions, pain intensity, pain catastrophizing, and subjective sleep disturbance were significantly less at posttreatment and 3-month follow-up than at baseline (p < 0.001). Actigraphic sleep duration did not differ significantly as a function of time. There was a high degree of covariation among the measures of pain intensity, pain catastrophizing, and sleep disturbance (p < 0.05). However, self-reported sleep disturbance was not significantly correlated with actigraphic sleep duration (|r| <= 0.13, p > 0.05). Sleep and pain variables observed at prior assessments predicted these same variables at subsequent assessments. There was no significant evidence that changes in pain preceded changes in sleep or that changes in sleep preceded changes in pain (all p > 0.05). For this study's Veterans, treatment-related changes in sleep and pain appeared to occur in parallel. The concomitant changes in sleep and pain suggest that therapies improving pain in Veterans may yield attendant benefits for the treatment of sleep, and possibly vice versa.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis

Objective To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. Methods Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. Results Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. Conclusions Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Morphine Withdrawal-Induced Hyperalgesia in Models of Acute and Extended Withdrawal Is Attenuated by l-Tetrahydropalmatine.

Effective pain control is an underappreciated aspect of managing opioid withdrawal, and its absence presents a significant barrier to successful opioid detoxification. Accordingly, there is an urgent need for effective non-opioid treatments to facilitate opioid detoxification. l-Tetrahydropalmatine (l-THP) possesses powerful analgesic properties and is an active ingredient in botanical formulations used in Vietnam for the treatment of opioid withdrawal syndrome. In this study, rats receiving morphine (15 mg/kg, i.p.) for 5 days per week displayed a progressive increase in pain thresholds during acute 23 h withdrawal as assessed by an automated Von Frey test. A single dose of l-THP (5 or 7.5 mg/kg, p.o.) administered during the 4th and 5th weeks of morphine treatment significantly improves pain tolerance scores. A 7-day course of l-THP treatment in animals experiencing extended withdrawal significantly attenuates hyperalgesia and reduces the number of days to recovery to baseline pain thresholds by 61% when compared to vehicle-treated controls. This indicates that the efficacy of l-THP on pain perception extends beyond its half-life. As a non-opioid treatment for reversing a significant hyperalgesic state during withdrawal, l-THP may be a valuable addition to the currently limited arsenal of opioid detoxification treatments.

Effect of light needle in the treatment of opioid use disorder: A protocol for a randomized controlled trial

Opioid use disorder occurs worldwide and creates an increasing economic burden and public health crisis. Some problems are associated with using opioid agonists; therefore, there is a need to develop non-opioid treatments to improve acute and long-term opioid withdrawal syndromes. We will enroll 100 participants with opioid use disorders receiving methadone maintenance treatment at an addiction treatment center and randomly allocate them to an experimental or control group. The experimental group will receive 12 sessions of light needle therapy within 4 weeks, while the control group will receive sham light needle treatment without any laser output. Urinary morphine levels were assessed before and after treatment. Participants will be asked to self-report their number of episodes or days of heroin use and heroin craving/refusal to use heroin in the previous week before and after treatment on a visual analogue scale score of 0 to 10. Quality of life will be reported using the Short Form-12v2 before and after 4 weeks of treatment. Pulse diagnosis and heart rate variability will be evaluated before and after treatment. Baseline patient characteristics will be compared between the groups using the independent t test and the χ2 test. Data between the 2 groups will be compared using generalized estimation equations, and paired t tests. This study aims to investigate the effect of adjuvant light needle therapy in patients with opioid use disorder on methadone maintenance treatment.

Chronic low back pain comorbidity count and its impact on exacerbating opioid and non-opioid prescribing behavior.

The objective of the study was to determine the characteristics of chronic low back pain (CLBP) comorbidity and its impact on opioid and non-opioid treatments among Chicagoland patients with CLBP. A retrospective cross-sectional study comparing differences in comorbidity and treatment patterns among Chicagoland patients with CLBP against a matched control arm without chronic low back pain (NCLBP). Academic hospital system outpatient services. Using the International Classification of Diseases, 10th Revision codes (ICD 10) 9589 patients were identified with CLBP with a median age of 57 years old and 62.32% female distribution. The NCLBP group comprised 9589 age-, sex-, race-, and region-matched patients. An increased prevalence across all 17 studied comorbidities was found in CLBP patients as compared to NCLBP patients. CLBP patients carried an average of 3.5 comorbidities compared with 2.4 comorbidities in NCLBP patients. Rheumatoid arthritis (RA), joint arthritis, and obesity had the strongest relationship with CLBP. Additionally, we found that the most prescribed treatment for CLBP were opioids, which ranked above NSAIDs and physical therapy. 56% of CLBP patients were prescribed opioids as compared to 36% of NCLBP patients (Odds Ratio=2.28, 95% CI: 2.16-2.42). Tramadol was the agent with the strongest relationship to CLBP. CLBP patients were more likely to use two or more opioids concomitantly. The number of total treatments was positively associated with the number of comorbidities in both CLBP and NCLBP patients (Cochran-Armitage trend test p < 0.0001). Chronic low back pain patients showed a higher number of comorbidities than their NCLBP counterparts. Comorbidity count trended positively with higher treatment burden with opioids being the most prescribed treatment, often with poly-opioid use, over conservative modalities such as NSAIDs and physical therapy.

Patient and Provider Perspectives on Benefits and Harms of Continuing, Tapering, and Discontinuing Long-Term Opioid Therapy.

Given efforts to taper patients off long-term opioid therapy (LTOT) because of known harms, it is important to understand if patients and providers align in LTOT treatment goals. To investigate patient and provider perceptions about the harms and benefits of continuing and discontinuing LTOT. Qualitative study PARTICIPANTS: Patients and providers with experiences with LTOT for pain in two Veterans Health Affairs regions. We conducted semi-structured interviews and analyzed data using rapid qualitative analysis to describe patient and provider preferences about LTOT continuation and discontinuation and non-opioid pain treatments. Participants (n=43) included 28/67 patients and 15/17 providers. When discussing continuing LTOT, patients emphasized the benefits outweighed the harms, whereas providers emphasized the harms. Participants agreed on the benefits of continuing LTOT for improved physical functioning. Provider-reported benefits of continuing LTOT included maintaining the status quo for patients without opioid alternatives or who were at risk for illicit drug use. Participants were aligned regarding the harms of negative side-effects (e.g., constipation) from continued LTOT. In contrast, when discussing LTOT tapering and discontinuation, providers underscored how benefits outweighed the harms, citing patients' improved well-being and pain management with tapering or alternatives. Patients did not foresee benefits to potential LTOT tapers or discontinuation and were worried about pain management in the absence of LTOT. When discussing non-opioid pain treatments, participants emphasized that they were adjunctive to opioid therapy rather than a replacement (except for cannabis). Providers described the importance of mental health services to manage pain, which differed from patients who focused on treatments to improve strength and mobility and reduce pain. Patients emphasized the benefits of continuing LTOT for pain management and well-being, which differed from providers' emphasis on the benefits of discontinuing LTOT. Patient and provider differences are important for informing patient-centered care and decisions around continuing, tapering, or discontinuing LTOT.

Provider beliefs about the ideal design of an opioid deprescribing and substitution intervention for older adults.

Opportunities exist to meaningfully reduce suboptimal prescription opioid use among older adults. Deprescribing is one possible approach to reducing suboptimal use. Appropriate interventions should outline how to carefully taper opioids, closely monitor adverse events, substitute viable alternative and affordable nonopioid pain treatments, and initiate medications for opioid use disorder to properly manage use disorders, as needed. We sought to document and understand provider perceptions to begin developing effective and safe opioid deprescribing interventions. We conducted 3 semistructured focus groups that covered topics such as participant perspectives on opioid deprescribing in older adults, how to design an ideal intervention, and how to identify potential barriers or facilitators in implementing an intervention. Focus group transcripts were double coded and qualitatively analyzed to identify overarching themes. Healthcare providers (n = 17), including physicians, pharmacists, nurses, social workers, and administrative staff, participated in 3 focus groups. We identified 4 key themes: (1) involve pharmacists in deprescribing and empower them as leaders of an opioid deprescribing service; (2) ensure tight integration and close collaboration throughout the deprescribing process from the inpatient to outpatient settings; (3) more expansive inclusion criteria than age alone; and (4) provision of access to alternative pharmacological and nonpharmacological pain management modalities to patients. Our findings, which highlight various healthcare provider beliefs about opioid deprescribing interventions, are expected to serve as a framework for other organizations to develop and implement interventions. Future studies should incorporate patients' and family caregivers' perspectives.

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial.

BackgroundNeuropathic pain (NP), a complication of several conditions (eg, diabetic neuropathy and varicella zoster), is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity in NP conditions is often worse at night. The pineal hormone melatonin has been shown to reduce pain in both preclinical and clinical settings, in addition to multiple trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome.ObjectiveWe propose to conduct a clinical trial to evaluate the efficacy and safety of melatonin for NP.MethodsUsing a double-blind, placebo-controlled, crossover design, 30 adults with NP will be randomly allocated to one of two sequences of treatment with melatonin and placebo. During each of the two treatment periods, participants will take capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome will be mean daily pain intensity (scored 0-10) at maximally tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTDs, will include global improvement, adverse events, mood, and quality of life.ResultsThis trial was registered in the International Standard Randomized Controlled Trial registry May 4, 2022 (ISRCTN #16215617), attained conditional ethics approval May 9, 2022 (Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-387-22), and recruitment is set to start August 2022.ConclusionsThis trial will provide rigorous evidence comparing the efficacy of melatonin to that of placebo in the treatment of NP.Trial RegistrationISRCTN Registry 16215617; https://www.isrctn.com/ISRCTN16215617International Registered Report Identifier (IRRID)PRR1-10.2196/40025

Effects of Opioid Prescribing Cap Laws on Opioid and Other Pain Treatments Among Persons with Chronic Pain.

Many states have adopted laws that limit the amount or duration of opioid prescriptions. These limits often focus on prescriptions for acute pain, but there may be unintended consequences for those diagnosed with chronic pain, including reduced opioid prescribing without substitution of appropriate non-opioid treatments. To evaluate the effects of state opioid prescribing cap laws on opioid and non-opioid treatment among those diagnosed with chronic pain. We used a difference-in-differences approach that accounts for staggered policy adoption. Treated states included 32 states that implemented a prescribing cap law between 2017 and 2019. A total of 480,856 adults in the USA who were continuously enrolled in medical and pharmacy coverage from 2013 to 2019 and diagnosed with a chronic pain condition between 2013 and 2016. Among individuals with chronic pain in each state: proportion with at least one opioid prescription and with prescriptions of a specific duration or dose, average number of opioid prescriptions, average opioid prescription duration and dose, proportion with at least one non-opioid chronic pain prescription, average number of such prescriptions, proportion with at least one chronic pain procedure, and average number of such procedures. State laws limiting opioid prescriptions were not associated with changes in opioid prescribing, non-opioid medication prescribing, or non-opioid chronic pain procedures among patients with chronic pain diagnoses. These findings do not support an association between state opioid prescribing cap laws and changes in the treatment of chronic non-cancer pain.

Opioid agonist treatment for people who are dependent on pharmaceutical opioids.

There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment). We used standard Cochrane methods. We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms. There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.

PRescribing Interventions for Chronic pain using the Electronic health record (PRINCE): Study protocol

BackgroundPrimary care is a frequent source of pain treatment and opioid prescribing. The objective of the Prescribing Interventions for Chronic Pain using the Electronic health record (PRINCE) study is to assess the effects of two behavioral economics-informed interventions embedded within the electronic health record (EHR) on guideline-concordant pain treatment and opioid prescribing decisions in primary care settings. MethodsSetting: The setting for this study is 43 primary care clinics in Minnesota.Design: The PRINCE study uses a cluster-randomized 2 × 2 factorial design to test the effects of two interventions. An adaptive design allows for the possibility of secondary randomization to test if interventions can be titrated while maintaining efficacy.Interventions: One intervention alters the “choice architecture” within the EHR to nudge clinicians toward non-opioid treatments for opioid-naïve patients and toward tapering for patients currently receiving a “high risk” opioid. The other intervention integrates the prescription drug monitoring program (PDMP) directly within the EHR.Outcome: The primary outcome for opioid-naïve patients is whether an opioid is prescribed in a primary care visit without a non-opioid alternative pain treatment. The primary outcome for current opioid-using patients is whether opioid prescriptions were tapered with a documented rationale. DiscussionThe PRINCE study will provide real-world evidence on two approaches to improving pain treatment in primary care using the EHR. The adaptive study design strikes a balance between establishing intervention efficacy and testing whether efficacy varies with intervention intensity.

Trends in opioid and non-opioid treatment for chronic non-cancer pain and cancer pain among privately insured adults in the United States, 2012-2019.

Recent clinical guidelines have emphasized non-opioid treatments in lieu of prescription opioids for chronic non-cancer pain, exempting cancer patients from these recommendations. In this study, we determine trends in opioid and non-opioid treatment among privately insured adults with chronic non-cancer pain (CNCP) or cancer. Using administrative claims data from IBM MarketScan Research Databases, we identified privately-insured adults who were continuously enrolled in insurance for at least one calendar year from 2012 to 2019. We identified individuals with CNCP diagnosis, defined as a diagnosis of arthritis, headache, low back pain, and/or neuropathic pain, and a individuals with cancer diagnosis in a calendar year. Outcomes included receipt of any opioid, non-opioid medication, or non-pharmacologic CNCP therapy and opioid prescribing volume, MME-per-day, and days’ supply. Estimates were regression-adjusted for age, sex, and region. Between 2012 and 2019, the proportion of patients who received any opioid decreased across both groups (CNCP: 49.7 to 30.5%, p<0.01; cancer: 86.0 to 78.7%, p<0.01). Non-opioid pain medication receipt remained steady for individuals with CNCP (66.7 to 66.4%, p<0.01) and increased for individuals with cancer (74.4 to 78.8%, p<0.01), while non-pharmacologic therapy use rose among individuals with CNCP (62.4 to 66.1%, p<0.01). Among those prescribed opioids, there was a decrease in the receipt of at least one prescription with >90 MME/day (CNCP: 13.9% in 2012 to 4.9% in 2019, p<0.01; Cancer: 26.2% to 7.6%, p<0.01); >7 days of supply (CNCP: 56.3% to 30.7%, p <0.01; Cancer: 47.5% to 22.7%, p<0.01), the mean number of opioid prescriptions (CNCP: 5.2 to 3.9, p<0.01; Cancer: 4.0 to 2.7, p<0.01) and mean MME/day (CNCP: 49.9 to 38.0, p<0.01; Cancer: 62.4 to 44.7, p<0.01). Overall, from 2012–2019, opioid prescribing declined for CNCP and cancer, with larger reductions for patients with CNCP. For both groups, reductions in prescribed opioids outpaced increases in non-opioid alternatives.

Nonadherence to Clinical Practice Guidelines for Opioid Prescribing in Patients with Chronic Low Back Pain: A Pain Research Registry–Based Study

This study measured the prevalence and impact of nonadherence to clinical practice guidelines (CPGs) that recommend using nonpharmacological and nonopioid treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) before considering opioids in patients with chronic low back pain. Participants within the PRECISION Pain Research Registry provided data during the period from April 2016 through October 2021. The prevalence of nonadherence to CPGs was based on current or prior use of 6 common nonpharmacological treatments, NSAIDs, and opioids for low back pain. The primary outcome measures were low back pain intensity, back-related disability, and pain impact on health-related quality of life. The prevalence of nonadherence to CPGs was 68 (18.0%) participants among the 378 participants currently using opioids. Participants having some post-high school education (OR, 0.41; 95% CI, 0.22-0.74) or at least a college education (OR, 0.26; 95% CI, 0.12-0.56) were at decreased risk of treatment that was nonadherent to CPGs in a multivariate analysis. Participants whose treatment was nonadherent to CPGs reported significantly worse clinical outcomes across all 3 measures (P ≤ .001; Cohen's d range, 0.41 to 0.62). Up to one-fifth of patients with chronic low back pain may be prescribed opioids in a manner that is not adherent to CPGs, thereby placing them at risk for poor outcomes.

Nonopioid Treatments for Chronic Pain—Integrating Multimodal Biopsychosocial Approaches to Pain Management

Jason E. Goldstick, PhD; Gery P. Guy, PhD, MPH; Jan L. Losby, PhD, MSW; Grant T. Baldwin, PhD, MPH; Matthew G. Myers, MPH; Amy S. B. Bohnert, PhD

Association Between Exposure to Complementary and Integrative Therapies and Opioid Analgesic Daily Dose Among Patients on Long-term Opioid Therapy.

To describe the association between exposure to selected complementary and integrative health (CIH) modalities and the trajectory of prescribed opioid analgesic dose within a national cohort of patients receiving long-term opioid therapy (LTOT) in the Veterans Health Administration (VHA). Using national data from VHA electronic health records between October 1, 2017 and September 30, 2019, CIH use was analyzed among 57,437 patients receiving LTOT within 18 VHA facilities serving as evaluation sites of VHA's Whole Health System of Care. Using linear mixed effects modeling controlling for covariates, opioid dose was modeled as a function of time, CIH exposure, and their interaction. Overall, 11.91% of patients on LTOT used any of the focus CIH therapies; 43.25% of those had 4 or more encounters. Patients used acupuncture, chiropractic care, and meditation modalities primarily. CIH use was associated with being female, Black, having a mental health diagnosis, obesity, pain intensity, and baseline morphine-equivalent daily dose. Mean baseline morphine-equivalent daily dose was 40.81 milligrams and dose decreased on average over time. Controlling for covariates, patients with any CIH exposure experienced 38% faster dose tapering, corresponding to a mean difference in 12-month reduction over patients not engaging in CIH of 2.88 milligrams or 7.06% of the mean starting dose. Results support the role of CIH modalities in opioid tapering. The study design precludes inference about the causal effects of CIH on tapering. Analyses did not consider the trend in opioid dose before cohort entry nor the use of other nonopioid treatments for pain. Future research should address these questions and consider tapering-associated adverse events.