Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

Price elasticity of demand for new and recurring opioid prescriptions

Objective: Several U.S. states have recently enacted excise taxes to curb prescription opioid use and other states are considering similar measures. We assessed the effects of increasing out-of-pocket costs (OPC) on new and recurring opioid fills. Methods: We conducted a retrospective cohort study of opioid-naive individuals presenting with acute back pain using data from a nationwide claims repository. We estimated the effect of OPC on the initiation of opioid treatment in logistic regressions, controlling for socio-demographics, medical history, healthcare utilization, insurance type, and region. With the same covariates plus morphine milligram equivalents and days supplied, we estimated the effect of OPC on the number of opioid fills in negative binomial regressions. We report the price elasticity of demand (PED) for prescription opioids, defined as the percentage change in outcome resulting from a two-fold increase in OPC. Results: Of 25,531 adults diagnosed with acute back pain in Q1 of 2018, 2,451 (9.6%) filled at least one opioid prescription. In multivariable regression, the association between OPC and initiating opioid treatment was not significant (PED= -1.9%; 95% CI: -5.5%, 1.7%). However, by region, the PED was -10.3% (95% CI: -18.1%, -2.4%) in the coastal states and 1.6% (95% CI: -2.5%, 5.7%) in the central-southern states. The PED for the number of prescription fills was -3.7% (95% CI: -7.3%, -0.1%), which also differed by region. In the coastal states, the PED was -15.2% (95% CI: -24.7%, -5.7%) and in the central-southern states -1.5% (95% CI: -5.4%, 2.4%). Conclusions: Opioid fills were price sensitive in the coastal states but not in the central-southern states. Policies that would increase OPC might have a restraining effect on opioid consumption in parts, but not all of the U.S.

Opioid reduction for patients with chronic pain in primary care: systematic review

Background: Long-term opioid treatment in patients with chronic pain is often ineffective and possibly harmful. These patients are often managed by general practitioners, who are calling for a clear overview of effective opioid reduction strategies for primary care. Aim: Evaluate effectiveness of opioid reduction strategies applicable in primary care for patients with chronic pain on long-term opioid treatment. Design: Systematic review of controlled trials and cohort studies. Method Literature search conducted in Embase, Medline, Web of Science, Cochrane CENTRAL register of trials, CINAHL, Google Scholar and PsychInfo. Studies evaluating opioid reduction interventions applicable in primary care among adults with long-term opioid treatment for chronic non-cancer pain were included. Risk of bias was assessed using Cochrane risk of bias (RoB) 2.0 tool or Risk-of-Bias in Non-randomized studies of Interventions (ROBINS-I) tool. Narrative synthesis was performed due to clinical heterogeneity in study designs and types of interventions. Results: Five RCTs and five cohort studies were included (total n= 1717, range 35-985) exploring various opioid reduction strategies. Six studies had high RoB, three moderate RoB, and one low RoB. Three cohort studies investigating a GP supervised opioid taper (critical ROBINS-I), an integrative pain treatment (moderate ROBINS-I) and group medical visits (critical ROBINS-I) demonstrated significant between-group opioid reduction. Conclusion: Results carefully point in the direction of a GP supervised tapering and multidisciplinary group therapeutic sessions to reduce long term opioid treatment. However, due to high risk of bias and small sample sizes, no firm conclusions can be made demonstrating need for more high-quality research.

Worse patient-reported outcomes and higher risk of reoperation and adverse events after total hip replacement in patients with opioid use in the year before surgery: a Swedish register-based study on 80,483 patients

Background and purpose — Recent studies indicate that preoperative use of opioids could be associated with higher rates of complications and worse patient-reported outcomes (PROs) after orthopedic surgery. We investigated the prevalence of preoperative opioid use and analyzed its influence on risk of revision, adverse events (AE), and PROs in patients with total hip replacement (THR). Patients and methods — This observational study included 80,483 patients operated on in 2008–2016 with THRs due to osteoarthritis. Data was obtained from the Swedish Hip Arthroplasty Register, Statistics Sweden’s sociodemographic registers, the Swedish National Patient Register, and the Prescribed Drug Register. We focused on patients with ≥ 4 opioid prescriptions filled 1 year prior to THR. To control for confounding, we used propensity scores to weight subjects in our analyses. Logistic and linear regression was used for outcome variables with adjustments for sociodemographic variables and comorbidities. Results — Patients with ≥ 4 opioid prescriptions in the year before THR (n = 14,720 [18%]) had a higher risk of revision within 2 years (1.8% vs. 1.1% OR 1.4, 95% CI 1.3–1.6) and AE within 90 days (9.4% vs. 6.4% OR 1.2, 95% CI 1.2–1.3) compared with patients without opioid treatment in the preoperative period. Patients with ≥ 4 opioid prescriptions rated 5 points worse on a 0–100 scale of Pain VisualAnalogue Scale (VAS) and 9 points worse on a generalhealth (EQ) VAS 1 year postoperatively. Interpretation — Having ≥ 4 opioid prescriptions filled in the year before surgery is associated with a higher risk of revision, adverse events, and worse PROs after THR. Consequently, preoperative opioid treatment should be addressed in the clinical assessment of patients eligible for THR.

Diversity of microglial transcriptional responses during opioid exposure and neuropathic pain

Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Following chronic opioid treatment and peripheral nerve injury (PNI) microglia in the spinal cord display similar morphological responses. Consistent with this observation, functional studies have suggested that microglia activated by PNI or opioids engage common molecular mechanisms to induce hypersensitivity. Here we conducted deep RNA sequencing of acutely isolated spinal cord microglia from male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple OIH and PNI models. Following PNI, we identify a common early proliferative transcriptional event across models that precedes the upregulation of histological markers of activation, followed by a delayed and injury-specific transcriptional response. Strikingly, we found no such transcriptional responses associated with opioid-induced microglial activation, consistent with histological data indicating that microglia number remain stable during morphine treatment. Collectively, these results reveal the diversity of pain-associated microglial transcriptomes and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other CNS pathologies.

Implementation and Outcomes of a Comprehensive Tobacco Free Workplace Program in Opioid Treatment Centers

Tobacco use is exceedingly high among individuals receiving care for opioid addiction, but not commonly addressed by clinicians in treatment settings. Taking Texas Tobacco Free (TTTF) is a comprehensive tobacco-free workplace (TFW) program that builds treatment centers’ capacity to address tobacco use with evidence-based tobacco cessation policies and practices. Here, we examine the process and outcomes of TTTF’s implementation within 7 opioid addiction centers. Program goals were structured according to the RE-AIM framework. Pre- and post-implementation data were collected from client facing and non-client facing employees to assess changes in education, training receipt, knowledge, and intervention behaviors, relative to program goals. Centers reported tobacco screenings conducted and nicotine replacement therapy (NRT) delivered through 6 months post-implementation. Overall, 64.56% of employees participated in TTTF-delivered tobacco education, with a 54.9% gain in tobacco control and treatment knowledge (p < 0.0001), and significant increases in exposure to education about tobacco use and harms among individuals with opioid use disorder (p = 0.0401). There were significant gains in clinicians’ receipt of training in 9/9 tobacco education areas (ps ≤ 0.0118). From pre- to post-implementation, there were mean increases in the use of the 5A’s (ask, advise, assess, assist, and arrange) and other evidence-based interventions for tobacco cessation, with statistically significant gains seen in NRT provision/referral (p < 0.0001). Several program goals were achieved or exceeded; however, 100% center participation in specialized clinical trainings was among notable exceptions. One program withdrew due to competing pandemic concerns; all others implemented comprehensive TFW policies. Overall, TTTF may have improved participating opioid treatment centers’ capacity to address tobacco use, although study limitations, including lower post-implementation evaluation response rates, suggest that results require replication in other opioid addiction treatment settings.

Rural opioid treatment program patient perspectives on take-home methadone policy changes during COVID-19: a qualitative thematic analysis

Background In the United States, methadone for opioid use disorder (OUD) is highly regulated. Federal agencies announced guidelines in March 2020 allowing for relaxation of take-home methadone dispensing at opioid treatment programs (OTPs) to improve treatment access and reduce COVID-19 transmission risk during the public health emergency. We explored patient perspectives at three OTPs serving rural communities on how take-home policy changes were received and implemented and how these changes impacted their addiction treatment and recovery. Methods We completed semi-structured individual qualitative interviews in 2 phases: (1) August–October 2020 and (2) November 2020–January 2021 (total n = 46), anticipating possible policy changes as the pandemic progressed. We interviewed patients with OUD enrolled at 3 rural OTPs in Oregon. Participants received varying take-home methadone allowances following the COVID-19-related policy changes. All interviews were conducted via phone, audio-recorded, and transcribed. We conducted a thematic analysis, iteratively coding transcripts, and deductively and inductively generating codes. Results The 46 participants included 50% women and 89% had Medicaid insurance. Three main themes emerged in the analysis, with no differences between study phases: (1) Adapting to changing OTP policies throughout the pandemic; (2) Recognizing the benefits, and occasional struggles, with increased take-home methadone dosing; and (3) Continuing policies and procedures post-pandemic. Participants described fears and anxieties around ongoing methadone access and safety concerns prior to OTP policy changes, but quickly adapted as protocols soon seemed “natural.” The majority of participants acknowledged significant benefits to increased take-homes independent of reducing COVID-19 infection risk including feeling “more like a normal person,” improved recovery support, reduced time traveling, and having more time with family and for work. Looking to a post-pandemic future, participants thought some COVID-19-related safety protocols should continue that would reduce risk of other infections, make OTP settings less stressful, and result in more individualized care. Conclusions As the pandemic progressed, study participants adapted to rapidly changing OTP policies. Participants noted many unanticipated benefits to increased take-home methadone and other COVID-19 protocols including strengthened self-efficacy and recovery and reduced interpersonal conflict, with limited evidence of diversion. Patient perspectives should inform future policies to better address the ongoing overdose epidemic.