Search Results (14)

Background/Objectives: As long-term prescription opioid use is associated with increased morbidity and mortality, timely dose reduction of prescription opioids should be considered. However, most research has been conducted on patients using heroin. Given the differences between prescription and illicit opioid use, the aim of this review was to provide an overview of pharmacological strategies to reduce prescription opioid use or improve clinical outcomes for people who experience long-term prescription opioid use, including those with opioid use disorder. Methods: We conducted a systematic database search of PubMed, Embase, CINAHL, and the Cochrane Library. Outcomes included dose reduction, treatment dropout, pain, addiction, and outcomes relating to quality of life (depression, functioning, quality of life). Results: We identified thirteen studies (eight randomized controlled trials and five observational studies). Pharmacological strategies were categorized into two categories: (1) deprescribing (tapering) opioids or (2) opioid agonist treatment (OAT) with long-acting opioids. Tapering strategies decreased opioid dosage and had mixed effects on pain and addiction. OAT with buprenorphine or methadone led to improvements in pain relief and quality of life, with a slight (non-significant) preference for methadone in terms of treatment retention (RR = 1.10 [CI: 0.89–1.37]) but not for other outcomes. Most studies had high dropout rates and a serious risk of bias. Conclusions: Tapering reduced prescription opioid doses had mixed effects on pain. OAT improved clinical outcomes without dose reduction. Based on our review findings, there is no clear preference for either tapering or OAT. Tapering may be considered first as it reduces dependency, tolerance, and side effects, but is associated with adverse events and not always feasible. OAT can be a suitable alternative. Non-pharmacological interventions may facilitate tapering. Further research is needed to identify novel pharmacological strategies to facilitate opioid tapering. Registration: PROSPERO 2022 CRD42022323468. Full article

Background/Objectives: The objective of this study was to determine whether preoperative opioid education reduces opioid consumption after spine surgery and which educational methods are the most effective. Orthopedists are the most likely to prescribe opioids among all specialists. To alleviate the prescription opioid crisis, studies have identified ways to taper narcotic dosage and use following surgery. The role of preoperative education and its varying modalities on opioid consumption following spine surgery has yet to be reported in the literature. Methods: The study group received formal education describing the use of opioids, side effects, and alternatives to pain management. Patients were to choose their preferred modality of a 2 min narrated video and two handouts to be watched and read in their individual time, attending a small class led by a physician assistant where they watched the 2 min narrated video along with reading the two handouts or receiving a one-on-one session with the treating spine surgeon. Meanwhile, the control group received standard preoperative education. Refill prescriptions were collected from patients’ electronic medical record charts at the 2-week, 1-month, 3-month, and 6-month postoperative follow-ups. The primary outcome measure was morphine equivalents (MME) of prescription opioids at six months following spine surgery. Results: At 2 weeks postoperatively, there were no statistically significant differences between patients who received any formal narcotic education and those who did not. At 1 and 3 months postoperatively, the video education group (p-value < 0.001), class education group (p-value < 0.001), and the one-on-one education group (p-value < 0.05) all had significant reductions in opioid consumption. At 6 months postoperatively, only the video education group (p-value < 0.001) and the class education group (p-value < 0.01) had significant reductions in opioid consumption. Conclusions: A two-fold approach with a video and handouts significantly decreases the prescription dosage at six months postoperatively and allows for early opioid cessation after undergoing spine surgery. Full article

Opioid use disorder (OUD) is highly prevalent, affecting up to 1% of pregnancies. The current standard of care for the management of OUD during pregnancy has been maintained with opioid agonist treatment (OAT), using either methadone or buprenorphine. OAT use has been associated with a risk of neonatal abstinence syndrome (NAS), which requires a longer neonatal length of stay for monitoring and possible pharmacological treatment. As a result, opioid medical detoxification (OMD) was proposed as an alternative strategy to reduce the stigma associated with OAT and to eliminate the risk of NAS by detoxifying or tapering pregnant persons during their pregnancy before delivery; however, the safety and effectiveness of OMD during pregnancy have not been established. This scoping review aims to summarize recent evidence related to maternal, obstetrical, and neonatal outcomes of OMD in comparison to OAT maintenance. This review also provides recommendations for future research initiatives to fill gaps in managing this patient population. Full article

Siloed pain management across the perioperative period increases the risk of chronic opioid use and impedes postoperative recovery. Transitional perioperative pain services (TPSs) are innovative care models that coordinate multidisciplinary perioperative pain management to mitigate risks of chronic postoperative pain and opioid use. The objective of this study was to examine patients’ experiences with and quality of recovery after participation in a TPS. Qualitative interviews were conducted with 26 patients from The Johns Hopkins Personalized Pain Program (PPP) an average of 33 months after their first PPP visit. A qualitative content analysis of the interview data showed that participants (1) valued pain expectation setting, individualized care, a trusting patient–physician relationship, and shared decision-making; (2) perceived psychiatric treatment of co-occurring depression, anxiety, and maladaptive behaviors as critical to recovery; and (3) successfully sustained opioid tapers and experienced improved functioning after PPP discharge. Areas for improved patient-centered care included increased patient education, specifically about the program, continuity of care with pain specialists while tapering opioids, and addressing the health determinants that impede access to pain care. The positive patient experiences and sustained clinical benefits for high-risk complex surgical patient support further efforts to implement and adapt similar models of perioperative pain care. Full article

While the Food and Drug Administration’s black-box warnings caution against concurrent opioid and benzodiazepine (OPI–BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995–08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21–100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10–20%/weekday followed by 2.5–10%/weekday over three weeks to (2) 10–25%/1–4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2–4 weeks, followed by 2–8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI–BZD, and 4 provided conflicting recommendations on the OPI–BZD deprescribing sequence. Thirty-five states’ websites provided resources for opioid deprescription and three states’ websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI–BZD deprescription. Full article

Buprenorphine is a partial opioid agonist that is Food and Drug Administration (FDA) approved to treat chronic pain and opioid use disorder (OUD). The national prescribing guidelines in the United States (US) recommend that patients transitioning from full opioid agonists to buprenorphine first undergo 12 or more hours of active opioid withdrawal, in order to avoid buprenorphine-precipitated opioid withdrawal. This opioid-free period imposes a significant barrier for many patients. Evidence is accumulating that using microdoses of buprenorphine to cross taper from full-agonist opioids to buprenorphine is a safe and effective way to avoid opioid withdrawal and uncontrolled pain. This microdose cross-tapering strategy is already being used across the US. The US prescribing guidelines and buprenorphine training would benefit from acknowledging this new approach. Additionally, to facilitate this strategy, the FDA should approve transdermal buprenorphine formulations for OUD and manufacturers could produce lower dose formulations of sublingual buprenorphine. The time has come for us to embrace buprenorphine microdosing cross tapers as a new standard of care. Full article

Background: The COVID-19 outbreak disrupted medical access for patients receiving chronic opioid therapy. This study investigated their prescription opioid dosages before and after the 2020 outbreak in Taiwan. Methods: A prospective questionnaire survey was conducted among registered outpatients receiving long-term opioids before July 2019 in Taiwan. The questionnaire included items from the Taiwanese Brief Pain Inventory and quality of life assessment. Follow-up surveys in outpatient departments through October 2020 were conducted to collect opioid prescription data. Results: After a mean of 531 days, the questionnaire responses of 103 of the initial 117 respondents were reviewed. Daily opioid doses decreased for 31 respondents (30.1%), remained roughly equivalent (defined as ±2.5%) for 27 (26.2%), and increased for 45 (43.7%) after the first wave of the pandemic. The use of strong opioids and nonopioid medications did not significantly differ among the three groups, but less fentanyl patch use was noted in the decreased-dose group after the outbreak. More than 70% of the patients received daily high-dose opioids (≥90 morphine milligram equivalents); moreover, 60% reported constipation. No deaths due to opioid overdose occurred during the study period. Conclusions: The COVID-19 outbreak in 2020 did not interrupt access to long-term opioid prescriptions for most registered patients with chronic pain in Taiwan. Less fentanyl patch use was observed in participants whose opioid dose was tapering. Full article

Providing patient-centered care to manage chronic pain and opioid use disorder (OUD) is associated with improved health outcomes. However, adopting a holistic approach to providing care is often challenging in rural communities. This study aims to identify and contrast challenges to providing patient-centered care from the perspective of patients and providers. A participatory design approach was adopted to elicit the perceptions of providers and patients with lived experiences of chronic pain and/or OUD in Jefferson County, Wisconsin. Two focus groups were conducted with each stakeholder group to identify problems that participants face with respect to chronic pain management and OUD and possible solutions. Four interviews were conducted with providers experienced in chronic pain management. Analysis of focus group sessions and interviews show consensus among patients and providers that lack of behavioral health and recovery resources create barriers to effectively manage OUD and chronic pain. However, there was discordance among the two groups about other barriers such as patient and provider attitudes, tapering approach, and access to medications for OUD. This tension among patients and providers can influence patients’ retention in therapy. More efforts are needed to mitigate stigma among providers in rural communities and support psychosocial needs of patients. Full article

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug–gene and drug–drug–gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs). This case describes a 69-year-old female who was referred for PGx testing for uncontrolled chronic pain caused by osteoarthritis and neuropathy. The clinical pharmacist reviewed the PGx test results and medication regimen and identified several (DGIs and DDGIs, respectively) at Cytochrome P450 (CYP) 2C19 and CYP2D6. The recommendations were to: (1) switch tramadol to buprenorphine transdermal patch, an opioid with lower potential for ADEs, to mitigate a CYP2D6 DDGI; (2) gradually discontinue amitriptyline to alleviate the risk of anticholinergic side effects, ADEs, and multiple DDGIs; and (3) optimize the pregabalin. The provider and the patient agreed to implement these recommendations. Upon follow-up one month later, the patient reported an improved quality of life and pain control. Following the amitriptyline taper, the patient experienced tremors in the upper and lower extremities. When the perpetrator drug, omeprazole, was stopped, the metabolic capacity was no longer impeded; the patient experienced possible amitriptyline withdrawal symptoms due to the rapid withdrawal of amitriptyline, which was reinitiated and tapered off more slowly. This case report demonstrates a successful PGx-informed medication safety review that considered drug-induced phenoconversion and mitigated the risks of pharmacotherapy failure, ADEs, and opioid misuse. Full article

Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support. Full article

A multicenter-observational study was performed to assess the effectiveness of rac-methadone, levomethadone, and buprenorphine in opioid-dependent patients in polytherapy in Southern Italy. The primary endpoint was the reduction of urinary positivity to the substances and the maintaining doses. Patients (N = 266, age = 44.80 ± 5.65, male = 79.70%, female = 20.30%) have been recruited. At recruitment, 75% of them were on treatment with rac-methadone, levomethadone, and buprenorphine/naloxone. The patients were grouped into three clusters. The levomethadone patients of Cluster A (N patients = 211), after 180 days, showed stability in urinary methadone positivity, with a marked decrease in heroin −53 ± 4%, cannabinol’s −48 ± 2%, and cocaine −37 ± 6% positivity, with no differences between treatments. A lower QTcF value of 426 ± 8.4 ms was recorded in the levomethadone patients (delta = −19 ms) vs. rac-methadone, at significantly lower doses of levomethadone (−34%, −50.2% in males) (p < 0.05). The Cluster B data were collected from 37 patients, with a high prevalence of comorbidity infections (HIV/HCV/HPV), monitored for 21 months during COVID-19. High doses of levomethadone (58.33 ± 31.58 mg/day) were needed to stabilize those that were negative for opioids and cannabinoids, in contrast to the rac-methadone and buprenorphine/naloxone patients that showed positive toxicology. Eighteen patients of the Cluster C in double diagnosis (major depressive 38.90%, bipolar 27.78%, and schizophrenia 16.67%) were stabilized with high doses of racemate 97.5 ± 8 mg/day, 51.8 ± 5 mg/day of levomethadone (−46.8% vs. rac-methadone; −71% in men), and 2.5 ± 1 mg/day of buprenorphine/naloxone. Three patients in remission were treated with tapering doses of levomethadone. Significantly reduced QTcF values were recorded with levomethadone (delta −32 ms vs. rac-methadone) in the bipolar patients, as well as the schizophrenia patients in remission (delta −45.19 ms vs. rac-methadone). Our patients were safely stabilized. Levomethadone, compared to the racemate, contributes to reducing the illicit use, especially of opioids and cannabinoids at significantly lower doses with cardiovascular safety, which, in bipolar patients, is clinically significant. Full article

Alzheimer’s disease and related dementias (ADRD), pain and chronic complex conditions (CCC) often co-occur leading to polypharmacy and with potential inappropriate medications (PIMs) use, are important risk factors for adverse drug reactions and hospitalizations in older adults. Many US veterans are at high risk for persistent pain due to age, injury or medical illness. Concerns about inadequate treatment of pain—accompanied by evidence about the analgesic efficacy of opioids—has led to an increase in the use of opioid medications to treat chronic pain in the Veterans Health Administration (VHA) and other healthcare systems. This study aims to investigate the relationship between receipt of pain medications and centrally (CNS) acting PIMs among veterans diagnosed with dementia, pain intensity, and CCC 90-days prior to hospitalization. The final analytic sample included 96,224 (81.7%) eligible older veterans from outpatient visits between October 2012–30 September 2013. We hypothesized that veterans with ADRD, and severe pain intensity may receive inappropriate pain management and CNS-acting PIMs. Seventy percent of the veterans, and especially people with ADRD, reported severe pain intensity. One in three veterans with ADRD and severe pain intensity have an increased likelihood for CNS-acting PIMs, and/or opioids. Regular assessment and re-assessment of pain among older persons with CCC, patient-centered tapering or discontinuation of opioids, alternatives to CNS-acting PIMs, and use of non-pharmacological approaches should be considered. Full article

We describe the case of a 75-year-old female with chronic low back pain (CLBP), on opioids for more than 15 years. She presented with an acute episode of nausea, vomiting, abdominal pain, and shortness of breath. After a complete work-up, it was concluded that her presenting symptoms were likely due to her high levels of CLBP and high dose opioids. At the time of intervention, her opioid dosage was between 50–90 MME (Morphine milligram equivalent) (Norco 8 × 7.5 mg/day + Fentanyl 12 mcg patch). She was subsequently seen by the physician for seven outpatient internal medicine appointments over nine months and received Pain Neuroscience Education (PNE) in conjunction with monitored tapering of opioids and other medication associated with her CLBP. This case report demonstrates how a physician might deliver PNE as a viable nonpharmacological treatment option for the tapering of long-term opioids for chronic pain. Full article

Naltrexone and naloxone are classical opioid antagonists. In substantially lower than standard doses, they exert different pharmacodynamics. Low-dose naltrexone (LDN), considered in a daily dose of 1 to 5 mg, has been shown to reduce glial inflammatory response by modulating Toll-like receptor 4 signaling in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade. Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn’s disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer. In a dosing range at less than 1 μg per day, oral naltrexone or intravenous naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling. This dose is termed ultra low-dose naltrexone/naloxone (ULDN). It has been of use in postoperative control of analgesia by reducing the need for the total amount of opioids following surgery, as well as ameliorating certain side-effects of opioid-related treatment. A dosing range between 1 μg and 1 mg comprises very low-dose naltrexone (VLDN), which has primarily been used as an experimental adjunct treatment for boosting tolerability of opioid-weaning methadone taper. In general, all of the low-dose features regarding naltrexone and naloxone have been only recently and still scarcely scientifically evaluated. This review aims to present an overview of the current knowledge on these topics and summarize the key findings published in peer-review sources. The existing potential of LDN, VLDN, and ULDN for various areas of biomedicine has still not been thoroughly and comprehensively addressed. Full article