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Addiction (Abingdon, England) Dec 2020We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine-naloxone, is delivered in... (Review)
Review
AIMS
We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine-naloxone, is delivered in routine clinical practice, with a focus on factors that affect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally.
METHODS
We completed searches of PubMed, Embase, and grey literature databases for cross-sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted from eligible studies were compared with guidelines provided by WHO.
RESULTS
We found 140 reports from 41 countries that contained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was the most common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadone ranged from 16-131 mg whereas range for buprenorphine was 2.5-19 mg. Access to unsupervised dosing under some conditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several times a week to eight times per year (methadone) or as clinically indicated.
CONCLUSIONS
Opioid agonist treatment practices, including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lower dose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinical benefits.
Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 32289189
DOI: 10.1111/add.15087 -
Journal of the American Association For... Sep 2020Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid...
Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could alleviate pain, but associated adverse effects including gastrointestinal ileus, inappetence, and tissue reactions have been reported. In this study, we compared gross tissue reactions at the site of injection, food consumption, and fecal production after single injections of buprenorphine HCl (Bup; = 7), sustained-release buprenorphine (BupSR; = 8), and high-concentration buprenorphine (BupHC; = 7) during the first 3 d after minor survival surgery. We also measured plasma concentrations of the parent drug, buprenorphine, and 3 metabolites (buprenorphine-3-glucuronide (B3G), norbuprenorphine-3β-glucuronide (N3G), and norbuprenorphine (NB)). Plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for 4 h for Bup and 42 h for BupHC. For BupSR, plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for approximately 77 h, starting 15 h after administration. For all 3 formulations, N3G was the most prominent metabolite in the blood. No injection site reactions were visible grossly in any rabbit. Relative to baseline measures and compared with controls ( = 8), food consumption was suppressed on days 1 through 3 in rabbits that received BupSR and on days 2 through 3 in those given BupHC. Feces production on day 3 was reduced to a greater extent in BupSR rabbits than control animals. Two rabbits in the BupHC group exhibited neurologic signs after drug administration. These adverse effects should be considered when choosing a long-lasting buprenorphine formulation to manage pain in rabbits.
Topics: Analgesics, Opioid; Animals; Animals, Laboratory; Buprenorphine; Delayed-Action Preparations; Male; Pain; Pain Management; Pain Measurement; Rabbits
PubMed: 32674750
DOI: 10.30802/AALAS-JAALAS-19-000132 -
Substance Abuse Treatment, Prevention,... Jul 2022In the United States, access to buprenorphine remains low and disparities regarding who receives treatment have emerged. Federal laws have regulated buprenorphine...
BACKGROUND AND AIMS
In the United States, access to buprenorphine remains low and disparities regarding who receives treatment have emerged. Federal laws have regulated buprenorphine delivery, ultimately limiting its implementation more broadly. At the onset of the COVID-19 pandemic, federal agencies acted quickly to remove a legal barrier, effectively allowing people with opioid used disorder (OUD) to initiate buprenorphine treatment via telemedicine. Leveraging this policy shift, a low barrier buprenorphine treatment initiative via telemedicine was started at syringe service programs in California. We assessed early findings from participants reached by this model of treatment.
METHODS
In May 2020, buprenorphine treatment was offered through a virtual platform to SSP participants in California. SSP staff connected interested participants to virtual appointments with medical providers in a private location. During these visits, clinicians conducted clinical assessments for diagnosing participants with OUD and developed an unsupervised home induction plan for individuals who were eligible. Participants were prescribed a 7-day supply of up to 16 mg daily buprenorphine or 16 mg buprenorphine-2 mg naloxone and asked to return the following week if interested in continuing treatment.
RESULTS
From May 2020 to March 2021, the SSP-buprenorphine virtual care initiative inducted 115 participants onto treatment with 87% of participants inducted on the same day as their referral. Of those inducted, 58% were between the ages of 30 and 49 and 28% were cisgender female. Regarding participants' method of payment to reimburse buprenorphine costs, 92% of participants were covered by Medicare/Medicaid. Overall, 64% of participants returned for a second buprenorphine prescription refill.
CONCLUSIONS
These early findings suggest that this could be a promising approach to improve equity and access to buprenorphine treatment. We encourage policymakers to continue allowing buprenorphine delivery via telemedicine and researchers to study whether this approach improves equity and access to treatment throughout the United States.
Topics: Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Medicare; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; Syringes; Telemedicine; United States; COVID-19 Drug Treatment
PubMed: 35841036
DOI: 10.1186/s13011-022-00483-1 -
JAMA Network Open May 2022As opioid-related deaths continue to climb, methods to reduce barriers to prescribing buprenorphine for individuals with opioid use disorder (OUD) are needed. Recent...
IMPORTANCE
As opioid-related deaths continue to climb, methods to reduce barriers to prescribing buprenorphine for individuals with opioid use disorder (OUD) are needed. Recent conversations by state and federal authorities targeting low-threshold buprenorphine aim to reduce some barriers to prescribing buprenorphine; however, what remains unclear is whether removal of the requirement to obtain a waiver for prescribing buprenorphine through the Drug Addiction Treatment Act of 2000 (an X-waiver) will be enough to increase access to buprenorphine.
OBJECTIVE
To assess barriers and facilitators of obtaining an X-waiver and prescribing buprenorphine.
DESIGN, SETTING, AND PARTICIPANTS
This mixed-method survey study was conducted between September and December 2020; 607 office-based Texas clinicians were surveyed after they attended a buprenorphine X-waiver training course. All attendees between March 2, 2019, and February 28, 2020, were eligible to receive this survey; 126 responses were received (20% response rate: 81 physicians, 37 nurse practitioners, and 8 physician assistants). Data analysis was performed October 2021.
MAIN OUTCOMES AND MEASURES
Surveys measured the extent to which clinicians experienced 9 previously identified barriers during the waiver process and in prescribing buprenorphine. The survey included open-ended items assessing facilitating factors to obtaining a waiver and to prescribing buprenorphine for OUD. The barriers were analyzed using χ2 tests of homogeneity. Qualitative data were analyzed using a constant comparative method.
RESULTS
Among 126 clinicians who responded, 61 (48.4%) had received an X-waiver; of these waivered clinicians, 22 (36%) were prescribing buprenorphine and 39 (64%) were not. "Complexity of X-waiver process," "Perceived lack of professional support and referral network," and "Getting started" were significantly different barriers among waivered and nonwaivered clinicians. Significant differences in barriers experienced between prescribers and nonprescribers were "Getting started" and "Accessing reimbursement for treatment." The most frequently mentioned facilitators involved changes to the waiver training and the need for networks connecting experienced clinicians with those in the initial stages of readiness for prescribing buprenorphine for OUD.
CONCLUSIONS AND RELEVANCE
This survey study's results contribute new understanding of facilitators to obtaining the X-waiver and to prescribing buprenorphine. Furthermore, these findings suggest that to increase access to compassionate evidence-based treatment for OUD, clinicians need ongoing support and mentorship from experienced and knowledgeable clinicians. Interventions aimed at improving access to buprenorphine should focus on facilitating such networks to increase the number of clinicians who obtain an X-waiver and prescribe buprenorphine for OUD.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Physician Assistants
PubMed: 35552721
DOI: 10.1001/jamanetworkopen.2022.12419 -
Psychiatric Services (Washington, D.C.) Jun 2021The authors examined changes in buprenorphine treatment following Medicaid expansion, including the contribution of Medicaid-financed prescriptions.
OBJECTIVE
The authors examined changes in buprenorphine treatment following Medicaid expansion, including the contribution of Medicaid-financed prescriptions.
METHODS
Buprenorphine pharmacy claims for patients were identified in the 2012-2018 IQVIA Longitudinal Prescription Data (LRx) data set, including 79.8% of U.S. retail prescriptions in 2012, increasing to 92.0% in 2018. A cohort analysis was used to assess the mean number of patients in a yearly quarter filling one or more buprenorphine prescriptions during preexpansion (2012-2013) and postexpansion (2014-2018) periods in expansion and nonexpansion states. Interrupted time-series analysis estimated associations of Medicaid expansion period with change in Medicaid-financed treatment. Separate analyses evaluated changes in duration and dose of new treatment episodes focused on mean quarterly number of patients treated with buprenorphine and proportions of new treatment episodes ≥180 days long and with ≥16 mg/day.
RESULTS
Between preexpansion and postexpansion, the mean quarterly number of patients taking buprenorphine increased by 93,300 in expansion states and by 84,960 in nonexpansion states. Corresponding changes for Medicaid-financed patients were 28,760 and 4,050, respectively. The fastest growth in Medicaid-financed treatment occurred among patients ages 25-44. Among new Medicaid-financed treatment episodes, little change was found in the proportion reaching the 180-day threshold, and declines were observed in the proportion receiving ≥16 mg/day.
CONCLUSIONS
The findings are consistent with previous research indicating that Medicaid expansion has increased Medicaid-financed buprenorphine treatment. However, because of offsetting changes in other payment groups, the overall increase in expansion states was similar to the increase in nonexpansion states.
Topics: Adult; Buprenorphine; Cohort Studies; Humans; Medicaid; Patient Protection and Affordable Care Act; Pharmacies; Prescriptions; United States
PubMed: 33730878
DOI: 10.1176/appi.ps.202000491 -
JAMA Network Open Sep 2023In 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that...
IMPORTANCE
In 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear.
OBJECTIVE
To evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023.
INTERVENTIONS
No treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine.
MAIN OUTCOMES AND MEASURES
Mean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).
RESULTS
The simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.
Topics: Adult; Female; Humans; Male; Middle Aged; Buprenorphine; Cost-Benefit Analysis; Opioid-Related Disorders; Patient Acceptance of Health Care; United States
PubMed: 37703018
DOI: 10.1001/jamanetworkopen.2023.29583 -
The Western Journal of Emergency... Jul 2022Emergency departments (ED) are increasingly providing buprenorphine to persons with opioid use disorder. Buprenorphine programs in the ED have strong support from public...
Emergency departments (ED) are increasingly providing buprenorphine to persons with opioid use disorder. Buprenorphine programs in the ED have strong support from public health leaders and emergency medicine specialty societies and have proven to be clinically effective, cost effective, and feasible. Even so, few ED buprenorphine programs currently exist. Given this imbalance between evidence-based practice and current practice, proven behavior change approaches can be used to guide local efforts to expand ED buprenorphine capacity. In this paper, we use the theory of planned behavior to identify and address the 1) clinician factors, 2) institutional factors, and 3) external factors surrounding ED buprenorphine implementation. By doing so, we seek to provide actionable and pragmatic recommendations to increase ED buprenorphine availability across different practice settings.
Topics: Buprenorphine; Emergency Medicine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 35980414
DOI: 10.5811/westjem.2022.2.52978 -
Substance Abuse 2022: Our rural health system sought to (1) increase the number of primary care clinicians waivered to prescribe buprenorphine for treatment of opioid use disorder (OUD) and...
: Our rural health system sought to (1) increase the number of primary care clinicians waivered to prescribe buprenorphine for treatment of opioid use disorder (OUD) and (2) consequently increase the number of our patients receiving this treatment. : We used the Project for Extension for Community Health Outcomes (ECHO) tele-education model as an implementation strategy. We examined the number of clinicians newly waivered, the number of patients treated with buprenorphine, the relationship between clinician engagement with ECHO training and rates of buprenorphine prescribing, and treatment retention at 180 days. : The number of clinicians with a waiver and number of patients treated increased during and after ECHO training. There was a moderate correlation between the number of ECHO sessions attended by a clinician and number of their buprenorphine prescriptions ( = 0.50, = 0.01). The 180-day retention rate was 80.7%. : Project ECHO was highly effective for increasing access to this evidence-based treatment. The high retention rate in this rural context indicates that most patients are increasing their likelihood of favorable outcomes.
Topics: Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Rural Population
PubMed: 34086529
DOI: 10.1080/08897077.2021.1931633 -
The Journal of Pharmacology and... Aug 2021Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the...
Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids, and minimize opioid-cravings while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric effects of opioids of abuse, the extent to which they safely alleviate withdrawal and opioid-cravings corresponds with their intrinsic opioid receptor (MOR) efficacy. In addition to inhibiting the euphoric effects of opioids of abuse, the medium efficacy MOR agonist buprenorphine alleviates withdrawal and opioid-cravings, but its intrinsic MOR efficacy is sufficient such that its utility is limited by abuse and safety liabilities. Although the MOR antagonist naltrexone minimizes euphoria and has no abuse liability, it exacerbates suffering associated with withdrawal and opioid cravings. Therefore, a therapeutic with intrinsic MOR activity between the partial agonist (buprenorphine) and the antagonist (naltrexone) would strike a balance between the benefits and liabilities of these two therapeutics. To address this need, we derived RM1490, an MOR agonist based on a nonmorphinan scaffold that exhibits approximately half the intrinsic MOR efficacy of buprenorphine. In a series of preclinical assays, we compared RM1490 with buprenorphine and naltrexone at doses that achieve therapeutic levels of central nervous system MOR occupancy. RM1490 exhibited a behavioral profile consistent with reduced reward, dependence, and precipitated withdrawal liabilities. RM1490 was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl and did not suppress respiration when combined with diazepam. SIGNIFICANCE STATEMENT: In preclinical studies, RM1490 has a physiological and behavioral profile suitable for opioid use disorder maintenance therapy.
Topics: Buprenorphine; Naltrexone; Opioid-Related Disorders
PubMed: 34011529
DOI: 10.1124/jpet.120.000214 -
The use of buprenorphine in the treatment of drug-resistant depression - an overview of the studies.Psychiatria Polska Apr 2020There is evidence that the endogenous opioid system in the brain plays an important role in mood regulation, and disturbances in its functioning may lead to the... (Review)
Review
There is evidence that the endogenous opioid system in the brain plays an important role in mood regulation, and disturbances in its functioning may lead to the occurrence of depressive disorders. One of the drugs that affect the endogenous opioid system in the CNS is buprenorphine. The article is areview of the studies on the effectiveness of buprenorphine used as an augmentation of antidepressant treatment. The selection of articles was made by browsing the Medline and PubMed databases with the use of key words 'buprenorphine'and 'treatment of drug-resistant depression'. The analysis included thirty one studies. The results indicate that buprenorphine may be effective in drug-resistant depression in a similar manner as other augmentation strategies added to antidepressant treatment. Co-administration of buprenorphine and samidorphan may reduce the risk of addiction without losing the antidepressant effectiveness of buprenorphine. Further methodologically correct studies in this field are needed. In addition to being a partial agonist of the µ receptor, buprenorphine is also a potent antagonist of the kappa type opioid receptors. The antagonism of µ receptors alone does not cause antidepressant effects. Antagonism towards kappa receptors may cause antidepressant effects as well as reduce the severity of anhedonia. Depressed patients who do not respond to standard antidepressant treatment may have dysfunctions of the kappa receptor that are similar to opioid addicts.
Topics: Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Humans
PubMed: 32772054
DOI: 10.12740/PP/102658