Buprenorphine-naloxone Research Articles

The role of Alberta pharmacists working in opioid use disorder and their potential to prescribe buprenorphine-naloxone: A qualitative study.

Opioid toxicity continues to have significant morbidity and mortality in Alberta. Opioid agonist therapy is an effective treatment for opiate use disorder (OUD), with first-line treatment with buprenorphine-naloxone (BUP-NAL) being both highly effective and safe. Barriers to care limit access to treatment, and more access points for treatment are needed. Pharmacists in Alberta have a wide scope of prescribing authority and high accessibility. This study describes the barriers to care and the roles of pharmacists engaged in OUD treatment, and explores the potential for pharmacists to prescribe BUP-NAL to improve access to care. Semistructured interviews were conducted with pharmacists from Alberta in January 2024. Key informants were identified using professional networks and the reverse snowball method, and continued until data saturation. Thematic analysis was conducted by 2 investigators using open coding. Ten pharmacists were interviewed, and 4 major themes emerged: barriers to access OUD treatment, the current role of pharmacists in caring for patients with OUD, the future role of pharmacists as prescribers of BUP-NAL, and enabling pharmacists to prescribe. Patients experience many barriers to care, and a complex health system contributes to this. Pharmacists working with patients with OUD are highly knowledgeable and involved in assessing, managing, and monitoring therapy in a multidisciplinary capacity. Extending authority for pharmacists to prescribe BUP-NAL can improve access to care but must consider collaboration and social context. Pharmacists are skilled and positioned to improve access to care for patients with OUD needing BUP-NAL.

Efficacy of Screening and Brief Intervention for Alcohol Misuse in Opioid Agonist Maintenance Treatment: A Randomized Clinical Trial

ABSTRACT Alcohol misuse is common in persons on opioid agonist maintenance treatment (OAMT). We tested the efficacy of screening and brief intervention (SBI) for harmful/hazardous alcohol use in buprenorphine/naloxone (BNX)-assisted OAMT. It was a double-blind, parallel-group, randomized trial, where 150 participants with alcohol misuse (Alcohol Use Disorder Identification Test – AUDIT 8–19) on BNX were allocated equally to receive either a single session SBI or screening and brief advice (control). Participants were followed up at three months. The primary outcome was the change in AUDIT; other outcomes were risk transition, change in the frequency of heavy drinking, days of abstinence from alcohol, Gamma-glutamyl transferase (GGT) levels, non-prescription opioid use, and adherence to BNX. Follow-up data was gathered from 138 participants. SBI participants had a higher reduction in AUDIT scores at the follow-up (F = 129. 173, df = 1, p < .001, ηp 2 =.469). A higher proportion of participants transitioned to a low-risk category in the SBI group. The SBI group showed a higher reduction in heavy drinking and days of alcohol abstinence. Although the proportion of persons with normal serum GGT increased in both groups, the difference was not significant at the follow-up. The SBI group performed better in non-prescription opioid use and BNX adherence.

Implementation of a rural emergency department-initiated buprenorphine program in the mountain west: a study protocol

BackgroundOpioid related overdose morbidity and mortality continue to significantly impact rural communities. Nationwide, emergency departments (EDs) have seen an increase in opioid use disorder (OUD)-related visits compared to other substance use disorders (SUD). ED-initiated buprenorphine is associated with increased treatment engagement at 30 days. However, few studies assess rural ED-initiated buprenorphine implementation, which has unique implementation barriers. This protocol outlines the rationale and methods of a rural ED-initiated buprenorphine program implementation study.MethodsThis is a two-year longitudinal implementation design with repeated qualitative and quantitative measures of an ED-initiated buprenorphine program in the rural Mountain West. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework outlines intervention assessments. The primary outcome is implementation measured by ED-initiated buprenorphine protocol core components. Reach, adoption, and maintenance are secondary outcomes. External facilitators from an academic institution with addiction medicine and prior program implementation expertise partnered with community hospital internal facilitators to form an implementation team. External facilitators provide ongoing support, recommendations, education, and academic detailing. The implementation team designed and implemented the rural ED-initiated buprenorphine program. The program includes OUD screening, low-threshold buprenorphine initiation, naloxone distribution and administration training, and patient navigator incorporation to provide warm hand off referrals for outpatient OUD management. To address rural based implementation barriers, we organized implementation strategies based on Expert Recommendations for Implementing Change (ERIC). Implementation strategies include ED workflow redesign, local needs assessments, ED staff education, hospital leadership and clinical champion involvement, as well as patient and community resources engagement.DiscussionMost ED-initiated buprenorphine implementation studies have been conducted in urban settings, with few involving rural areas and none have been done in the rural Mountain West. Rural EDs face unique barriers, but tailored implementation strategies with external facilitation support may help address these. This protocol could help identify effective rural ED-initiated buprenorphine implementation strategies to integrate more accessible OUD treatment within rural communities to prevent further morbidity and mortality.Trial RegistrationClinicalTrials.gov National Clinical Trials, NCT06087991. Registered 11 October 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06087991.

In treating opioid use disorder, does buprenorphine have an increased rate of misuse and diversion compared with buprenorphine–naloxone?

In treating opioid use disorder, does buprenorphine have an increased rate of misuse and diversion compared with buprenorphine–naloxone?

Learning Optimal Dynamic Treatment Regimes from Longitudinal Data.

Studies often report estimates of the average treatment effect (ATE). While the ATE summarizes the effect of a treatment on average, it does not provide any information about the effect of treatment within any individual. A treatment strategy that uses an individual's information to tailor treatment to maximize benefit is known as an optimal dynamic treatment rule (ODTR). Treatment, however, is typically not limited to a single point in time; consequently, learning an optimal rule for a time-varying treatment may involve not just learning the extent to which the comparative treatments' benefits vary across the characteristics of individuals, but also learning the extent to which the comparative treatments' benefits vary as relevant circumstances evolve within an individual. The goal of this paper is to provide a tutorial for estimating ODTR from longitudinal observational and clinical trial data for applied researchers. We describe an approach that uses a doubly-robust unbiased transformation of the conditional average treatment effect. We then learn a time-varying ODTR for when to increase buprenorphine-naloxone (BUP-NX) dose to minimize return-to-regular-opioid-use among patients with opioid use disorder. Our analysis highlights the utility of ODTRs in the context of sequential decision making: the learned ODTR outperforms a clinically defined strategy.

Trends of Buprenorphine Prescribing for Opioid Dependence Before, and During the Early and Later Part of the COVID-19: A Study from a Large Publicly-Funded Opioid Agonist Treatment Services in India.

The COVID-19 pandemic has affected the availability and access to medications for opioid dependence (OD). We examined the monthly trends in new buprenorphine/naloxone (BNX) treatment episodes, number of clinical visits for BNX, BNX dispensed per person, and BNX prescription over 56-month, which included pre-pandemic, during early, and later part of pandemic (Jan 2017 - Aug 2022). Research data were collected from the pharmacy database of a large publicly funded treatment center in India. A flexible, low-threshold service was adopted in April 2020 in response to the lockdown implemented on 25 March 2020. Change Point analyses were performed to examine monthly trends visually and statistically. We used Autoregressive integrated moving averages to forecast trends from April to Aug 2020 and March to August 2022, using Jan 2017 to March 2020 and March 2020 to February 2022 as training datasets. 993 patients were started on BNX treatment, 40452 BNX clinic attendances were made, 1401393 BNX tablets were dispensed, and 6795 new patients with OD were registered. The observed data for clinic attendance for BNX was significantly lower than the projected estimates in April -Aug 2020; however, observed new treatment episodes and monthly BNX prescriptions were within the 95% projected estimates; BNX dispensed per person was significantly more than the projected estimate. In contrast, observed BNX prescription trends surpassed the upper limit of 95% CI in March-Aug 2022. A low-threshold and flexible treatment service could mitigate the unintended consequences of pandemic-induced restrictions.

Neurocognitive Functions After 6-Month Buprenorphine (Naloxone)-Based Opioid Agonist Maintenance Treatment: A Controlled Prospective Study.

Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.

Factors associated with frequent buprenorphine / naloxone initiation in a national survey of Canadian emergency physicians.

To identify individual and site-related factors associated with frequent emergency department (ED) buprenorphine/naloxone (BUP) initiation. BUP initiation, an effective opioid use disorder (OUD) intervention, varies widely across Canadian EDs. We surveyed emergency physicians in 6 Canadian provinces from 2018 to 2019 using bilingual paper and web-based questionnaires. Survey domains included BUP-related practice, demographics, attitudes toward BUP, and site characteristics. We defined frequent BUP initiation (the primary outcome) as at least once per month, high OUD prevalence as at least one OUD patient per shift, and high OUD resources as at least 3 out of the following 5 resources: BUP initiation pathways, BUP in ED, peer navigators, accessible addiction specialists, and accessible follow-up clinics. We excluded responses from sites with <50% participation (to minimize non-responder bias) and those missing the primary outcome. We used univariate analysis to identify associations between frequent BUP initiation and factors of interest, stratifying by OUD prevalence. We excluded 3 responses for missing BUP initiation frequency and 9 for low response rate at one ED. Of the remaining 649 respondents from 34 EDs, 374 (58%) practiced in metropolitan areas, 384 (59%) reported high OUD prevalence, 312 (48%) had high OUD resources, and 161 (25%) initiated BUP frequently. Age, gender, board certification and years in practice were not associated with frequent BUP initiation. Site-specific factors were associated with frequent BUP initiation (high OUD resources [OR 6.91], high OUD prevalence [OR 4.45], and metropolitan location [OR 2.39],) as were individual attitudinal factors (willingness, confidence, and responsibility to initiate BUP.) Similar associations persisted in the high OUD prevalence subgroup. Individual attitudinal and site-specific factors were associated with frequent BUP initiation. Training to increase physician confidence and increasing OUD resources could increase BUP initiation and benefit ED patients with OUD.

Cost-effectiveness of full and partial opioid agonists for opioid use disorder in outpatient settings: United States healthcare sector perspective

IntroductionStudies show that medications for opioid use disorder (MOUD) reduce illicit opioid use, emergency healthcare services, opioid-related overdose, and death. However, few studies have investigated the long-term cost-effectiveness of MOUD in office-based opioid treatment (OBOT) and opioid treatment program (OTP) settings. We aimed to estimate the cost, utility, quality-adjusted life years gained (QALYs), and incremental cost-effectiveness ratios (ICERs) of three MOUD compared to each other and counseling without medication from a US healthcare sector perspective. MethodsOur study developed a Markov model to conduct a cost-effectiveness analysis of counseling and three MOUD in the OBOT and OTP settings: sublingual buprenorphine/naloxone (BUPNX), buprenorphine extended-release (XR-BUP) injection, and oral methadone. The model included five health states representing combinations of receiving or off treatment while either using or not actively using illicit opioids, and death. The cycle length was one month; the time-horizon was ten years. The study obtained model inputs from systematic reviews of published literature and public data. A 3 % annual discount rate was applied to cost and utility calculation. The primary outcomes included total costs, life-years (LYs), QALYs, and ICERs. We also conducted a scenario analysis using a hypothetical OBOT outpatient setting with methadone. ResultsIn the base-case OBOT setting, the total costs and QALYs, respectively, were counseling $22,848, 5.60; BUPNX $29,875, 5.82; and XR-BUP $63,936, 5.87. ICERs were $32,345/QALY (BUPNX vs. counseling) and $625,858/QALY (XR-BUP vs BUPNX). In the OTP setting, the total costs of counseling, methadone, BUPNX, and XR-BUP were $20,124, $27,000, $33,500, and $75,272, respectively. QALYs of methadone were 5.86. QALYs of counseling, BUPNX, and XR-BUP remained the same as in the OBOT setting. Incremental ICERs were $26,714/QALY (methadone vs counseling) and $3,337,623/QALY (XR-BUP vs methadone). BUPNX was dominated by methadone. In the scenario analysis, BUPNX was also dominated by methadone. ConclusionsOutpatient MOUD resulted in important gains in quality of life and life expectancy. In both OBOT and OTP settings, XR-BUP was not cost-effective. BUPNX was cost-effective in the OBOT setting, while it was dominated by methadone in the OTP setting. The cost-effectiveness of BUPNX and XR-BUP could be enhanced if the costs of these medications were reduced.

EE504 Buprenorphine–Naloxone Film Yields Cost Savings in Administration Time Compared With Sublingual Tablets in Sweden

EE504 Buprenorphine–Naloxone Film Yields Cost Savings in Administration Time Compared With Sublingual Tablets in Sweden

Buprenorphine-Naloxone Film Versus Tablets for Opioid Use Disorder

What Is the Issue?&#x0D; &#x0D; Medication for opioid use disorder is essential for reducing cravings, withdrawal symptoms, and facilitating recovery, with buprenorphine being preferred over methadone by health care providers and people with opioid use disorder due to its lower overdose risk and perceived lower side effect profile.&#x0D; In Canada, buprenorphine is available in various formulations, including buprenorphine-naloxone (BUP-NAL), commonly chosen for its safety benefits and convenience.&#x0D; Sublingual buprenorphine-naloxone films offer faster dissolution and potentially other benefits compared to sublingual tablets, evaluating their comparative clinical and cost-effectiveness is important as they become more widely available.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; To inform decisions about the appropriate selection of BUP-NAL formulations for treating individuals with opioid use disorder, CADTH sought to identify and summarize literature comparing the clinical effectiveness and cost-effectiveness of sublingual BUP-NAL films versus tablets. We also attempted to identify evidence-based recommendations for the use of BUP-NAL film.&#x0D; A research information specialist conducted a literature search of the peer-reviewed and grey literature with a search strategy focused on sublingual BUP-NAL. The search was limited to English-language documents published since January 1, 2018. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included study, and narratively summarized the findings.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; Sublingual BUP-NAL films may have lower abuse rates compared to sublingual BUP-NAL tablets among people who seek treatment at substance abuse treatment centres or who present needing medical advice or treatment for intentional misuse or abuse of potentially toxic substances, including opioids (1 study).&#x0D; We did not find any clinical effectiveness studies that assessed aspects related to drug ingestion, drug abuse cessation, treatment programs, health-related quality of life, mental health or safety of BUP-NAL films or tablets that met our criteria for this review.&#x0D; We did not find any studies on cost-effectiveness or evidence-based guidelines of sublingual BUP-NAL films or tablets that met our criteria for this review.&#x0D; &#x0D; What Does It Mean?&#x0D; &#x0D; Limited evidence from this review suggests that sublingual BUP-NAL films may lead to lower substance abuse rates compared to sublingual BUP-NAL tablets among people with OUD; however, we require more comprehensive research with rigorous methodological approaches to understand this topic better.&#x0D; Considering the low abuse potential for BUP-NAL film, decision-makers may wish to use this formulation in settings where the potential for substance abuse is high.&#x0D;

Risk of relapse to non-opioid addictive substances among opioid dependent patients treated with an opioid receptor antagonist or a partial agonist: A randomized clinical trial

Background and objectiveFirst study to assess any compensatory increase in use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended-release naltrexone. MethodA multicenter, outpatient, open-label randomized clinical trial where patients received intramuscular extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8–24/2–6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week follow-up. The study was conducted at five urban addiction clinics and detoxification units in Norway between November 2012, and July 2016. ResultsAmong the 143 patients, 106 men and 37 women, there were no significant differences between those randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68–2.53), amphetamines (HR 0.88; 0.43–1.80), benzodiazepines (HR 1.24; 0.74–2.09) or cannabis (HR 1.55; 0.83–2.89). Also in the 36-week (12–48 weeks) follow-up period we found no significant differences between patients continuing with XR-NTX compared to those switching to XR-NTX after the randomized period in risk of first relapse to any non-opioid substance. In both study periods, the mean time in the study were longer among those relapsing to non-opioid addictive substances than those who did not. There was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances. ConclusionThere was no increase in the risk of relapse to non-opioid addictive substances neither in short term nor longer-term treatment with extended-release naltrexone.Trial registrationclinicaltrials.gov Identifier: NCT01717963

The Association Between Self-Reported Anxiety and Retention in Opioid Agonist Therapy: Findings From a Canadian Pragmatic Trial.

Prescription-type opioid use disorder (POUD) is often accompanied by comorbid anxiety, yet the impact of anxiety on retention in opioid agonist therapy (OAT) is unclear. Therefore, this study investigated whether baseline anxiety severity affects retention in OAT and whether this effect differs by OAT type (methadone maintenance therapy (MMT) vs. buprenorphine/naloxone (BNX)). This secondary analysis used data from a pan-Canadian randomized trial comparing flexible take-home dosing BNX and standard supervised MMT for 24 weeks. The study included 268 adults with POUD. Baseline anxiety was assessed using the Beck Anxiety Inventory (BAI), with BAI ≥ 16 indicating moderate-to-severe anxiety. The primary outcomes were retention in assigned and any OAT at week 24. In addition, the impact of anxiety severity on retention was examined, and assigned OAT was considered an effect modifier. Of the participants, 176 (65%) reported moderate-to-severe baseline anxiety. In adjusted analyses, there was no significant difference in retention between those with BAI ≥ 16 and those with BAI < 16 assigned (29% vs. 28%; odds ratio (OR) = 2.03, 95% confidence interval (CI) = 0.94-4.40; P = 0.07) or any OAT (35% vs. 34%; OR = 1.57, 95% CI = 0.77-3.21; P = 0.21). In addition, there was no significant effect modification by OAT type for retention in assigned (P = 0.41) or any OAT (P = 0.71). In adjusted analyses, greater retention in treatment was associated with BNX (vs. MMT), male gender identity (vs. female, transgender, or other), enrolment in the Quebec study site (vs. other sites), and absence of a positive urine drug screen for stimulants at baseline. Baseline anxiety severity did not significantly impact retention in OAT for adults with POUD, and there was no significant effect modification by OAT type. However, the overall retention rates were low, highlighting the need to develop new strategies to minimize the risk of attrition from treatment. This study was registered in ClinicalTrials.gov (NCT03033732).

Utilization of Opioid Agonist Therapies in Canada

&#x0D; Canada continues to experience an opioid crisis that has had a devastating impact on public health, highlighting the importance of management strategies for opioid use disorder (OUD). Several opioid agonist therapies (OATs) for the management of OUD are available in Canada, including recent approvals of new brand name drugs and generic versions of widely used OATs.&#x0D; Coverage criteria for OATs are comparable across public drug plans in Canada. Methadone hydrochloride (HCL) and the combination of buprenorphine HCL and naloxone HCL (buprenorphine HCL-naloxone HCL) are typically listed as regular or open benefits; generics for these 2 medications have been available since 2020 and 2013, respectively. Sublocade and Probuphine — long-acting buprenorphine preparations approved by Health Canada in 2018 — have varied coverage that is often dependent on prior therapy requirement.&#x0D; The annual number of public claims for OATs decreased by 19.5% from 2018 to 2022. The market share of claims during this period was dominated by methadone HCL and buprenorphine HCL-naloxone HCL, with an increase in claims market share for buprenorphine over time (starting in 2020) and a negligible contribution by buprenorphine HCL. Additionally, in a subanalysis on the number of OAT claimants, the results did not indicate a decrease in individual beneficiaries for these medications; therefore, the decrease in OAT claims was likely driven by increased usage of OATs that require fewer claims per patient, as opposed to decreased OAT use in the population.&#x0D; Despite the decrease in annual OAT claims during the analysis period, total OAT expenditures increased every year, with a 67.0% increase from 2018 to 2022 (5-year total of $307 million). The increase was initially driven by buprenorphine HCL-naloxone HCL, which increased from $27 million (58.9% of OAT expenditures) in 2018 to $39 million (67.2% of OAT expenditures) in 2019. Thereafter, expenditures for buprenorphine drove overall OAT cost increases from 2020 onward, accounting for $22 million (28.2% of OAT expenditures) in 2022. In contrast, methadone HCL accounted for a decreasing proportion of expenditures each year ($19 million or 41.1% of OAT expenditures in 2018 to $16 million or 21.0% of OAT expenditures in 2022), despite having the greatest proportion of claims throughout the study period.&#x0D; The availability of new OAT formulations and generic versions of existing products, as well as other notable regulatory policy changes (e.g., Health Canada’s removal of the need for an exemption to prescribe methadone HCL) and reimbursement decisions (e.g., positive reimbursement recommendations from CADTH for the newer branded OATs, Sublocade and Probuphine), impacted the observed utilization and expenditure patterns, and will likely continue to influence decision-making, particularly where coverage has recently changed or has yet to change to reflect the evolving landscape. If the utilization of injectable buprenorphine (Sublocade) continues at the rate observed in this analysis, it will likely continue to drive increases in OAT expenditures; Sublocade has several patents and the earliest patent expiry is not until 2031, so generic versions of this formulation will likely not be available for several more years. Overall, the findings of this analysis may help to inform jurisdictions in funding decisions regarding OATs for the treatment of OUD.&#x0D;

Effectiveness of buprenorphine (naloxone) for opioid dependence does not differ across opioid categories: a retrospective cohort study from India

ABSTRACT We aimed to examine whether treatment retention, abstinence, and adherence to buprenorphine-naloxone (BNX) differ among individuals with opioid dependence (OD) across three common categories of opioids- heroin, opium, and low-potency pharmaceutical. In a retrospective cohort study, we analyzed outpatient treatment records from March 2020 through February 2022. Opioid category was determined by lifetime and current opioid use. We defined treatment retention as weeks of uninterrupted clinic attendance. Abstinence and BNX adherence were calculated by weeks of extra-medical opioid-negative and buprenorphine-positive urine screening from treatment initiation. Four-hundred-thirteen patients were eligible; 406 (98.3%) were included in the final analysis. Two-hundred-ninety (71.4%) patients were dependent on heroin; 66 (16.3%) were natural opioid dependent, and 50 (12.3%) were dependent on low-potency pharmaceutical opioids. BNX effectiveness in treatment retention, abstinence, and adherence did not differ in patients dependent on heroin, natural, and low-potency pharmaceutical opioids. Patients on ≥8 mg daily BNX had better retention and adherence than those on <8 mg daily. Patients from lower socioeconomic status (SES) had higher odds of retention, abstinence, and adherence than those from upper/middle SES. Treatment outcomes on BNX did not differ across opioid categories. However, BNX should be dosed adequately.

The toll of opioid dependence: A research report on the possible role of Toll-like receptor-4 and related immune markers in opioid dependence.

The opioid receptors in the central nervous system and immune system contribute to its reinforcing effect. Xenobiotics-associated molecular pattern of opioids interacts with Toll-like receptor-4 (TLR-4) on the glial cell surface and increases dopaminergic activity in the nucleus accumbens in preclinical studies. We wanted to examine whether treatment with buprenorphine-naloxone (BNX) might be associated with changes in immunological markers in individuals with opioid dependence (OD). We recruited 30 individuals with OD on buprenorphine and 30 age- and sex-matched healthy controls (HCs). We measured the neutrophil (N), lymphocyte (L), CD-4, and CD-8 T-cell count and estimated plasma TLR-4 level in the HC group once. We measured the immunological markers, craving, pain, and perceived stress in the OD group at the treatment initiation (baseline) and after 4 weeks (±2 weeks) of treatment with BNX. The mean severity score on the OD questionnaire was 72.8 (SD 5.4). At baseline, OD had a higher N: L ratio and lower lymphocyte percentage than HC. Plasma TLR-4 concentration increased significantly after 1 month of treatment (t = -3.09, P = 0.004). Craving, pain, and perceived stress correlated with absolute neutrophil count, N: L ratio, and CD-8 T-cell count, although lost significance after corrections for multiple comparisons. The increase in TLR-4 after treatment with BNX may indicate the rescue from nonprescription opioid-induced immunosuppression or the introduction of a novel xenobiotics-associated molecular pattern of BNX.

Cost-effectiveness of flexible take-home buprenorphine-naloxone versus methadone for treatment of prescription-type opioid use disorder

BackgroundOur objective was to examine the cost-effectiveness of flexible take-home buprenorphine-naloxone (BNX) versus methadone alongside the OPTIMA trial in Canada. MethodsThe OPTIMA study was a pragmatic, open-label, noninferiority, two-arm randomized controlled trial, to assess the comparative effectiveness of flexible take-home BNX vs. methadone in routine clinical care for individuals with prescription-type opioid use disorder. We evaluated cost-effectiveness using a semi-Markov cohort model. Probabilities of overdose were calibrated, accounting for fentanyl prevalence and other overdose risk factors such as naloxone availability. We considered health sector and societal cost perspectives, including costs (2020 CAD) for treatment, health resource use, criminal activity, and health state-specific preference weights as outcomes to calculate incremental cost-effectiveness ratios. Six-month and lifetime (3% annual discount rate) time-horizons were explored. ResultsOver a lifetime time horizon, individuals accumulated −0.144 [CI: −0.302, −0.025] incremental quality-adjusted life years (QALYs) in BNX compared with methadone. Incremental costs were -$2047 [CI: -$39,197, $24,250] from a societal perspective, and -$4549 [CI: -$6332, -$3001] from a health sector perspective. Over a six-month time-horizon, individuals accumulated 0.002 [credible interval (CI): −0.011, 0.016] incremental QALYs in BNX compared with methadone. Incremental costs were -$307 [CI: -$10,385, $8466] from a societal perspective and -$1111 [CI: -$1517, -$631] from a health sector perspective. BNX was dominated (costlier, less effective) in 49.7% of simulations when adopting a societal perspective over a lifetime time horizon. ConclusionsFlexible take-home BNX was not cost-effective versus methadone over a lifetime time horizon, resulting from better treatment retention in methadone compared to BNX.

Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study

IntroductionConflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone. MethodsWe analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6. ResultsThe mean maximum dose taken during the study was 17.3 mg/day (range = 0.5–32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10–170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = −0.06 ± 0.04; p = 0.15), craving (aβ ± SE = −0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3). ConclusionsThe current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Real World Outcomes in Uninsured Patients with Opioid Use Disorder Transitioning from Inpatient to Outpatient Treatment

By George C. Coleman, Joseph B. Williams & 3 more. A retrospective chart review of 47 patients with OUD initiating either buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX) showed higher rates of retention in outpatient treatment for those treated with BUP-NX.

Enumerating contributions of fentanyls and other factors to the unprecedented 2020 rise in opioid overdose deaths: model-based analysis.

In 2020, the ongoing US opioid overdose crisis collided with the emerging COVID-19 pandemic. Opioid overdose deaths (OODs) rose an unprecedented 38%, due to a combination of COVID-19 disrupting services essential to people who use drugs, continued increases in fentanyls in the illicit drug supply, and other factors. How much did these factors contribute to increased OODs? We used a validated simulation model of the opioid overdose crisis, SOURCE, to estimate excess OODs in 2020 and the distribution of that excess attributable to various factors. Factors affecting OODs that could have been disrupted by COVID-19, and for which data were available, included opioid prescribing, naloxone distribution, and receipt of medications for opioid use disorder. We also accounted for fentanyls' presence in the heroin supply. We estimated a total of 18,276 potential excess OODs, including 1,792 lives saved due to increases in buprenorphine receipt and naloxone distribution and decreases in opioid prescribing. Critically, growth in fentanyls drove 43% (7,879) of the excess OODs. A further 8% is attributable to first-ever declines in methadone maintenance treatment and extended-released injectable naltrexone treatment, most likely due to COVID-19-related disruptions. In all, 49% of potential excess OODs remain unexplained, at least some of which are likely due to additional COVID-19-related disruptions. While the confluence of various COVID-19-related factors could have been responsible for more than half of excess OODs, fentanyls continued to play a singular role in excess OODs, highlighting the urgency of mitigating their effects on overdoses.