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Background: Buprenorphine may provide superior analgesia to full opioid agonist therapy and reverse the effects of opioid-induced hyperalgesia, while having a favorable safety profile and fewer adverse effects, in chronic non-cancer pain treatment. Low-dose initiation of buprenorphine is a useful strategy for patients on long-term opioid therapy because it avoids the need for moderate opioid withdrawal required for traditional buprenorphine initiations. However, there are few published reports of low-dose initiation regimens in the setting of chronic pain. Aims: The aim of the study was to describe a case series of individuals living with chronic pain who were transitioned from long-term full opioid agonist therapy onto sublingual buprenorphine/naloxone using low-dose initiation regimens. Methods: This study is a retrospective case series that included all patients who received care at an outpatient chronic pain clinic and were scheduled for low-dose initiation of buprenorphine/naloxone between March 2020 and December 2022. Data were collected through a retrospective review of electronic medical records and results were analyzed using descriptive statistics. Results: Eighteen patients underwent transitions from their baseline opioids onto buprenorphine/naloxone using a low-dose initiation regimen. Of those patients, 17 successfully completed the initiation (94.44%), 12 experienced adverse effects during the initiation (66.67%), with only one patient requiring treatment discontinuation, and all adverse effects resolved once maintenance doses of buprenorphine/naloxone were established. The mean Clinical Global Impression-Improvement score after initiation was 2 (1-5). Conclusion: Low-dose initiation is an effective approach to transition patients with chronic non-cancer pain from long-term opioid therapy to buprenorphine/naloxone without major complications or worsening pain.
Contexte: La buprénorphine peut offrir une analgésie supérieure à celle d'un traitement par agonistes opioïdes complet et inverser les effets de l'hyperalgésie induite par les opioïdes, tout en présentant un profil d'innocuité favorable et moins d'effets indésirables dans le traitement de la douleur chronique non cancéreuse. L'initiation à faible dose de la buprénorphine est une stratégie utile pour les patients sous traitement opioïde à long terme, car elle évite le besoin de sevrage des opioïdes modéré nécessaire pour les traitements traditionnels à base de buprénorphine. Cependant, il existe peu de rapports publiés sur les régimes d'initiation à faible dose dans le cadre de la douleur chronique.Objectifs: L'objectif de cette étude était de décrire une série de cas d'individus vivant avec une douleur chronique qui sont passés d'un traitement opioïde complet à long terme à un traitement par buprénorphine sublinguale/naloxone en ayant recours à des régimes d'initiation à faible dose.Méthodes: Cette étude est une série de cas rétrospective incluant tous les patients pris en charge dans une clinique externe de traitement de la douleur chronique et pour lesquels un schéma d'initiation à faible dose de buprénorphine/naloxone a été programmé entre mars 2020 et décembre 2022. Les données ont été collectées par le biais d'un examen rétrospectif des dossiers médicaux électroniques et les résultats ont été analysés à l'aide de statistiques descriptives.Résultats: Dix-huit patients ont fait la transition des opioïdes de base à la buprénorphine/naloxone en utilisant un régime d'initiation à faible dose. Parmi ces patients, 17 ont terminé l'initiation avec succès (94,44 %), 12 ont présenté des effets indésirables pendant l'initiation (66,67 %) et un seul patient a dû interrompre son traitement. Tous les effets indésirables ont disparu une fois les doses d'entretien de buprénorphine/naloxone établies. Le score d'impression clinique globale-amélioration moyen après le début du traitement était de 2 (1-5).Conclusion: L'initiation à faible dose est une approche efficace pour faire passer les patients souffrant de douleur chronique non cancéreuse d'un traitement opioïde à long terme à la buprénorphine/naloxone sans complications majeures ni aggravation de la douleur.
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OBJECTIVE: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD). METHOD: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24. RESULTS: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use. CONCLUSIONS: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27th, 2017, prior to participants enrollment.
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BACKGROUND AND AIM: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use. DESIGN, SETTING AND PARTICIPANTS: This was a population-based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada. All individuals with at least one OAT dispensation in BC between 1 January 2014 and 31 August 2021 took part. MEASUREMENTS: To assess changes in OAT prescribing practices over time, we calculated initiation doses, dose titration intervals, maintenance doses and take-home dosing intervals stratified by medication [methadone, buprenorphine-naloxone and slow-release oral morphine (SROM)] according to recommended guidelines. FINDINGS: A total of 265 410 OAT episodes (57.5% on methadone, 34.5% on buprenorphine-naloxone and 8.0% on SROM) were initiated during the study period. Compared with the guideline recommendation, observed initiation doses were higher among all medications from 2014 (2017 for SROM) to 2021 (buprenorphine-naloxone: 14-29%; methadone: 53-66%; SROM: 26-55%). Titration intervals were shorter for all medications, consistent with guidelines for buprenorphine-naloxone (26-49%), but shorter than recommended for methadone or SROM (28-51% and 12-41%, respectively). Higher maintenance dosing was observed for methadone (68-78%) and SROM (3-21%). Take-home allowances extending beyond the recommended guideline length increased across medications (buprenorphine-naloxone: 18-35%; methadone: 50-64%; SROM: 34-39%). Changes in prescribing patterns were similar for first-time OAT initiators. CONCLUSION: In British Columbia, Canada, from 2014 to 2021, prescribers of opioid agonist treatment (OAT) appeared to initiate both new and experienced OAT clients at higher doses than guideline recommendations, titrate them more rapidly and maintain clients at higher doses. Take-home dose allowances also gradually increased.
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Background: Buprenorphine initiation in opioid-tolerant patients usually requires decreasing the total opioid intake per day due to its potential for precipitating withdrawal. However, this strategy may not be tolerated in patients who require higher amounts of opioids, such as those with cancer pain. Case Presentation: We utilized a buprenorphine microdosing strategy for a postoperative cancer patient who was previously taking buprenorphine-naloxone for chronic noncancer pain, then initiated on methadone for uncontrolled cancer-related pain. He had a planned cancer resection in the hospital. He subsequently underwent a successful transition from methadone to buprenorphine-naloxone through microdosing in one week with close monitoring in the inpatient setting. Conclusions: Using a microdosing strategy to transition from methadone to buprenorphine-naloxone in a span of days was achieved in this case report. More research regarding the feasibility and tolerability of microinductions is needed, especially in the setting of chronic pain or cancer-related pain.
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OBJECTIVE: To get information on subcutaneous extended-release buprenorphine as opioid maintenance treatment during pregnancy, we compared it to orally administered buprenorphine and buprenorphine-naloxone treatments. We hypothesized that maternal and neonatal outcomes do not differ between the treatment groups. Study design In this population-based cohort study, 60 pregnant individuals receiving non-changed opioid maintenance treatment for opioid use disorder with a buprenorphine product from the time before conception to the time after delivery and their newborns were included. They were divided into three groups based on the pharmacotherapy with subcutaneous extended-release buprenorphine, sublingual buprenorphine, or buprenorphine-naloxone. Statistical analyses were conducted using Fischer's exact tests, ANOVA tests, and Kruskal-Wallis tests. All the statistical tests were two-tailed. RESULTS: The frequency of pregnancy or delivery complications did not significantly differ between the group receiving extended-release buprenorphine and the other groups. During pregnancy, 38 % of the women used illicit drugs concomitantly, with equal frequency in the extended-release buprenorphine group and the other groups. Of the neonates, 93 % were born full-term and 90 % got at least eight Apgar points in one minute age, without significant differences between the groups (p = 0.57). The need for pharmacotherapy for neonatal opioid withdrawal syndrome was the lowest in the extended-release buprenorphine group (25 %) and highest in the sublingual buprenorphine group (67 %). Still, the difference between the treatment groups did not reach statistical significance (p = 0.17). Among all neonates, the breastfed infants were less likely to receive pharmacotherapy for withdrawal symptoms than the formula-fed ones (p = 0.048). CONCLUSIONS: Extended-release buprenorphine with steady drug concentration seems to be a promising pharmacotherapy option during pregnancy for mothers. Maternal health during pregnancy may contribute to the well-being of newborns. Larger trials are urgently needed to confirm these results..
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Background: Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Results: Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Conclusions: Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.
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BACKGROUND: Breastfeeding among lactating people with opioid use disorder taking buprenorphine monotherapy is generally accepted, as low concentrations of buprenorphine and metabolites in human milk have been well-established. The use of buprenorphine-naloxone for pregnant and lactating people with opioid use disorder is expanding and there is no information available regarding the concentrations of naloxone and their metabolites in human milk to recommend the use of this combination medication during lactation. RESEARCH AIMS: To determine the concentrations of buprenorphine and naloxone and their primary metabolites in human milk, maternal plasma, and infant plasma, among lactating buprenorphine-naloxone maintained people and their infants. METHODS: Four lactating buprenorphine-naloxone maintained people provided plasma and human milk samples on Days 2, 3, 4, 14, and 30 postpartum. Infant plasma was obtained on Day 14. RESULTS: Concentrations of buprenorphine, norbuprenorphine and their glucuronide metabolites were present in maternal plasma and human milk at low concentrations, consistent with previous research in lactating buprenorphine monotherapy participants. Naloxone was not detected, or was detected at concentrations below the limit of quantification, in maternal plasma and in all except one human milk sample at Day 30. Naloxone was not detected or detected at concentrations below the limit of quantification in all infant plasma samples. CONCLUSION: Results support the use of buprenorphine-naloxone by lactating people who meet appropriate criteria for breastfeeding.
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Buprenorfina, Transtornos Relacionados ao Uso de Opioides, Lactente, Feminino, Gravidez, Humanos, Lactação/metabolismo, Aleitamento Materno, Combinação Buprenorfina e Naloxona, Buprenorfina/uso terapêutico, Naloxona/farmacologia, Naloxona/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Analgésicos Opioides/uso terapêuticoRESUMO
INTRODUCTION: In clinical practice, sublingual (SL) buprenorphine-naloxone is prescribed as once daily or split daily dosing for the management of opioid use disorder (OUD). Evidence is lacking that assesses how split daily buprenorphine-naloxone affects OUD outcomes. This study aims to evaluate how the dosing frequency of SL buprenorphine-naloxone impacts therapy effectiveness when treating patients with OUD. METHODS: This retrospective analysis included adult outpatients prescribed treatment with SL buprenorphine-naloxone for OUD between July 1, 2016, and March 1, 2020. The study excluded patients with sickle cell disease, recent methadone treatment, or pregnancy. We characterized study groups by dosing frequency, either once daily or split dosing. The study compared retention in treatment, medication adherence, adherence to treatment program, and hospital encounters between groups. RESULTS: The study screened eight-hundred and seven patients, and included 250 patients newly prescribed SL buprenorphine-naloxone. Fifty-seven patients (22.8 %) were prescribed once daily dosing and 193 patients (77.2 %) were prescribed split daily dosing. The study found no significant differences noted in 12-month rates of treatment retention (52.6 % vs. 45.6 %, p = .35). These outcomes remained similar when assessed at three and six months. Within a year of buprenorphine-naloxone initiation, the study found no differences in the percentage of patients with hospitalizations (26.3 % vs. 38.3 %, p = .10), median number of hospitalizations (2 vs. 2), or proportion of days covered by a prescription ≥80 % (93.3 % vs. 92.0 %, p = .82). CONCLUSIONS: In this study, patients receiving once daily buprenorphine-naloxone had similar treatment outcomes to patients receiving split dosing. Further controlled studies are necessary to evaluate which patients are more likely to benefit from split dosing.
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Buprenorfina, Transtornos Relacionados ao Uso de Opioides, Adulto, Humanos, Combinação Buprenorfina e Naloxona/uso terapêutico, Antagonistas de Entorpecentes, Estudos Retrospectivos, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Resultado do TratamentoRESUMO
BACKGROUND: Buprenorphine is a medication that is used to treat opioid use disorder by reducing withdrawal symptoms and cravings for opioids. Patients with poor adherence are at higher risk of relapse and overdose. Providers often test adherence through urine testing but are not aware of simulated adherence, where patients may directly add buprenorphine to the urine samples. As of now, there exists no literature on the simulated adherence practices for patients who stayed in the treatment for more than three months. METHODS: This study is a cross-sectional analysis of simulated adherence through urine toxicology results of 3950 patients undergoing buprenorphine/naloxone treatment. Simulated adherence was measured by the ratio of norbuprenorphine and buprenorphine <0.02 in the urine sample. Descriptive statistics as well as multivariate analysis was conducted to examine the relationship between patient information and outcomes. RESULTS: Out of 3950 patients, 411 (10.4%) had a history of one or more simulated adherence. On average, patients with multiple simulated adherences had 48.1% of their tests simulated, while on the contrary, patients with a single occurrence of simulated adherence had 17.6% of their tests simulated. Weekly testing and visit number of over 15 were associated with a higher likelihood of simulated adherence. CONCLUSION: The study demonstrates that simulated adherence is a recurring phenomenon among buprenorphine/naloxone treatment patients regardless of the duration in the treatment. Utilization of quantitative urine toxicology to identify simulated adherence will enable healthcare providers to formulate a more precise and effective treatment plan tailored to support individual patient needs.
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Objective: To assess whether Maryland community pharmacies had Suboxone available for dispensing. Methods: This cross-sectional study used a secret shopper model to contact public-facing community pharmacies in Maryland. The secret shopper, guided by a script, asked whether a prescription for Suboxone was available for the same or next day pick-up. A small convenience sample of pharmacies who did not have Suboxone available received an in-person visit to inquire about medication availability and dispensing barriers. Results: After contacting 99% (n = 1046) of Maryland public-facing pharmacies, Suboxone was confirmed available for immediate pick-up in 31% (n = 326). The remaining did not have, would not disclose, or had limited access (existing patients or specific providers only). Significant differences in Suboxone availability were found for National Capital vs. Baltimore metro region and when pharmacist asked questions vs. no questions. Of the 11 pharmacy visits completed, 10 said they had Suboxone currently in stock, with one clarifying medication was for existing patients only. Conclusion: About 69% of patients may face challenges when calling to find out whether they can obtain Suboxone in Maryland pharmacies. Better patient education and more thorough pharmacy-level investigation of system and workflow barriers could offer solutions.
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BACKGROUND AND OBJECTIVE: First 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. METHOD: A 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. RESULTS: Among 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. CONCLUSION: There 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.
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Buprenorfina, Transtornos Relacionados ao Uso de Opioides, Masculino, Humanos, Feminino, Antagonistas de Entorpecentes/uso terapêutico, Naltrexona/uso terapêutico, Combinação Buprenorfina e Naloxona/uso terapêutico, Analgésicos Opioides/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Doença Crônica, Recidiva, Preparações de Ação Retardada/uso terapêutico, Injeções IntramuscularesRESUMO
OBJECTIVES: Many emergency department (ED) patients with opioid use disorder are candidates for home buprenorphine/naloxone initiation with to-go packs. We studied patient opinions and acceptance of buprenorphine/naloxone to-go packs, and factors associated with their acceptance. METHODS: We identified patients at two urban EDs in British Columbia who met opioid use disorder criteria, were not presently on opioid agonist therapy and not in active withdrawal. We offered patients buprenorphine/naloxone to-go as standard of care and then administered a survey to record buprenorphine/naloxone to-go acceptance, the primary outcome. Survey domains included current substance use, prior experience with opioid agonist therapy, and buprenorphine/naloxone related opinions. Patient factors were examined for association with buprenorphine/naloxone to-go acceptance. RESULTS: Of the 89 patients enrolled, median age was 33 years, 27% were female, 67.4% had previously taken buprenorphine/naloxone, and 19.1% had never taken opioid agonist therapy. Overall, 78.7% believed that EDs should dispense buprenorphine/naloxone to-go packs. Thirty-eight (42.7%) patients accepted buprenorphine/naloxone to-go. Buprenorphine/naloxone to-go acceptance was associated with lack of prior opioid agonist therapy, less than 10 years of opioid use and no injection drug use. Reasons to accept included initiating treatment while in withdrawal; reasons to reject included prior unsatisfactory buprenorphine/naloxone experience and interest in other treatments. CONCLUSION: Although less than half of our study population accepted buprenorphine/naloxone to-go when offered, most thought this intervention was beneficial. In isolation, ED buprenorphine/naloxone to-go will not meet the needs of all patients with opioid use disorder. Clinicians and policy makers should consider buprenorphine/naloxone to-go as a low-barrier option for opioid use disorder treatment from the ED when integrated with robust addiction care services.
RéSUMé: OBJECTIFS: De nombreux patients des services d'urgence (SU) atteints d'un trouble lié à la consommation d'opioïdes sont des candidats à l'initiation à la buprénorphine/naloxone à domicile avec des trousses à emporter. Nous avons étudié les opinions des patients et l'acceptation des paquets de buprénorphine/naloxone à emporter, ainsi que les facteurs associés à leur acceptation. MéTHODES: Nous avons identifié des patients à deux urgences urbaines de la Colombie-Britannique qui répondaient aux critères relatifs aux troubles liés à l'utilisation d'opioïdes, qui ne suivaient pas actuellement un traitement aux agonistes des opioïdes et qui n'étaient pas en sevrage actif. Nous avons offert aux patients la buprénorphine/naloxone à emporter comme norme de soins, puis nous avons administré une enquête pour enregistrer l'acceptation de la buprénorphine/naloxone à emporter, le critère de jugement principal. Les domaines d'enquête comprenaient la consommation actuelle de substances, l'expérience antérieure avec le traitement aux agonistes opioïdes et les opinions liées à la buprénorphine/naloxone. Les facteurs du patient ont été examinés pour déterminer l'association avec l'acceptation de la buprénorphine/naloxone à emporter. RéSULTATS: Sur 89 patients inscrits, l'âge médian était de 33 ans, 27,0% étaient des femmes, 67,4% avaient déjà pris de la buprénorphine/naloxone et 19,1% n'avaient jamais pris de traitement aux agonistes opioïdes. Dans l'ensemble, 78,7% des répondants étaient d'avis que les SU devraient distribuer des paquets de buprénorphine/naloxone à emporter. Trente-huit (42,7%) patients ont accepté la buprénorphine/naloxone à emporter. L'acceptation de la buprénorphine/naloxone à emporter était associée à l'absence de traitement antérieur par agonistes opioïdes, à moins de 10 ans d'utilisation d'opioïdes et à l'absence de consommation de drogues injectables. Les raisons d'accepter comprenaient le fait de commencer un traitement pendant le sevrage; les raisons de rejeter comprenaient une expérience antérieure insatisfaisante de buprénorphine/naloxone et un intérêt pour d'autres traitements. CONCLUSION: Bien que moins de la moitié de notre population à l'étude ait accepté la buprénorphine/naloxone à emporter lorsqu'elle lui était offerte, la plupart ont pensé que cette intervention était bénéfique. Isolément, la buprénorphine/naloxone à emporter à l'urgence ne répondra pas aux besoins de tous les patients atteints de troubles liés à l'utilisation d'opioïdes. Les cliniciens et les décideurs devraient considérer la buprénorphine/naloxone à emporter comme une option à faible barrière pour le traitement des troubles liés à la consommation d'opioïdes par l'urgence lorsqu'elle est intégrée à de solides services de soins de la toxicomanie.
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Antagonistas de Entorpecentes, Transtornos Relacionados ao Uso de Opioides, Humanos, Feminino, Adulto, Masculino, Antagonistas de Entorpecentes/uso terapêutico, Analgésicos Opioides/uso terapêutico, Combinação Buprenorfina e Naloxona/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Transtornos Relacionados ao Uso de Opioides/epidemiologia, Serviço Hospitalar de EmergênciaRESUMO
Background: 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). Methods: 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. Results: 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. Conclusion: 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.
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BACKGROUND: In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD). METHODS: Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD. RESULTS: We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD. CONCLUSIONS: Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.
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Buprenorfina, COVID-19, Transtornos Relacionados ao Uso de Opioides, Humanos, Analgésicos Opioides/uso terapêutico, Análise de Séries Temporais Interrompida, Pandemias, COVID-19/epidemiologia, Transtornos Relacionados ao Uso de Opioides/epidemiologia, Colúmbia Britânica/epidemiologia, Metadona/uso terapêutico, Combinação Buprenorfina e Naloxona, Derivados da Morfina, Buprenorfina/uso terapêutico, Tratamento de Substituição de OpiáceosRESUMO
OBJECTIVES: Opioid use disorder is a major public health concern that accounts for a high number of potential years of life lost. Buprenorphine/naloxone is a recommended treatment for opioid use disorder that can be started in the emergency department (ED). We developed an ED-based program to initiate buprenorphine/naloxone for eligible patients who live with opioid use disorder, and to provide unscheduled, next-day follow-up referrals to an opioid use disorder treatment clinic (in person or virtual) for continuing patient care throughout Alberta. METHODS: In this quality improvement initiative, we supported local ED teams to offer buprenorphine/naloxone to eligible patients presenting to the ED with suspected opioid use disorder and refer these patients for follow-up care. Process, outcome, and balancing measures were evaluated over the first 2 years of the initiative (May 15, 2018-May 15, 2020). RESULTS: The program was implemented at 107 sites across Alberta during our evaluation period. Buprenorphine/naloxone initiations in the ED increased post-intervention at most sites with baseline data available (11 of 13), and most patients (67%) continued to fill an opioid agonist prescription at 180 days post-ED visit. Of the 572 referrals recorded at clinics, 271 (47%) attended their first follow-up visit. Safety events were reported in ten initiations and were all categorized as no harm to minimal harm. CONCLUSIONS: A standardized provincial approach to initiating buprenorphine/naloxone in the ED for patients living with opioid use disorder was spread to 107 sites with dedicated program support staff and adjustment to local contexts. Similar quality improvement approaches may benefit other jurisdictions.
ABSTRAIT: OBJECTIFS: Le trouble lié à la consommation d'opioïdes est une préoccupation majeure en santé publique qui explique le nombre élevé d'années potentielles de vie perdues. La buprénorphine/naloxone est un traitement recommandé pour le trouble lié à l'utilisation d'opioïdes qui peut être commencé au service des urgences (SU). Nous avons mis au point un programme axé sur les urgences pour commencer la buprénorphine/naloxone pour les patients éligibles qui vivent avec un trouble lié à l'utilisation d'opioïdes, et pour fournir suivis des cas référés le jour suivant vers une clinique de soins des troubles liés à l'utilisation d'opioïdes (sur place ou virtuelle) pour les soins continus aux patients partout en Alberta. MéTHODES: Dans le cadre de cette initiative d'amélioration de la qualité, nous avons aidé les équipes locales de SU à offrir la buprénorphine/naloxone aux patients admissibles qui se présentent à la SU avec un trouble présumé de consommation d'opioïdes et à les diriger vers des soins de suivi. Le processus, les résultats et les mesures d'équilibre ont été évalués au cours des deux premières années de l'initiative (du 15 mai 2018 au 15 mai 2020). RéSULTATS: Le programme a été mis en Åuvre dans 107 sites en Alberta pendant notre période d'évaluation. Les initiations à la buprénorphine/naloxone à l'urgence ont augmenté après l'intervention dans la plus grande partie de sites pour lesquels des données de référence étaient disponibles (11 sur 13), et la plupart des patients (67 %) ont continué de remplir une ordonnance d'agonistes opioïdes 180 jours après la visite à l'urgence. Sur les 572 renvois enregistrés aux cliniques, 271 (47 %) ont assisté à leur première visite de suivi. Des événements liés à la sécurité ont été signalés dans 10 initiatives et ont tous été classés comme n'ayant causé aucun conséquences à des conséquences minimes. CONCLUSIONS: Une approche provinciale standardisé de lancement de la buprénorphine/naloxone à l'urgence pour les patients atteints d'un trouble lié à la consommation d'opioïdes a été diffusée à 107 sites à l'aide de soutien aux programmes spécialisé et des ajustements aux contextes locaux. Des approches semblables d'amélioration de la qualité pourraient profiter à d'autres juridictions.
Assuntos
Buprenorfina, Transtornos Relacionados ao Uso de Opioides, Humanos, Antagonistas de Entorpecentes/uso terapêutico, Buprenorfina/uso terapêutico, Alberta/epidemiologia, Melhoria de Qualidade, Combinação Buprenorfina e Naloxona/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Transtornos Relacionados ao Uso de Opioides/epidemiologia, Serviço Hospitalar de Emergência, Encaminhamento e Consulta, Analgésicos Opioides/uso terapêuticoRESUMO
INTRODUCTION: Limited research examines buprenorphine-naloxone interest among adolescents and young adults (AYA). This longitudinal study examined factors associated with initial buprenorphine-naloxone interest and the time to a positive change in buprenorphine-naloxone interest or enrollment, in addition to identifying reasons for buprenorphine-naloxone disinterest. METHODS: The study derived data from a cohort of street-involved AYA in Vancouver, Canada between December 2014 and June 2018. The analysis was restricted to AYA who reported weekly or daily illicit opioid use in the last six months but had not initiated buprenorphine-naloxone. The study examined factors associated with initial buprenorphine-naloxone interest using multivariable logistic regression, while multivariable Cox regression identified factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up among AYA initially disinterested in buprenorphine-naloxone. RESULTS: Of 281 participants who reported weekly illicit opioid use but were not on buprenorphine-naloxone, 52 (18.5 %) AYA reported initial buprenorphine-naloxone interest, while 68 (24.2 %) AYA who were initially disinterested in buprenorphine-naloxone reported interest or enrollment over follow-up. In multivariable logistic regression, initial interest was positively associated with older age (Adjusted Odds Ratio [AOR] = 1.09, 95 % Confidence Interval [CI]: 1.03-1.15), but negatively associated with self-reported Indigenous identity (AOR = 0.22, 95 % CI: 0.07-0.68). In multivariable Cox regression, recent detoxification program access (Adjusted Hazard Ratio [AHR] = 0.85, 95 % CI: 0.73-0.98) was positively associated with the time to a positive change in buprenorphine-naloxone interest or enrollment. Common reasons for buprenorphine-naloxone disinterest included not wanting opioid agonist treatments (OAT) (initial n = 67, follow-up n = 105); not wanting to experience precipitated withdrawal (initial n = 42, follow-up n = 54), being satisfied with or preferring other OAT (initial n = 33, follow-up n = 52), not knowing what buprenorphine-naloxone is (initial n = 27, follow-up n = 9), previous negative treatment experiences (initial n = 19, follow-up n = 20), and wanting to continue opioid use (initial n = 13, follow-up n = 9), among others. CONCLUSIONS: We documented persistent disinterest in buprenorphine-naloxone among AYA, though participants' reasons for disinterest provide insight into the potential benefits of expanding micro-dosing induction; ensuring treatment is culturally safe; and communicating changes in buprenorphine-naloxone programming to AYA. Nevertheless, a need remains to improve the continuum of harm reduction and treatment supports for AYA.
Assuntos
Combinação Buprenorfina e Naloxona, Transtornos Relacionados ao Uso de Opioides, Adolescente, Adulto Jovem, Humanos, Combinação Buprenorfina e Naloxona/uso terapêutico, Analgésicos Opioides/uso terapêutico, Estudos Longitudinais, Estudos Prospectivos, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Canadá/epidemiologiaRESUMO
Background: Although buprenorphine/naloxone has been demonstrated to be an effective treatment for patients with opioid use disorder (OUD), treatment retention has been a challenge. This study extends what is presently a limited literature regarding patients' experiences with this medication and the implications for treatment retention. Methods: The study was conducted as a qualitative investigation of patients in treatment for OUD at the time of the study. Forty-three patients (27 men, 15 women, mean age 34.7) were recruited from three clinical settings, a community health center, an academically-based treatment site, and an independent substance abuse treatment facility. Most patients had returned to use in the past after attempts to become abstinent. Results: Patients generally reported positive experiences with this medication noting it helped to reduce opioid cravings quickly. As important considerations for treatment retention, patients emphasized a firm commitment to achieving abstinence when beginning treatment and a prescriber who is informed about and attentive to their emotional state. Diverging attitudes did exist regarding treatment duration as some patients were accepting of long-term treatment while others desired a relatively brief option. Among patients who had returned to use, potentially important issues emerged pertaining to the absence of patient outreach for missed medication appointments and inadequate discharge planning following stays at rehabilitation facilities. Conclusions: While results regarding the importance of patient motivation and strong patient-prescriber relationships have been noted in previous studies, other findings regarding opportunities to improve patient outreach and coordination of care have received relatively less attention and warrant further consideration.
Assuntos
Buprenorfina, Transtornos Relacionados ao Uso de Opioides, Masculino, Humanos, Feminino, Adulto, Buprenorfina/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Transtornos Relacionados ao Uso de Opioides/reabilitação, Combinação Buprenorfina e Naloxona/uso terapêutico, Analgésicos Opioides/uso terapêutico, Atitude, Tratamento de Substituição de Opiáceos/métodos, Antagonistas de Entorpecentes/uso terapêuticoRESUMO
BACKGROUND AND AIM: While daily witnessed opioid agonist treatment (OAT) ingestion is common in British Columbia (BC), Canada, and elsewhere, sparse evidence supports this resource-intensive practice. Many settings across North America relaxed restrictions for take-home dosing during the COVID-19 pandemic and have reported consistent or improved patient outcomes. This study measured excess expenditures attributed to daily witnessed pharmacy dispensing compared with weekly or biweekly dispensation schedules. DESIGN, SETTING AND PARTICIPANTS: This study was a population-level retrospective analysis. We included all methadone, buprenorphine/naloxone and slow-release oral morphine dispensations in BC from 1 January 2014 to 30 December 2020. A total of 24 357 107 OAT dispensations among 51 195 unique individuals with 122 793 person-years of follow-up were included during the study period. MEASUREMENTS: Total expenditures for each person-week of OAT with an estimated expenditure under two scenarios are as follows: (1) a weekly dispensation scenario and (2) a biweekly dispensation scenario. FINDINGS: We estimated excess expenditures attributable to current dispensing practices of between $38 million (2014) and $47.4 million (2018) compared with a hypothetical weekly dispensing schedule, and $43.9 million (2014) to $54.9 million (2018) compared with biweekly dispensing. The majority of these expenditures (58-64%) were attributed to pharmacy dispensing fees ($23 million in 2014 to $30 million in 2018 compared with weekly dispensing; $26.6 million in 2014 to $34.7 million in 2018 compared with biweekly dispensing). CONCLUSION: Daily witnessed opioid agonist treatment ingestion results in more than $30 million in excess expenditures annually in the province of British Columbia, Canada compared with the costs of weekly or biweekly dispensation schedules.
Assuntos
Buprenorfina, COVID-19, Transtornos Relacionados ao Uso de Opioides, Humanos, Analgésicos Opioides/uso terapêutico, Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico, Colúmbia Britânica, Gastos em Saúde, Estudos Retrospectivos, Pandemias, Metadona/uso terapêutico, Tratamento de Substituição de Opiáceos/métodos, Ingestão de Alimentos, Buprenorfina/uso terapêuticoRESUMO
The prevalence of opioid use among pregnant people has been increasing over the past few decades, with a parallel increase in the rate of neonatal abstinence syndrome. Opioid agonist treatment (OAT) including methadone and buprenorphine is the recommended management method for opioid use disorders during pregnancy. Methadone has been extensively studied during pregnancy; however, buprenorphine was introduced in the early 2000s with limited data on the use of different preparations during pregnancy. Buprenorphine-naloxone has been incorporated into routine practice; however, only a few studies have investigated the use of this medication during pregnancy. To determine the safety and efficacy of this medication, we conducted a systematic review of maternal and neonatal outcomes among buprenorphine-naloxone-exposed pregnancies. The primary outcomes of interest were birth parameters, congenital anomalies, and severity of neonatal abstinence syndrome. Secondary maternal outcomes included the OAT dose and substance use at delivery. Seven studies met the inclusion criteria. Buprenorphine-naloxone doses ranged between 8 and 20 mg, and there was an associated reduction of opioid use during pregnancy. There were no significant differences in gestational age at delivery, birth parameters, or prevalence of congenital anomalies between buprenorphine-naloxone-exposed neonates and those exposed to methadone, buprenorphine monotherapy, illicit opioids, or no opioids. In studies comparing buprenorphine-naloxone to methadone, there were reduced rates of neonatal abstinence syndrome requiring pharmacotherapy. These studies demonstrate that buprenorphine-naloxone is a safe and effective opioid agonist treatment for pregnant people with OUD. Further large-scale, prospective data collection is required to confirm these findings. Patients and clinicians may be reassured about the use of buprenorphine-naloxone during pregnancy.
