RESUMEN
BACKGROUND: Sublingual buprenorphine, approved for treatment of opioid use disorder since 2002, is most commonly available in co-formulation with naloxone. Naloxone is an opioid antagonist minimally absorbed when sublingual (SL) buprenorphine/naloxone is taken as prescribed; it is thought to reduce potential for misuse via intravenous administration. However, growing data and clinical experience demonstrate that previously accepted assumptions about the pharmacokinetics of these medications may not apply to all patients. CASE PRESENTATION: We present a patient whose adverse post-administration side effects on SL buprenorphine/naloxone resolved with transition to SL buprenorphine monoproduct. DISCUSSION: Naloxone can be detected in nearly all patients taking SL buprenorphine/naloxone, though with apparent variability in clinical effect. In a minority of patients, naloxone can contribute to adverse and potentially treatment-limiting side effects. Furthermore, the naloxone component is commonly misunderstood by patients and providers and can foster mistrust in the therapeutic relationship if providers are perceived to be withholding a more tolerable formulation. Prescribers should have a low threshold to offer buprenorphine alone when clinically appropriate.
Asunto(s)
Combinación Buprenorfina y Naloxona , Antagonistas de Narcóticos , Trastornos Relacionados con Opioides , Adulto , Femenino , Humanos , Administración Sublingual , Buprenorfina/uso terapéutico , Combinación Buprenorfina y Naloxona/efectos adversos , Naloxona/efectos adversos , Antagonistas de Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
OBJECTIVE: Dose optimization plays a key role in determining clinical outcomes in patients on opioid agonist treatment (OAT). The objective of this study was to identify the variables independently associated with buprenorphine/naloxone (B/N) dose adequacy in patients with opiate use disorder (OUD). METHOD: Cross-sectional study of a convenience sample of patients with OUD treated with B/N (n = 315) in four regions in Spain. The Opiate Dosage Adequacy Scale (ODAS) was used to determine B/N dose adequacy. The ODAS evaluate the six components of the "dose adequacy" construct, as follows: continued use of heroin; narcotic blockade or crossed tolerance; objective opioid withdrawal symptoms (OWS); subjective OWS; craving for heroin; and overmedication. A binomial logistic regression analysis was performed to identify the variables associated with the condition "ODAS Adequate B/N dose". Participants completed a battery of instruments to assess sociodemographic, substance use, clinical, and treatment variables. RESULTS: The B/N dose was considered adequate in 231 of the 315 participants (73.3 %). Two variables, satisfaction with B/N as a medication (OR=5.764, 95 % CI=2.211-15.030) and patient-perceived participation in B/N dose decisions (OR=1.790, 95 % CI=1221-2623), were independently, significantly, and positively associated with the "ODAS Adequate B/N dose" condition. While the severity of heroin dependence was significantly associated with buprenorphine dose adequacy in the bivariate analyses, significance was lost in the full regression model. CONCLUSION: Satisfaction with B/N as a medication and patient-perceived involvement in the dose decision are associated with clinician-assessed dose adequacy. In the context of good clinical practice, it is important to take into account both of these variables to individualize the prescribed dose through a shared decision-making process.
Asunto(s)
Combinación Buprenorfina y Naloxona , Buprenorfina , Antagonistas de Narcóticos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Masculino , Adulto , Femenino , Estudios Transversales , Buprenorfina/administración & dosificación , Persona de Mediana Edad , Antagonistas de Narcóticos/administración & dosificación , Combinación Buprenorfina y Naloxona/administración & dosificación , España , Relación Dosis-Respuesta a Droga , Satisfacción del Paciente , Analgésicos Opioides/administración & dosificación , Síndrome de Abstinencia a Sustancias/tratamiento farmacológicoRESUMEN
OBJECTIVES: Although research has continued to show that substance use disorders (SUDs) can be treated effectively with evidence-based treatment, there continues to be gaps in access, and utilization remains low. Alternative SUD treatment methods, including telemedicine, are increasingly being explored to reach patients where traditional in-person treatment approaches are inaccessible. This cross-sectional study aimed to explore SUD treatment retention, specifically comparing telemedicine-delivered opioid use disorder (OUD) treatment with a traditional in-person treatment delivery approach. METHODS: Patients at Cahaba Medical Care, an FQHC in Birmingham, AL with a diagnosis of OUD and undergoing buprenorphine/naloxone or buprenorphine treatment were categorized into two groups: treatment and control. The dependent variable, retention to SUD treatment, was assessed at four different time periods over 12 months to determine patient SUD consultation appointment attendance. Multiple linear regression was used to examine the relationship between SUD treatment retention and delivery mode. Correlations were obtained to assess associations between frequency of urine drug screens performed and SUD treatment retention. RESULTS: As the number of the urine drug screens patients received increased by 1, the number of SUD treatment program consultations patients attended increased by 0.69 (P < 0.001). There was no significant difference in SUD treatment retention between traditional in-person and telemedicine delivered approaches, however. CONCLUSIONS: The findings of this study suggest that a telemedicine-delivered treatment program equals retention effectiveness when compared with in-person delivery. This suggests that leveraging telemedicine to treat patients with SUD could be an effective alternative for those unable to access treatment or who are less likely to attend or complete traditional in-person treatment sessions.
Asunto(s)
Trastornos Relacionados con Opioides , Telemedicina , Humanos , Telemedicina/estadística & datos numéricos , Estudios Transversales , Masculino , Femenino , Adulto , Trastornos Relacionados con Opioides/terapia , Trastornos Relacionados con Opioides/tratamiento farmacológico , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/métodos , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Sustancias/terapia , Retención en el Cuidado/estadística & datos numéricos , Buprenorfina/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
INTRODUCTION: There is uncertainty about whether criminal legal involvement (CLI) impacts the effectiveness of medications for opioid use disorder (MOUD). We aimed to determine whether CLI modifies the association between buprenorphine-naloxone (BUP-NX) vs. extended-release naltrexone (XR-NTX) and MOUD treatment outcomes. METHODS: We conducted a secondary analysis of X:BOT, a 24-week multi-center randomized controlled trial comparing treatment outcomes between BUP-NX (n = 287) and XR-NTX (n = 283) in the general population. We used baseline Additional Severity-Index Lite responses to identify patients with recent CLI (n = 342), defined as active CLI and/or CLI in the past 30 days, and lifetime incarceration (n = 328). We explored recent CLI and lifetime incarceration as potential effect modifiers of BUP-NX vs. XR-NTX effectiveness on relapse, induction, and overdose. We conducted both intention-to-treat and per-protocol analyses for each outcome. RESULTS: In intention-to-treat analyses, recent CLI modified the effect of BUP-NX vs. XR-NTX on odds of successful induction (p = 0.03) and hazard of overdose (p = 0.04), but it did not modify the effect on hazard of relapse (p = 0.23). All participants experienced lower odds of successful induction with XR-NTX compared to BUP-NX, but the relative likelihood of successful induction with BUP-NX was lower than XR-NTX among individuals with recent CLI (OR: 0.25, 95 % CI: 0.13-0.47, p < 0.001) compared to those without recent CLI (OR: 0.04, 95 % CI: 0.01-0.19, p < 0.001). Participants with recent CLI experienced similar hazard of overdose with XR-NTX and BUP-NX (HR: 1.12, 95 % CI: 0.42-3.01, p = 0.82), whereas those without recent CLI experienced greater hazard of overdose with XR-NTX compared to BUP-NX (HR: 12.60, 95 % CI: 1.62-98.03, p = 0.02). In per-protocol analyses, recent CLI did not modify the effect of MOUD on hazard of overdose (p = 0.10) or relapse (p = 0.41). Lifetime incarceration did not modify any outcome. CONCLUSIONS: Compared to individuals without recent CLI, individuals with recent CLI experienced decreased relative effectiveness of BUP-NX compared to XR-NTX for induction and overdose outcomes. This highlights the importance of considering the impact of recent CLI on opioid use disorder treatment outcomes. Future research should explore the mechanisms through which recent CLI modifies MOUD effectiveness and aim to improve MOUD effectiveness for individuals with recent CLI.
Asunto(s)
Combinación Buprenorfina y Naloxona , Preparaciones de Acción Retardada , Naltrexona , Antagonistas de Narcóticos , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Masculino , Adulto , Femenino , Preparaciones de Acción Retardada/uso terapéutico , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Combinación Buprenorfina y Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Tratamiento de Sustitución de Opiáceos/métodos , Criminales/psicología , Sobredosis de Droga/tratamiento farmacológico , RecurrenciaRESUMEN
Importance: Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. Objective: To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. Design, Setting, and Participants: Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. Intervention: Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. Main Outcomes and Measures: Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. Results: Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups. Conclusions and Relevance: In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use. Trial Registration: ClinicalTrials.gov Identifier: NCT02651584.
Asunto(s)
Buprenorfina , Preparaciones de Acción Retardada , Fentanilo , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Fentanilo/administración & dosificación , Fentanilo/uso terapéutico , Masculino , Femenino , Administración Sublingual , Adulto , Método Doble Ciego , Buprenorfina/administración & dosificación , Persona de Mediana Edad , Inyecciones Subcutáneas , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Analgésicos Opioides/administración & dosificación , Tratamiento de Sustitución de Opiáceos/métodos , Combinación Buprenorfina y Naloxona/administración & dosificación , Combinación Buprenorfina y Naloxona/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. CASE PRESENTATION: We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. CONCLUSIONS: This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.
Asunto(s)
Administración Cutánea , Buprenorfina , Preparaciones de Acción Retardada , Trastornos Relacionados con Opioides , Síndrome de Abstinencia a Sustancias , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Masculino , Adulto , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Femenino , Tratamiento de Sustitución de Opiáceos/métodos , Inyecciones Subcutáneas , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Combinación Buprenorfina y Naloxona/administración & dosificación , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
BACKGROUND: Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment. METHODS: The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed. RESULTS: Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity. CONCLUSIONS: Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.
Asunto(s)
Combinación Buprenorfina y Naloxona , Frecuencia Cardíaca Fetal , Trastornos Relacionados con Opioides , Humanos , Femenino , Embarazo , Adulto , Trastornos Relacionados con Opioides/tratamiento farmacológico , Frecuencia Cardíaca Fetal/efectos de los fármacos , Recién Nacido , Adulto Joven , Síndrome de Abstinencia Neonatal , Tratamiento de Sustitución de Opiáceos , Complicaciones del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Buprenorfina/efectos adversos , Tercer Trimestre del Embarazo , Feto/efectos de los fármacos , Antagonistas de NarcóticosRESUMEN
BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.
Asunto(s)
Naltrexona , Antagonistas de Narcóticos , Humanos , Femenino , Embarazo , Recién Nacido , Adulto , Naltrexona/efectos adversos , Naltrexona/administración & dosificación , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Buprenorfina/efectos adversos , Buprenorfina/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Masculino , Combinación Buprenorfina y Naloxona/efectos adversos , Combinación Buprenorfina y Naloxona/uso terapéutico , Combinación Buprenorfina y Naloxona/administración & dosificación , Desarrollo Infantil/efectos de los fármacos , Lactante , Conducta del Lactante/efectos de los fármacos , Estudios Prospectivos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Naloxona/administración & dosificación , Naloxona/efectos adversos , Naloxona/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIMS: People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence-based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID. DESIGN, SETTING AND PARTICIPANTS: This was a cluster-randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program. INTERVENTION AND COMPARATOR: We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre-exposure prophylaxis; and wound care. MEASUREMENTS: The primary outcome was a composite harm mitigation score that captured access to evidence-based services, risk behaviors and adverse health events (range = 0-15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms. FINDINGS: We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: -0.31; 95% confidence interval: -0.70, 0.08; P = 0.13). CONCLUSIONS: This cluster-randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection-drug-focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.
Asunto(s)
Programas de Intercambio de Agujas , Abuso de Sustancias por Vía Intravenosa , Humanos , Femenino , Masculino , Adulto , Baltimore , Infecciones por VIH , Persona de Mediana Edad , Prestación Integrada de Atención de Salud , Combinación Buprenorfina y Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Reducción del Daño , Unidades Móviles de Salud , Hepatitis C , Práctica Clínica Basada en la EvidenciaRESUMEN
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.
Asunto(s)
Combinación Buprenorfina y Naloxona , Depresión , Metadona , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Índice de Severidad de la Enfermedad , Humanos , Trastornos Relacionados con Opioides/complicaciones , Trastornos Relacionados con Opioides/tratamiento farmacológico , Masculino , Femenino , Adulto , Depresión/tratamiento farmacológico , Depresión/complicaciones , Metadona/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificaciónRESUMEN
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.
Asunto(s)
Analgésicos Opioides , Adhesión a Directriz , Metadona , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Pautas de la Práctica en Medicina , Humanos , Colombia Británica , Estudios Retrospectivos , Masculino , Pautas de la Práctica en Medicina/estadística & datos numéricos , Metadona/uso terapéutico , Metadona/administración & dosificación , Femenino , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Adhesión a Directriz/estadística & datos numéricos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Persona de Mediana Edad , Combinación Buprenorfina y Naloxona/uso terapéutico , Morfina/administración & dosificación , Morfina/uso terapéutico , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: The relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use. METHODS: Data came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder. Participants were randomly allocated to buprenorphine/naloxone or methadone models of care. 270 people with prescription-type opioid use disorder were included in analyses. There were 93 women (34.4%) and 2 transgender (0.7%) participants. Most participants were white (67.4%), 45.9% reported unstable living conditions, and 44.8% had psychiatric comorbidities. Generalized linear mixed models followed by mediation analysis estimated the direct effect of treatment group on Timeline Followback-reported next-week opioid use and the indirect effect through past 24-hour opioid craving measured using the Brief Substance Craving Scale at week 2, 6, 10, 14, 18 and 22. RESULTS: Upon mediation analysis, the average direct effect of treatment on opioid use was 0.465 (95 % CI = 0.183 to 0.751, p < 0.001). The average causal mediated effect was 0.144 (95 % CI = 0.021 to 0.110; p < 0.001). Craving accounted for 23.6 % of the effect of treatment on opioid use (p < 0.001). CONCLUSIONS: Past 24-hour craving was associated with increased next-week opioid use; however, craving only partially mediated the effect of buprenorphine/naloxone and methadone on next-week opioid use. Research is needed to develop a comprehensive understanding of factors mediating opioid use during opioid agonist therapy.
Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Femenino , Humanos , Analgésicos Opioides/uso terapéutico , Ansia , Tratamiento de Sustitución de Opiáceos/métodos , Canadá/epidemiología , Trastornos Relacionados con Opioides/psicología , Combinación Buprenorfina y Naloxona/uso terapéutico , Metadona/uso terapéutico , Buprenorfina/uso terapéutico , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
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..
Asunto(s)
Buprenorfina , Preparaciones de Acción Retardada , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Trastornos Relacionados con Opioides/tratamiento farmacológico , Tratamiento de Sustitución de Opiáceos/métodos , Recién Nacido , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Administración Oral , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Resultado del Embarazo , Administración Sublingual , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Analgésicos Opioides/administración & dosificación , Estudios de Cohortes , Adulto Joven , Combinación Buprenorfina y Naloxona/administración & dosificación , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
BACKGROUND: People who inject drugs (PWID) are at high risk for opioid overdose and infectious diseases including HIV. We piloted PARTNER UP, a telemedicine-based program to provide PWID with medication for opioid use disorder (MOUD) with buprenorphine/naloxone (bup/nx) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine through two syringe services programs (SSP) in North Carolina. We present overall results from this project, including participant retention rates and self-reported medication adherence. METHODS: Study participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly until program end at month 6. Participants were asked to start both MOUD and PrEP at initiation but could choose to discontinue either at any point during the study. Demographics and health history including substance use, sexual behaviors, and prior use of MOUD/PrEP were collected at baseline. Follow-up surveys were conducted at 3- and 6-months to assess attitudes towards MOUD and PrEP, change in opioid use and sexual behaviors, and for self-reported medication adherence. Participant retention was measured by completion of visits; provider notes were used to assess whether the participant reported continuation of medication. RESULTS: Overall, 17 persons were enrolled and started on both bup/nx and PrEP; the majority self-identified as white and male. At 3 months, 13 (76%) remained on study; 10 (77%) reported continuing with both MOUD and PrEP, 2 (15%) with bup/nx only, and 1 (8%) with PrEP only. At 6 months, 12 (71%) remained on study; 8 (67%) reported taking both bup/nx and PrEP, and 4 (33%) bup/nx only. Among survey participants, opioid use and HIV risk behaviors decreased. Nearly all reported taking bup/nx daily; however, self-reported daily adherence to PrEP was lower and declined over time. The most common reason for not continuing PrEP was feeling not at risk for acquiring HIV. CONCLUSIONS: Our study results show that MOUD and PrEP can be successfully administered via telemedicine in SSPs. PrEP appears to be a lower priority for participants with decreased continuation and adherence. Low perception of HIV risk was a reason for not continuing PrEP, possibly mitigated by MOUD use. Future studies including helping identify PWID at highest need for PrEP are needed. TRIAL REGISTRATION: Providing Suboxone and PrEP Using Telemedicine, NCT04521920. Registered 18 August 2020. https://clinicaltrials.gov/study/NCT04521920?term=mehri%20mckellar&rank=2 .
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Fármacos Anti-VIH , Infecciones por VIH , Trastornos Relacionados con Opioides , Profilaxis Pre-Exposición , Abuso de Sustancias por Vía Intravenosa , Humanos , Masculino , Fármacos Anti-VIH/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Infecciones por VIH/prevención & control , Trastornos Relacionados con Opioides/tratamiento farmacológico , Proyectos Piloto , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , FemeninoRESUMEN
INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.
Asunto(s)
Combinación Buprenorfina y Naloxona , Metadona , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Enfermedades de Transmisión Sexual , Humanos , Masculino , Metadona/uso terapéutico , Metadona/administración & dosificación , Femenino , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Canadá , Combinación Buprenorfina y Naloxona/uso terapéutico , Enfermedades de Transmisión Sexual/prevención & control , Tratamiento de Sustitución de Opiáceos/métodos , Conducta de Reducción del Riesgo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Persona de Mediana Edad , Naloxona/uso terapéutico , Buprenorfina/uso terapéuticoRESUMEN
OBJECTIVES: To describe practice patterns surrounding the use of medications to treat opioid use disorder (MOUD) in critically ill patients. DESIGN: Retrospective, multicenter, observational study using the Premier AI Healthcare Database. SETTING: The study was conducted in U.S. ICUs. PATIENTS: Adult (≥ 18 yr old) patients with a history of opioid use disorder (OUD) admitted to an ICU between 2016 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 108,189 ICU patients (658 hospitals) with a history of OUD, 20,508 patients (19.0%) received MOUD. Of patients receiving MOUD, 13,745 (67.0%) received methadone, 2,950 (14.4%) received buprenorphine, and 4,227 (20.6%) received buprenorphine/naloxone. MOUD use occurred in 37.9% of patients who received invasive mechanical ventilation. The median day of MOUD initiation was hospital day 2 (interquartile range [IQR] 1-3) and the median duration of MOUD use was 4 days (IQR 2-8). MOUD use per hospital was highly variable (median 16.0%; IQR 10-24; range, 0-70.0%); admitting hospital explained 8.9% of variation in MOUD use. A primary admitting diagnosis of unintentional poisoning (aOR 0.41; 95% CI, 0.38-0.45), presence of an additional substance use disorder (aOR 0.66; 95% CI, 0.64-0.68), and factors indicating greater severity of illness were associated with reduced odds of receiving MOUD in the ICU. CONCLUSIONS: In a large multicenter, retrospective study, there was large variation in the use of MOUD among ICU patients with a history of OUD. These results inform future studies seeking to optimize the approach to MOUD use during critical illness.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Metadona , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Metadona/uso terapéutico , Anciano , Pautas de la Práctica en Medicina/estadística & datos numéricos , Analgésicos Opioides/uso terapéutico , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Tratamiento de Sustitución de Opiáceos/métodos , Antagonistas de Narcóticos/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population-level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. DESIGN: This was a population-based time-series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy-specific guidance and the start of the COVID-19 pandemic were assessed. SETTING AND PARTICIPANTS: The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. MEASUREMENTS: We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT-exposed pregnancies among all pregnant people in Ontario. FINDINGS: Overall, rates of OAT during pregnancy have declined since mid-2018. Methadone-exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032-0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (-0.005%, 95% CI = -0.0080 to -0.0020, P = 0.001) and the start of the COVID-19 pandemic (-0.003%, 95% CI = -0.0054 to -0.0006, P = 0.015). CONCLUSION: Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018.
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COVID-19 , Metadona , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Ontario/epidemiología , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Tratamiento de Sustitución de Opiáceos/métodos , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Adulto , COVID-19/epidemiología , Buprenorfina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
AIM: How maternal opioid maintenance treatment (OMT) affects children is under-researched. This population-based registry study investigated child growth and somatic health following intrauterine exposure to this treatment. METHODS: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine-naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups. RESULTS: Of the 67 neonates, 52% were male, 96% were born full-term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years. CONCLUSION: Using child growth as the outcome, we found that buprenorphine-naloxone and buprenorphine-monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long-term follow-up of children exposed to maternal OMT.
Asunto(s)
Tratamiento de Sustitución de Opiáceos , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Tratamiento de Sustitución de Opiáceos/efectos adversos , Masculino , Recién Nacido , Factores de Riesgo , Metadona/efectos adversos , Metadona/uso terapéutico , Desarrollo Infantil/efectos de los fármacos , Adulto , Preescolar , Finlandia , Trastornos Relacionados con Opioides , Buprenorfina/efectos adversos , Buprenorfina/uso terapéutico , Lactante , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
Medications for opioid use disorder (MOUD) increase retention in care and decrease mortality during active treatment; however, information about the comparative effectiveness of different forms of MOUD is sparse. Observational comparative effectiveness studies are subject to many types of bias; a robust framework to minimize bias would improve the quality of comparative effectiveness evidence. This paper discusses the use of target trial emulation as a framework to conduct comparative effectiveness studies of MOUD with administrative data. Using examples from our planned research project comparing buprenorphine-naloxone and extended-release naltrexone with respect to the rates of MOUD discontinuation, we provide a primer on the challenges and approaches to employing target trial emulation in the study of MOUD.
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Combinación Buprenorfina y Naloxona , Investigación sobre la Eficacia Comparativa , Naltrexona , Antagonistas de Narcóticos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Naltrexona/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Buprenorfina/uso terapéutico , Estudios Observacionales como Asunto , Preparaciones de Acción Retardada , Proyectos de Investigación , Naloxona/uso terapéuticoRESUMEN
BACKGROUND/AIM: Poor medication adherence is one of the main barriers to the long-term efficacy of buprenorphine/naloxone (BUP/NAL). The aims of this pilot investigation were to examine if a Bluetooth-enabled pill cap and mobile application is a feasible, usable tool for increasing BUP/NAL adherence among people with an opioid use disorder. METHODS: This pilot randomized clinical trial (RCT; total n = 41) lasted 12 weeks and was conducted in two office-based BUP/NAL provider locations in Spokane, WA and Coeur d'Alene, ID from January 2020 to September of 2021 with an 11-month gap due to COVID-19. Patients receiving BUP/NAL who consented to participate were randomized to receive the pill cap device (PLY group; n = 19) or a service as usual (SAU group; n = 22) group that included an identical but inactive cap for their bottle. The PLY group received reminders via text and voice, and the support of a "helper" (e.g., friend) to monitor pill cap openings. RESULTS: Most participants in PLY group found the device both feasible (92.86 %) and usable (78.57 %). Most participants liked using the device (92.86 %) and were satisfied with the device (85.71 %). While not statistically different from one another, medication adherence per the Medication Possession Ratio was 75 % in the SAU group and 84 % in the PLY group. Pill cap openings were significantly higher in the PLY group with an average of 91.8 openings versus the SAU group's average of 56.7 (p < 0.05). CONCLUSION: The devices was feasible, usable, and patients had high levels of satisfaction. The device was associated with increased pill openings.