RESUMEN
Transitioning a patient with chronic pain from a fentanyl patch to a buprenorphine patch has not been well described in the literature. Even after a patient removes their fentanyl patch, the residual fentanyl in the skin continues to be absorbed for hours. Due to the risk of precipitated withdrawal when initiating buprenorphine, this transition is a more challenging opioid rotation to plan safely. We report a case of a patient who had been using a fentanyl patch for over 10 years and was successfully rotated directly to a buprenorphine patch.
Asunto(s)
Analgésicos Opioides , Buprenorfina , Dolor Crónico , Fentanilo , Parche Transdérmico , Humanos , Buprenorfina/administración & dosificación , Buprenorfina/efectos adversos , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Dolor Crónico/tratamiento farmacológico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Administración Cutánea , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Tratamiento de Sustitución de Opiáceos , FemeninoRESUMEN
OBJECTIVE: To determine if the agonistic effects of buprenorphine and methadone affect drug use. METHOD: Quantitative examination of urine drug concentrations of patients treated with buprenorphine and methadone. RESULTS: Patients on buprenorphine had less opioid and methamphetamine drug use than those on methadone. CONCLUSION: Patients on buprenorphine therapy appear to use less illicit drugs.
Asunto(s)
Buprenorfina , Metadona , Tratamiento de Sustitución de Opiáceos , Humanos , Buprenorfina/uso terapéutico , Buprenorfina/efectos adversos , Metadona/uso terapéutico , Trastornos Relacionados con Opioides/orina , Trastornos Relacionados con Opioides/tratamiento farmacológico , Drogas Ilícitas/orina , Drogas Ilícitas/efectos adversos , Detección de Abuso de Sustancias , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/efectos adversos , Masculino , Adulto , Femenino , Uso Recreativo de DrogasRESUMEN
Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.
Asunto(s)
Analgésicos Opioides , Buprenorfina , Dolor Crónico , Dolor de la Región Lumbar , Humanos , Buprenorfina/efectos adversos , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Estudios Retrospectivos , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Femenino , Masculino , Dolor de la Región Lumbar/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Dolor Crónico/tratamiento farmacológico , Administración Oral , Revisión de Utilización de Seguros/estadística & datos numéricos , Parche Transdérmico , Adulto Joven , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
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
Extended-release formulations of buprenorphine offer less frequent dosing, provide consistent medication delivery, and improve adherence for treatment of opioid use disorder (OUD). Although buprenorphine is a partial agonist with seemingly less precipitated withdrawal and easier initiation than full opioid agonists used for OUD, its use is not benign and understanding of the different extended-release formulations is necessary. We report a case of a patient that received a long-acting buprenorphine formulation (Sublocade®) administered subcutaneously that presented to the emergency department with tachycardia, hyperglycemia, elevated anion gap, and sustained nausea and vomiting refractory to pharmacotherapy requiring surgical removal of the buprenorphine depot for resolution of nausea and vomiting symptoms.
Asunto(s)
Buprenorfina , Preparaciones de Acción Retardada , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/administración & dosificación , Buprenorfina/efectos adversos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Masculino , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Adulto , Femenino , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/tratamiento farmacológicoRESUMEN
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
OBJECTIVE: The aim of the study is to review and synthesize the literature on high-dose buprenorphine initiation (>12-mg total dose on day of initiation). METHODS: A scoping review of literature about high-dose buprenorphine initiation was conducted. MEDLINE, Embase, PsycINFO, and Cochrane Central were searched. Randomized controlled trials, prospective and retrospective cohort studies, and case studies/reports published in English before February 13, 2023, were included. RESULTS: Fifteen studies reporting outcomes from 580 high-dose buprenorphine initiations were included. Eight studies were in inpatient settings, 3 in emergency departments, 3 in outpatient settings, and 1 in a first-responder setting. Four studies reported high-dose initiations among individuals exposed to fentanyl. There were no reported events of fatal or nonfatal overdose or respiratory depression, although adverse event reporting was inconsistent in published reports. The most reported side effects with high-dose buprenorphine initiation were nausea or vomiting (n = 17) and precipitated withdrawal (n = 7). The most serious reported adverse event was hypotension requiring oral hydration (n = 2). Most studies reported improvements in subjective or objective withdrawal symptoms. The duration of follow-up ranged from none to 8 months. CONCLUSIONS: High-dose buprenorphine initiation has not been associated with reported cases of overdose or respiratory depression. However, the current literature about high-dose buprenorphine is limited by inconsistent side effect reporting, limited power to detect rare safety events such as respiratory depression, limited follow-up data, and few comparison studies between high-dose and regular initiation protocols. Further prospective data are needed to evaluate the safety and effectiveness of this initiation strategy.
Asunto(s)
Buprenorfina , Humanos , Buprenorfina/administración & dosificación , Buprenorfina/efectos adversos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Antagonistas de Narcóticos/administración & dosificación , Síndrome de Abstinencia a Sustancias , Tratamiento de Sustitución de Opiáceos/métodos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversosRESUMEN
PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.
Asunto(s)
Analgésicos Opioides , COVID-19 , Epidemia de Opioides , Trastornos Relacionados con Opioides , Manejo del Dolor , Dolor Postoperatorio , Atención Perioperativa , Humanos , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/etiología , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/diagnóstico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Epidemia de Opioides/prevención & control , Manejo del Dolor/métodos , Manejo del Dolor/efectos adversos , COVID-19/epidemiología , COVID-19/prevención & control , Atención Perioperativa/métodos , Atención Perioperativa/normas , Buprenorfina/uso terapéutico , Buprenorfina/efectos adversos , Recuperación Mejorada Después de la CirugíaRESUMEN
PURPOSE: Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk. METHODS: Eight healthy adult cats were evaluated to determine changes in airway protection status and for evidence of dysphagia in two experiments. (1) In four female cats, airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015 mg/kg, IM, q8-12 h; n = 5). (2) Using a cross-over design, four naive cats (2 male, 2 female) were treated with moderate-dose (0.02 mg/kg) or high-dose (0.04 mg/kg) buprenorphine (IM, q8-12 h; n = 5). RESULTS: Airway protection was significantly affected in both experiments, but the most severe deficits occurred post-surgically as 75% of the animals exhibited silent aspiration. CONCLUSION: Oropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the postoperative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.
Asunto(s)
Analgésicos Opioides , Enfermedades de los Gatos , Trastornos de Deglución , Neumonía , Animales , Gatos , Femenino , Masculino , Analgésicos Opioides/efectos adversos , Buprenorfina/efectos adversos , Enfermedades de los Gatos/inducido químicamente , Trastornos de Deglución/etiología , Trastornos de Deglución/veterinaria , Neumonía/inducido químicamente , Neumonía/complicaciones , Neumonía/veterinaria , Estudios CruzadosRESUMEN
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
BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.
Asunto(s)
Buprenorfina , Naltrexona/análogos & derivados , Trastornos Relacionados con Opioides , Síndrome de Abstinencia a Sustancias , Femenino , Animales , Bovinos , Humanos , Adulto , Olanzapina/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Buprenorfina/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/etiología , Difenhidramina , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
INTRODUCTION: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4) as an NMDA receptor antagonist on OWS. MATERIALS AND METHODS: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later. RESULTS: Both groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group. CONCLUSION: Magnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results.
Asunto(s)
Buprenorfina , Sulfato de Magnesio , Síndrome de Abstinencia a Sustancias , Humanos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Buprenorfina/efectos adversos , Masculino , Adulto , Femenino , Método Doble Ciego , Sulfato de Magnesio/administración & dosificación , Sulfato de Magnesio/uso terapéutico , Sulfato de Magnesio/farmacología , Sulfato de Magnesio/efectos adversos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Persona de Mediana Edad , Clonidina/administración & dosificación , Clonidina/uso terapéutico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Quimioterapia Combinada , Irán , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Acetaminofén/efectos adversos , Diazepam/uso terapéutico , Diazepam/administración & dosificación , Diazepam/efectos adversos , Diazepam/farmacología , Adulto JovenRESUMEN
Hypogonadism is a highly prevalent complication of chronic opioid use associated with a constellation of affective, algesic, and cognitive symptoms as well as decreased quality of life. Given that the mainstays of pharmacologic opioid use disorder (OUD) treatment - methadone and buprenorphine - are themselves agonists or partial agonists at the mu opioid receptor, opioid-induced hypogonadism (OIH) remains an underappreciated clinical concern throughout the course of OUD treatment. Prominent theoretical frameworks for OUD emphasize the importance of negative reinforcement and hyperkatifeia, defined as the heightened salience of negative emotional and motivational states brought on by chronic opioid use. In this perspective article, we highlight the striking parallels between the symptom domains of hyperfakifeia and hypogonadism in males, who comprise the vast majority of existing clinical research on OIH. By extension we propose that future research and ultimately clinical care should focus on the identification and treatment of OIH in OUD patients to help address the longstanding paradox of poor treatment retention despite efficacious therapies, particularly in the setting of the current opioid overdose epidemic driven by high potency synthetic opioids such as fentanyl. We then review evidence from chronic pain patients that testosterone replacement provides clinically significant benefits to men with OIH. Finally, using this framework, we compare extant OUD therapeutics and discuss critical gaps in the clinical literature-including the relative dearth of data regarding hypothalamic-pituitary-gonadal function in females who use opioids-where future study should be focused.
Asunto(s)
Analgésicos Opioides , Hipogonadismo , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Buprenorfina/uso terapéutico , Buprenorfina/efectos adversos , Hipogonadismo/inducido químicamente , Hipogonadismo/tratamiento farmacológico , Metadona/uso terapéutico , Metadona/efectos adversos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Refuerzo en PsicologíaRESUMEN
BACKGROUND: There is currently a clinical dilemma in treating acute pain in patients receiving long-term buprenorphine products. METHODS: This is a retrospective cohort review involving patients receiving long-term buprenorphine therapy who either underwent a surgical procedure or presented to an emergency department (ED) for acute pain between January 1, 2012 and January 1, 2022. Patients were excluded if opioids were prescribed 30 days before the index date. Chart reviews were conducted to characterize buprenorphine treatment strategies and the addition of new pain medications. Chart review revealed (1) incidence of opioid use disorder (OUD) relapse, (2) hospital re-presentation for pain or OUD, (3) fatal and non-fatal overdose, and (4) all-cause mortality and suicidality. Descriptive statistics were used to analyze results. RESULTS: A total of 70 of 259 screened patients met inclusion criteria. The mean (±SD) age was 50.3 ± 13 years, 92.9% male, 64.3% White, and 78.6% had an OUD diagnosis. While 84.3% presented to the ED, 15.7% underwent surgical procedures. For the primary endpoint, the total daily dose of buprenorphine or buprenorphine/naloxone from index date to discharge was continued in 90.0%, increased in 2.9%, decreased in 1.4%, and discontinued in 5.7% of cases. At discharge, 46.2% were prescribed an additional pain medication. A total of 7.1% re-presented for pain or OUD relapse, 15.7% experienced an OUD relapse, 1.4% experienced new-onset suicidality, and 1.4% experience all-cause mortality within 90 days of the index date. No fatal or non-fatal opioid overdoses were observed. CONCLUSION: The most commonly observed practice was continuing buprenorphine doses in patients with acute or postsurgical pain, which was effective and safe. Although further data is necessary to fully elucidate these findings, the data herein may suggest that clinicians can safely continue buprenorphine doses in the acute pain setting in patients receiving these products chronically.
Asunto(s)
Dolor Agudo , Analgésicos Opioides , Combinación Buprenorfina y Naloxona , Buprenorfina , Trastornos Relacionados con Opioides , Manejo del Dolor , Dolor Postoperatorio , Humanos , Masculino , Femenino , Estudios Retrospectivos , Dolor Postoperatorio/tratamiento farmacológico , Persona de Mediana Edad , Trastornos Relacionados con Opioides/tratamiento farmacológico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Adulto , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Buprenorfina/efectos adversos , Dolor Agudo/tratamiento farmacológico , Combinación Buprenorfina y Naloxona/uso terapéutico , Combinación Buprenorfina y Naloxona/administración & dosificación , Manejo del Dolor/métodos , Anciano , Sobredosis de Droga , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We tested the effects of the clinically relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated the utility of 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague-Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus, and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing. We evaluated the hypotheses that swallowing varies by stimulus, opioids depress swallowing and breathing, and that 5-HT1A agonists improve these depressions. Our results largely confirmed the following hypotheses: 1) swallow-related EMG activity was larger during swallows elicited by esophageal distension plus oral water infusion than by either stimulus alone. 2) Buprenorphine depressed swallow in both sexes, but females were more susceptible to total swallow suppression. 3) Female animals were also more vulnerable to opioid-induced respiratory depression. 4) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pretreatment with the partial 5-HT1A agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. 5) 8-OH-DPAT enhanced mylohyoid and thyropharyngeus EMG amplitude during swallow but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide preclinical evidence of a 5HT1A agonist for the treatment of respiratory depression and dysphagia.NEW & NOTEWORTHY This is the first study, to our knowledge, to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females compared with males, and we are the first to produce this effect with the partial µ-opioid-receptor agonist buprenorphine. This is the first demonstration, to our knowledge, that activation of 5-HT1A receptors can improve swallow and breathing outcomes following systemic buprenorphine administration.
Asunto(s)
Buprenorfina , Trastornos de Deglución , Insuficiencia Respiratoria , Ratas , Femenino , Masculino , Animales , Analgésicos Opioides/farmacología , Serotonina , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/uso terapéutico , Buspirona/efectos adversos , Ratas Sprague-Dawley , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/tratamiento farmacológico , Buprenorfina/efectos adversosRESUMEN
BACKGROUND: Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. METHODS: We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. RESULTS: Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. CONCLUSION: Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.
Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/efectos adversos , Naloxona/uso terapéutico , Analgésicos Opioides/efectos adversos , Estudios Prospectivos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/psicología , Tratamiento de Sustitución de Opiáceos , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
ABSTRACT: Monthly long-acting injectable buprenorphine (LAI-BUP) is a treatment option for moderate to severe opioid use disorder. Safe administration of LAI-BUP requires preexisting opioid tolerance to prevent sedation and respiratory depression. In the event of adverse medication effects including oversedation, LAI-BUP can be surgically excised up to 14 days after administration ( https://www.sublocadehcp.com/dosing-administration ). However, the manufacturer does not provide guidance on the proper procedure for excision, and no case reports have been published documenting this procedure. We report a case of a man with methamphetamine use disorder and multiple unintentional fentanyl overdoses who inadvertently received LAI-BUP for overdose protection. This resulted in significant sedation for days, ultimately necessitating excision 5 days after administration. His sedation improved moderately at 24 hours after excision and significantly by 36 hours after excision. Providers seeking to use LAI-BUP to prevent overdose among those with unintentional opioid exposure must ensure sublingual buprenorphine tolerance before injection to avoid iatrogenic harm. Although manufacturer instructions mention that LAI-BUP can be excised under local anesthesia within 14 days of insertion, ideal excision is best performed in a setting with surgical instruments and cautery-such as the operating room-as the depot can adhere strongly to the surrounding subcutaneous tissue.
Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Masculino , Administración Sublingual , Analgésicos Opioides/efectos adversos , Buprenorfina/efectos adversos , Tolerancia a Medicamentos , Antagonistas de Narcóticos/efectos adversos , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
Importance: Use of buprenorphine or methadone to treat opioid use disorder is recommended in pregnancy; however, their teratogenic potential is largely unknown. Objective: To compare the risk of congenital malformations following in utero exposure to buprenorphine vs methadone. Design, Setting, and Participants: This population-based cohort study used health care utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. A total of 13â¯360 pregnancies with enrollment from 90 days prior to pregnancy start through 1 month after delivery and first trimester use of buprenorphine or methadone were included and linked to infants. Data were analyzed from July to December 2022. Exposure: A pharmacy dispensing of buprenorphine or a code for administration of methadone in the first trimester. Main Outcomes and Measures: Primary outcomes included major malformations overall and malformations previously associated with opioids (any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, clubfoot, and oral clefts). Secondary outcomes included other organ system-specific malformations. Risk differences and risk ratios (RRs) were estimated comparing buprenorphine with methadone, adjusting for confounders with propensity score overlap weights. Results: The cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean [SD] maternal age, 28.4 [4.6] years) and 3846 with methadone exposure (mean [SD] maternal age, 28.8 [4.7] years). The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone. After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). Risk was lower with buprenorphine for cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), including both ventricular septal defect (RR, 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defect/nonprematurity-related patent foramen ovale (RR, 0.54; 95% CI, 0.30-0.97), oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and clubfoot (RR, 0.55; 95% CI, 0.32-0.94). Results for neural tube defects were uncertain given low event counts. In secondary analyses, buprenorphine was associated with a decreased risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses. Conclusions and Relevance: In this cohort study, the risk of most malformations previously associated with opioid exposure was lower in buprenorphine-exposed infants compared with methadone-exposed infants, independent of measured confounders. Malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.
Asunto(s)
Buprenorfina , Pie Equinovaro , Foramen Oval Permeable , Cardiopatías Congénitas , Defectos del Tabique Interventricular , Defectos del Tubo Neural , Trastornos Relacionados con Opioides , Complicaciones del Embarazo , Embarazo , Lactante , Femenino , Humanos , Adulto , Metadona/efectos adversos , Buprenorfina/efectos adversos , Primer Trimestre del Embarazo , Estudios de Cohortes , Pie Equinovaro/complicaciones , Pie Equinovaro/tratamiento farmacológico , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Cardiopatías Congénitas/inducido químicamente , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/complicaciones , Defectos del Tubo Neural/complicaciones , Defectos del Tubo Neural/tratamiento farmacológico , Defectos del Tabique Interventricular/complicaciones , Defectos del Tabique Interventricular/tratamiento farmacológicoAsunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Embarazo , Femenino , Humanos , Metadona/efectos adversos , Buprenorfina/efectos adversos , Analgésicos Opioides/efectos adversos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/rehabilitaciónRESUMEN
BACKGROUND AND OBJECTIVES: The relative safety and efficacy of monthly extended-release buprenorphine (XR-BUP) has not been fully evaluated in pregnant persons. METHODS: Case report of two pregnant individuals receiving XR-BUP while pregnant. RESULTS: Both patients had positive experiences and healthy infants. DISCUSSION AND CONCLUSIONS: Sparse data regarding the use of XR-BUP in pregnant patients limits shared decision-making. Additional evidence will support the growing population of pregnant patients exposed to XR-BUP. SCIENTIFIC SIGNIFICANCE: Positive patient experiences using XR-BUP during pregnancy have been previously unreported. This report will contribute to discussions of risks and benefits for future patients using XR-BUP during pregnancy.