The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

Maternal Perspective of Inpatient Methadone Initiation: Opportunities to Increase Retention in Treatment.

OBJECTIVES: Recent trends demonstrate increases in the rates of opioid use among pregnant and parenting women. Treatment for pregnant people with opioid use disorder (OUD) includes medications for OUD, like methadone, as well as comprehensive support services. Still, inpatient treatment engagement is suboptimal and treatment drop out is common. There is little research examining the maternal perspective of the inpatient methadone initiation experience. The primary aim of this qualitative methods study was to explore patient experience and perspective of the inpatient methadone initiation period. METHODS: All participants were recruited from a single urban university affiliated hospital and OUD treatment program. Data were collected from 30 maternal participants in OUD treatment about their inpatient methadone initiation experience while pregnant using semistructured interviews. Thematic analyses were conducted using an inductive approach after an iterative process of code development and application among a multidisciplinary team of 3 coders. Validity was accounted for through 2 participant feedback interviews and study team review and discussion of findings. RESULTS: Four themes emerged from the maternal interview data: (1) Barriers to Inpatient Methadone Initiation, (2) Facilitators to Inpatient Methadone Initiation, (3) Transition From Hospital Inpatient to Outpatient or Residential OUD Treatment Services, and (4) Opportunities for Enhanced Clinical Support. CONCLUSION: Maternal participants reported multiple barriers and facilitators to inpatient care during methadone initiation, highlighting opportunities for improvement to effectively engage pregnant individuals in treatment.

A practical guide for buprenorphine initiation in the primary care setting.

Buprenorphine is a safe and effective treatment for opioid use disorder but remains underutilized because a major challenge of conventional buprenorphine initiation (termed induction) is that the patient must already be in opioid withdrawal. Previous legal barriers and clinician lack of familiarity with the unique pharmacology of buprenorphine have also limited its use. In this review, we outline changes regarding buprenorphine prescribing laws and physician perceptions of buprenorphine. We also review buprenorphine pharmacology and novel low-dose buprenorphine induction procedures that can be adopted in primary care settings to improve treatment acceptability, retention, and outcomes.

Prescription amphetamines in people with opioid use disorder and co-occurring psychostimulant use disorder initiating buprenorphine: an analysis of treatment retention and overdose risk.

BACKGROUND: Attention-deficit and hyperactivity disorder (ADHD) is frequently diagnosed in patients with substance use disorders (SUDs), including opioids. There remains concern about the safety and efficacy of prescription amphetamines (PAs) and their impact on effectiveness of opioid use disorder (OUD) treatment with buprenorphine. OBJECTIVES: To assess the effect of PAs on OUD buprenorphine treatment retention and/or SUD-related emergency admission or drug-related poisonings. METHODS: We used a retrospective cohort design with a secondary analysis of data from Merative MarketScan Commercial and Multi-State Medicaid Databases from 1 January 2006 to 31 December 2016. Individuals included were aged 12-64 years, had an OUD diagnosis and were prescribed buprenorphine. Our analysis used multivariable Cox regression to evaluate the relationship between PA receipt and time to buprenorphine discontinuation. The second part focused on subsamples of buprenorphine initiators who had either (1) any SUD-related emergency admissions or (2) drug-related poisoning. These outcomes were modelled as a function of PA exposure using conditional logistic regression models as part of a within-person, case-crossover design. FINDINGS: Our sample had 90 269 patients with OUD (mean age 34.2 years (SD=11.3)) who initiated buprenorphine. Being prescribed a PA was associated with improved buprenorphine retention among individuals both with (adjusted HR (aHR) 0.91 (95% CI 0.86 to 0.97)) and without a concurrent psychostimulant use disorder (PSUD) (aHR 0.92 (95% CI 0.90 to 0.93)). CONCLUSIONS: PA use was associated with improved buprenorphine retention in people with OUD with and without co-occurring PSUD. The risks of acute SUD-related events and drug-related poisonings associated with PA use did not differ when comparing PA-using days with days without PA use. CLINICAL IMPLICATIONS: Patients with OUD on buprenorphine should receive treatment with a PA when indicated.

Antipanic-like effect of esketamine and buprenorphine in rats exposed to acute hypoxia.

The antidepressant effect of ketamine has been widely acknowledged and the use of one of its enantiomers, S-ketamine (esketamine), has recently been approved for the clinical management of treatment-resistant depression. As with ketamine, the non-selective opioid receptor-interacting drug buprenorphine is reported to have antidepressant and anxiolytic properties in humans and rodents. Given the fact that antidepressant drugs are also first line treatment for panic disorder, it is surprising that the potential panicolytic effect of these compounds has been scarcely (ketamine), or not yet (buprenorphine) investigated. We here evaluated the effects of ketamine (the racemic mixture), esketamine, and buprenorphine in male Wistar rats submitted to a panicogenic challenge: acute exposure to hypoxia (7% O2). We observed that esketamine (20 mg/kg), but not ketamine, decreased the number of escape attempts made during hypoxia, and this effect could be observed even 7 days after the drug administration. A panicolytic-like effect was also observed with MK801, which like esketamine, antagonizes NMDA glutamate receptors. Buprenorphine (0.3 mg/kg) also impaired hypoxia-induced escape, an effect blocked by the non-selective opioid receptor antagonist naloxone, indicating an interaction with classical ligand sites, such as µ and kappa receptors, but not with nociception/orphanin FQ receptors. Altogether, the results suggest that esketamine and buprenorphine cause rapid-onset panicolytic-like effects, and may be alternatives for treating panic disorder, particularly in patients who are refractory to standard pharmacological treatment.

Opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica / Strong opioids (fentanyl, oxycodone and buprenorphine) for the treatment of chronic pain

INTRODUÇÃO: Considera-se que, no Brasil, a dor crônica seja umas das principais razões de atendimento ambulatorial da dor. A dor crônica pode estar associada a diferentes agravos e ter um ou vários componentes. Considera-se que a percepção da dor é diferente para pacientes com a mesma doença, variando em sofrimento de acordo com sexo, raça, cultura, e história pessoal. Quatro grandes grupos serão abordados no presente relatório, a saber, dor crônica oncológica, musculoesquelética (dor de osteoartrite, dor lombar), neuropática e dor não oncológica ou não específica. Os opioides continuam sendo o padrão ouro pelo qual os outros analgésicos clinicamente efetivos são medidos. Para a dor moderada a grave, os opioides fortes podem ser considerados primeira linha. Os opioides fortes padronizados pela Relação Nacional de Medicamentos Essenciais (RENAME) são a morfina e a metadona. Os especialistas presentes na reunião de escopo da atualização do PCDT da Dor Crônica propuseram a avaliação dos medicamentos fentanila, oxicodona e buprenorfina. TECNOLOGIA: Opioides fortes (fentanila, oxicodona e buprenorfina). PERGUNTA: Os opioides fortes (fentanila, oxicodona e buprenorfina) são eficazes, seguros e custo-efetivos no tratamento de pacientes adultos com dor crônica, quando comparados aos medicamentos atualmente disponíveis no SUS para esta indicação? EVIDÊNCIAS CLÍNICAS: Por meio da pergunta PICO, foram realizadas buscas nas plataformas Medline (PUBMED) e EMBASE. Foram encontradas 8.873 publicações e, ao final, foram incl

Opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica / Strong opioids (fentanyl, oxycodone and buprenorphine) for the treatment of chronic pain

O QUE É DOR CRÔNICA?: A dor crônica é aquela que persiste por um período igual ou superior a três meses. No Brasil, de todas as pessoas que buscam atendimento ambulatorial por causa de dor, entre 28% e 76% se referem a quadros de dor crônica. Essa dor acaba trazendo não apenas sofrimento físico, mas também psicológico, podendo comprometer a qualidade de vida, gerar incapacitação, ansiedade e depressão. COMO OS PACIENTES COM DOR CRÔNICA SÃO TRATADOS NO SUS? O PCDT (Protocolo Clínico e Diretrizes Terapêuticas) da Dor Crônica, publicado em 2012, indica o tratamento farmacológico para os diferentes tipos de dores de acordo com uma escala em degraus numéricos, que correspondem a uma determinada combinação de medicamentos. MEDICAMENTOS ANALISADOS: OPIOIDES FORTES (FENTANILA, OXICODONA E BUPRENORFINA): Os opioides são substâncias químicas que atuam em uma área do cérebro chamada sistema nervoso central e possuem potentes propriedades analgésicas. Os opioides fortes atualmente disponíveis no SUS são a morfina e a metadona. Motivada pela atualização do PCDT da Dor Crônica, a Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde, do Ministério da Saúde (SCTIE/MS), demandou a incorporação dos opioides fortes fentanila, oxicodona e buprenorfina para o tratamento de pacientes com dor crônica no Sistema Único de Saúde (SUS). PERSPECTIVA DO PACIENTE: As chamadas públicas para participar da Perspectiva do Paciente sobre os temas de dor crônica foram abertas em dois períodos distintos: de 13/01/2021 a 17/01/2021 e de 19/01/2021 a 02/02/2021. As quatro chamadas públicas abertas tiveram um total de 32 inscrições. A indicação dos representantes titular e suplente foi feita a partir de consenso entre o grupo de inscritos. RECOMENDAÇÃO INICIAL DA CONITEC: A Conitec recomendou inicialmente a não incorporação dos opioides fortes fentanila, oxicodona e buprenorfina no SUS para o tratamento de dor crônica. Esse tema foi discutido durante a 97ª reunião ordinária da Comissão, realizada nos dias 05 e 06 de maio de 2021. Na ocasião, o Plenário considerou que os resultados das análises não mostraram diferença significante entre os medicamentos mencionados e aqueles disponíveis atualmente no SUS, seja em termos de eficácia ou de segurança. O assunto esteve disponível na consulta pública nº 44, durante 20 dias, no período de 27/05/2021 a 15/06/2021, para receber contribuições da sociedade (opiniões, sugestões e críticas) sobre o tema. RESULTADO DA CONSULTA PÚBLICA: Foram recebidas 65 contribuições, sendo 30 de natureza técnico-científica e 35 de experiência ou opinião. As contribuições abordaram principalmente a necessidade de incorporação dos opióides fortes para dor oncológica. Os resultados da consulta pública, no entanto, não foram suficientes para alterar o entendimento do plenário e a recomendação inicial, desfavorável à incorporação, foi mantida. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 99ª Reunião Ordinária, no dia 01 de julho de 2021, deliberou por unanimidade recomendar a não incorporação dos opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica, pois entendeu que as contribuições da consulta pública não trouxeram elementos suficientes para promover a mudança da recomendação preliminar, que ficou mantida. DECISÃO FINAL: Com base na recomendação da Conitec, o secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde, no uso de suas atribuições legais, decidiu pela não incorporação, no âmbito do Sistema Único de Saúde - SUS, dos opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica.

Designing and Evaluating COVID-19 Protocols for an Office-Based Opioid Treatment Program in an Urban Underserved Setting.

BACKGROUND: Despite changing federal regulations for providing telehealth services and provision of controlled substances during the COVID-19 pandemic, there is little guidance available for office-based opioid treatment (OBOT) programs integrated into primary care settings. PURPOSE: (1) Develop disaster-preparedness protocols specific to the COVID-19 pandemic for an urban OBOT program, and (2) evaluate the impacts of the protocol and telehealth on care. METHODS: Disaster-preparedness protocols specific to the COVID-19 pandemic were developed for an urban OBOT program, implemented on March 16, 2020. Retrospective chart review compared patients from January 1, 2020 to March 13, 2020, to patients from March 16, 2020 to April 30, 2020, abstracting patient demographics and comparing show and no-show rates between studied groups. RESULTS: The disaster-preparedness protocol was developed under a deliberative process to address social issues of the urban underserved population. Of 852 visits conducted between Jan 1, 2020, and April 30, 2020, a 91.7% show rate (n = 166/181) was documented for telemedicine visits after protocol implementation compared with a 74.1% show rate (n = 497/671) for routine in-person care (P = .06) without significant differences between the study populations. The no-show rate was significantly lower after protocol implementation (8.3% vs 25.9%; P <0.05). CONCLUSIONS: OBOTs require organized workflows to continue to provide services during the COVID-19 pandemic. Telemedicine, in the face of relaxed federal regulations, has the opportunity to enhance addiction care, creating a more convenient as well as an equally effective mechanism for OBOTs to deliver care that should inform future policy.

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

Socially distant and out of reach: Unintended consequences of COVID-19 prevention efforts on transgender and gender non-binary populations in Puerto Rico.

Substance use disorders in the United States disproportionately affect minorities and socially vulnerable populations, particularly those at the intersection of racial and sexual minority status. Preceded by over a century-long subjugation to the U.S. government, a recent financial crisis, the devastating hurricanes of 2017, and a string of earthquakes at the end of 2019 and early 2020, the current COVID-19 pandemic is only the most recent disaster to disrupt the local health care system in Puerto Rico. However, the effects of the current emergency and imposed social distancing measures have only exacerbated the underlying vulnerabilities of the transgender and gender non-conforming (GNC) population made bare during these other recent disasters. Clinics and providers who treat patients with opioid use disorder (OUD) in Puerto Rico have had to develop their own safety protocols to limit the spread of the virus while trying to optimize current treatment protocols to maintain the stability of their patients. Despite these measures, we have observed a reduction in the ability of local organizations to outreach to already disconnected transgender and GNC individuals with OUD. For example, due to the government-imposed curfew that began March 15, 2020, some providers engaged in outreach with transgender and GNC sex workers have eliminated nighttime outreach completely. Additionally, a research project surveying all buprenorphine prescribers in Puerto Rico has found that few have received training in treating this vulnerable population, and even fewer report that they are currently providing treatment for transgender or GNC individuals. If Puerto Rico is to address this problem of gross under-representation of a population known to be disproportionately affected by substance use disorders, Puerto Rico must address structural factors to prevent this disparity from widening further during the inevitable future disasters our health care system will face.

Analysis of psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in Medicare Part D in the United States.

INTRODUCTION: The opioid epidemic is a severe problem in the world, especially in the United States, where prescription opioid overdose accounts for a quarter of drug overdose deaths. OBJECTIVE: To describe psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in the United States. METHODS: We conducted a retrospective cross-sectional study of the 2016 Medicare Part D claims data and analyzed psychiatrists' prescriptions of: 1) opioids; 2) benzodiazepines, whose concurrent prescription with opioids can cause overdose death; 3) buprenorphine, a partial opioid agonist for treating opioid addiction; 4) and naltrexone microsphere, a once-monthly injectable opioid antagonist to prevent relapse to opioid dependence. Prescribers with 11 or more claims were included in the analysis. RESULTS: In Medicare Part D in 2016, there were a total of 1,131,550 prescribers accounting for 1,480,972,766 total prescriptions and 78,145,305 opioid prescriptions, including 25,528 psychiatrists (2.6% of all prescribers) accounting for 44,684,504 total prescriptions (3.0% of all prescriptions) and 131,115 opioid prescriptions (0.2% of all opioid prescriptions). Psychiatrists accounted for 17.3% of benzodiazepine, 16.3% of buprenorphine, and 33.4% of naltrexone microsphere prescriptions. The opioid prescription rate of psychiatrists was much lower than that of all prescribers (0.3 vs 5.3%). The buprenorphine prescription rate of psychiatrists was much higher than that of all prescribers (2.3 vs. 0.1%). There was a substantial geographical variation across the United States. CONCLUSIONS: The results show that, proportionally, psychiatrists have lower rates of opioid prescription and higher rates of benzodiazepine and buprenorphine prescription.

Analysis of psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in Medicare Part D in the United States

Abstract Introduction The opioid epidemic is a severe problem in the world, especially in the United States, where prescription opioid overdose accounts for a quarter of drug overdose deaths. Objective To describe psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in the United States. Methods We conducted a retrospective cross-sectional study of the 2016 Medicare Part D claims data and analyzed psychiatrists' prescriptions of: 1) opioids; 2) benzodiazepines, whose concurrent prescription with opioids can cause overdose death; 3) buprenorphine, a partial opioid agonist for treating opioid addiction; 4) and naltrexone microsphere, a once-monthly injectable opioid antagonist to prevent relapse to opioid dependence. Prescribers with 11 or more claims were included in the analysis. Results In Medicare Part D in 2016, there were a total of 1,131,550 prescribers accounting for 1,480,972,766 total prescriptions and 78,145,305 opioid prescriptions, including 25,528 psychiatrists (2.6% of all prescribers) accounting for 44,684,504 total prescriptions (3.0% of all prescriptions) and 131,115 opioid prescriptions (0.2% of all opioid prescriptions). Psychiatrists accounted for 17.3% of benzodiazepine, 16.3% of buprenorphine, and 33.4% of naltrexone microsphere prescriptions. The opioid prescription rate of psychiatrists was much lower than that of all prescribers (0.3 vs 5.3%). The buprenorphine prescription rate of psychiatrists was much higher than that of all prescribers (2.3 vs. 0.1%). There was a substantial geographical variation across the United States. Conclusions The results show that, proportionally, psychiatrists have lower rates of opioid prescription and higher rates of benzodiazepine and buprenorphine prescription.

[Treatment of borderline personality disorder with opioid antagonists: buprenorphine, nalmefene, naloxone and naltrexone in the treatment of dissociative symptoms, self-mutilation and suicidal behavior]. / Tratamiento del Trastorno límite de la personalidad con antagonistas opioides: buprenorfina, nalmefeno, naloxona y naltrexona en el tratamiento de síntomas disociativos, automutilaciones y conducta suicida.

OBJECTIVE: Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients. METHOD: We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures. RESULTS: A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria. CONCLUSIONS: Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions.

The Role of Preterm Birth in the Association Between Opioid Maintenance Therapy and Neonatal Abstinence Syndrome.

BACKGROUND: Pregnant women treated with methadone as opioid maintenance therapy are more likely than women treated with buprenorphine to deliver preterm. Preterm birth is associated with less risk of neonatal abstinence syndrome (NAS). We sought to assess the role of preterm birth as a mediator of the relationship between in utero exposure to methadone and NAS compared with buprenorphine. METHODS: We studied 716 women receiving methadone or buprenorphine and delivering liveborn infants at Magee-Womens Hospital, Pittsburgh, Pennsylvania (2013-15). We implemented inverse probability weighted marginal structural models to isolate the role of preterm birth (<37 weeks' gestation). Weights accounted for confounding by maternal age, race, insurance, parity, delivery year, marital, employment, hepatitis C, and smoking status. RESULTS: Approximately 57% of the cohort were treated with methadone. Preterm birth was more common in methadone-exposed pregnancies (25% versus 14%). The incidence of NAS treatment was higher in methadone compared with buprenorphine-exposed infants (65% vs 49%), and term compared with preterm births (64% vs 36%). For every 100 infants liveborn to mothers treated for opioid dependence, there were 13 excess cases of NAS among infants exposed to methadone compared with buprenorphine (adjusted risk difference [RD] 13.3, 95% confidence interval [CI] 5.7, 20.9). Among term births, this increased to 17 excess cases of NAS in methadone- compared with buprenorphine-exposed (RD 16.7, 95% CI 9.3, 24.0). CONCLUSION: The further increased risk of NAS associated with methadone use vs buprenorphine in term deliveries emphasises the utility of buprenorphine in clinical settings aimed at decreasing NAS.

Eficacia y seguridad del uso de buprenorfina parche transdérmico en pacientes con dolor neuropático / Efficacy and safety of the use of buprenorphine transdermal patch in patients with neuropathic pain

INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso de buprenorfina 35mcg/hr parche transdérmico para el tratamiento del dolor neuropático. El dolor neuropático es consecuencia de un "daño" al sistema somato sensorial, que puede ocurrir por una variedad de etiologías entre las que se encuentran traumatismo vertebro medular, neuropatía diabética, neuralgia post-herpética, neuropatía post-quirúrgica, radiculopatía lumbar, dolor neuropático asociado a cáncer, neuropatía relacionada al virus de inmunodeficiencia humana, dolor fantasma, neuralgia del trigémino, entre otros. A nivel global, la prevalencia del dolor neuropático oscila entre 7% y 10% en población general. El dolor neuropático posee particularidades que implican un desafío para su manejo. Así, éste puede desencadenarse por algún estímulo sensorial o producirse espontáneamente; también puede presentar variaciones de acuerdo al tipo de paciente y la condición específica de fondo, debido a los diferentes mecanismos que operan en cada individuo. Todo ello, dificulta la elección del analgésico, por lo que existe más de un algoritmo de tratamiento para el dolor neuropático, que incluye el uso de medicamentos antiepilépticos, antidepresivos y opioides. En EsSalud, se dispone de medicamentos antiepilépticos y antidepresivos para el tratamiento del dolor neuropático como gabapentina y amitriptilina, entre otros. En caso de requerir el uso de opioides para el control del dolor neuropático se cuenta con tramadol y en el caso de dolor neuropático oncológico, se cuenta además con oxicodona y morfina. Sin embargo, los pacientes que suscitaron la solicitud de uso de buprenorfina transdérmica a ser evaluada en el presente dictamen, poseen condiciones clínicas particulares que dificultan el uso de las opciones de tratamiento incluidas actualmente en el Petitorio Farmacológico de la institución. Por lo que, existe la necesidad de contar con una alternativa eficaz y segura, dentro del grupo de medicamentos opioides, para el tratamiento del dolor neuropático en dicho grupo de pacientes. METODOLOGÍA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de buprenorfina en parche transdérmico para el dolor neuropático. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como la Food and Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente, se revisaron las bases de datos de PubMed, TRIPDATABASE y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como The National Institute for Health and Care Excellence (NICE). RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de buprenorfina transdérmica para el tratamiento de dolor neuropático. En la presente sinopsis se describe la evidencia disponible. CONCLUSIONES: El presente dictamen tuvo como objetivo evaluar la eficacia y seguridad del uso de buprenorfina transdérmica en parches para el tratamiento del dolor neuropático. Como parte de la evaluación se prestó especial atención a los pacientes con enfermedad renal crónica concomitante o que no tienen una vía de administración alternativa para el medicamento analgésico. De acuerdo a lo revisado, no hay evidencia disponible que sugiera que la buprenorfina transdérmica sea más eficaz, comparado con otras opciones de tratamiento incluidas en el Petitorio Farmacológico de EsSalud, para el tratamiento del dolor neuropático. Sin embargo, existe alguna evidencia del uso de buprenorfina transdérmica en pacientes que presentan eventos adversos, los cuales llevan a la suspensión o disminución de la dosis del opioide, o que presentan pobre acceso a la vía de administración del medicamento analgésico, condiciones que incluyen a la insuficiencia renal concomitante y dificultad para otras vías de administración (i.e. vía oral, vía de acceso para bloqueo neural). Así, dentro de la búsqueda realizada se identificó un estudio observacional que evaluó el uso de buprenorfina transdérmica para dolor neuropático, publicado por Filitz et al. Adicionalmente, también se identificó evidencia indirecta en torno al uso de buprenorfina transdérmica en pacientes que presentan dificultad para otras vías de administración. Esta evidencia proviene de dos guías de práctica clínica en pacientes con dolor oncológico, las guías de Scottish Intercollegiate Guidelines Network del 2013 y la guía de European Society for Medical Oncology 2012. Asimismo, debido a la escasez de evidencia científica sólida proveniente de ensayos clínicos aleatorizados y controlados; se incluyó también la opinión de expertos, cuya opinión se condice con la evidencia encontrada. En conclusión, la evidencia encontrada en torno a la eficacia y seguridad del uso de buprenorfina transdérmica como opción de analgésico para pacientes con dolor neuropático no ha probado que este sea más eficaz que otros tratamientos analgésicos actualmente aprobados en el Petitorio Farmacológico de la institución. Sin embargo, existe un grupo de pacientes, los cuales presentan insuficiencia renal concomitante o dificultan para otras vías de administración que requieren una alternativa de analgésico distinta. La evidencia de uso de buprenorfina transdérmica en estos pacientes proviene de estudios observacionales o evidencia indirecta, que de acorde con la opinión de expertos supondría una opción de tratamiento valida. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación- IETSI, aprueba el uso de buprenorfina transdérmica en pacientes con dolor neuropático que presentan insuficiencia renal concomitante o dificultad para otras vías de administración, y que por lo tanto no puedan utilizar las alterativas incluidas en el Petitorio Farmacológico de EsSalud; según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año, la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que poda surgir en el tiempo.

Análisis de costo-efectividad de los medicamentos utilizados para el tratamiento de pacientes con dolor neuropático en Colombia / Cost-effectiveness analysis of drugs used for the treatment of patients with neuropathic pain in Colombia

INTRODUCCIÓN: El análisis de costo-efectividad de ácido tióctico, acetaminofén y tramadol, acetaminofén e hidrocodona, tramadol, amitriptilina, imipramina, valproato, acetaminofén y codeína, buprenorfina, capsaicina, carbamazepina, parches de fentanyl, tapentadol, duloxetina, gabapentina, parches de lidocaína, oxcarbazepina, pregabalina para el tratamiento de pacientes con dolor neuropatico en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Con respecto a la condición de salud de interés, la asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por consecuencia directa de una lesión o enfermedad del sistema nervioso somatosensitivo. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. El dolor neuropático es causado por diversos trastornos que afectan el sistema nervioso central y perifér

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

A Cohort Comparison of Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome.

OBJECTIVES: To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol. STUDY DESIGN: This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome. RESULTS: A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups. CONCLUSION: The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.

American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.

The Centers for Disease Control have recently described opioid use and resultant deaths as an epidemic. At this point in time, treating this disease well with medication requires skill and time that are not generally available to primary care doctors in most practice models. Suboptimal treatment has likely contributed to expansion of the epidemic and concerns for unethical practices. At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it. This "Practice Guideline" was developed to assist in the evaluation and treatment of opioid use disorder, and in the hope that, using this tool, more physicians will be able to provide effective treatment. Although there are existing guidelines for the treatment of opioid use disorder, none have included all of the medications used at present for its treatment. Moreover, few of the existing guidelines address the needs of special populations such as pregnant women, individuals with co-occurring psychiatric disorders, individuals with pain, adolescents, or individuals involved in the criminal justice system. This Practice Guideline was developed using the RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) - a process that combines scientific evidence and clinical knowledge to determine the appropriateness of a set of clinical procedures. The RAM is a deliberate approach encompassing review of existing guidelines, literature reviews, appropriateness ratings, necessity reviews, and document development. For this project, American Society of Addiction Medicine selected an independent committee to oversee guideline development and to assist in writing. American Society of Addiction Medicine's Quality Improvement Council oversaw the selection process for the independent development committee. Recommendations included in the guideline encompass a broad range of topics, starting with the initial evaluation of the patient, the selection of medications, the use of all the approved medications for opioid use disorder, combining psychosocial treatment with medications, the treatment of special populations, and the use of naloxone for the treatment of opioid overdose. Topics needing further research were noted.