Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus

Introduction: Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society.

Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field.

Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.     

Integrating injectable opioid agonist treatment into a drug treatment court program: A case study

Background: A substantial proportion of individuals involved with the North American criminal justice system are convicted for drug-related activities. Drug treatment court (DTC) programs were developed as an alternative to incarceration for drug-related offences and aim to prioritize addiction treatment and improve health and social outcomes; however, only a fraction of DTC participants have access to first-line medications for opioid use disorder (OUD). Further, despite emerging evidence for the efficacy of injectable opioid agonist therapy (OAT) in treating individuals with severe OUD where past treatment attempts with first-line therapies have been unsuccessful, this treatment has never, to our knowledge, been implemented in correctional settings. Case: An individual in their 50s with a history of severe OUD, multiple interactions with the criminal justice system, and prior unsuccessful treatment attempts with methadone was initiated on injectable treatment with diacetylmorphine. The patient received 300?mg of diacetylmorphine witnessed 3 times daily at a supervised injection clinic. During a 1.5-year stabilization phase, the patient’s illicit opioid use significantly reduced. They subsequently enrolled in a DTC program for drug-related charges preceding initiation on injectable OAT and remained on this therapy during 16 months in DTC. Following graduation from DTC, the patient continued to receive treatment and returned to gainful employment in the community, with no further charges or episodes of incarceration. Discussion: This case describes the successful completion of a DTC program by an individual prescribed injectable OAT for severe OUD. The patient’s treatment plan played an integral role in DTC graduation and long-term adherence, leading to improved health and social outcomes, including cessation of illicit drug use, enhanced quality of life, and improved social functioning. The case highlights the potential benefits of a stepped and integrated approach to addiction treatment in DTC programs.     

Trajectories of retention in opioid agonist therapy in a Canadian setting

BackgroundLong-term engagement in opioid agonist therapy (OAT) has been consistently associated with reduced risk for morbidity and mortality in people with opioid use disorder (OUD). However, the dynamic nature of engagement/disengagement in OUD care for over time is poorly captured by traditional metrics. We characterized long-term longitudinal trajectories of engagement in OAT in Vancouver, Canada, between 2005 and 2018.MethodsData were derived from two community-recruited prospective cohorts of people who use drugs. Retention in OAT was defined as self-reported enrolment in OAT for two consecutive follow-up periods (an approximately six-month retention interval). We used latent class growth analysis to identify OAT engagement trajectories during the first five years after OAT initiation and multivariable logistic regression to evaluate predictors of trajectory group membership.ResultsWe identified four OAT retention trajectories among 438 OAT initiators: “consistently high” (36%), “consistently low” (23%), “increasing” (23%), and “decreasing” (15%). Employment was a significant cross-cutting predictor of membership of all sub-optimal OAT engagement patterns compared to consistently high trajectories. We also found that initiating OAT after 2014 (when regulatory changes to the provincial OAT program were introduced) was associated with the “consistently low” engagement group relative to others.ConclusionsWe identified four distinct OAT engagement trajectories in Vancouver, Canada, with employment being a common predictor of sub-optimal care trajectories, suggesting the need to explore alternative OAT models to address employment-related barriers. Care trajectory analysis could help inform tailored interventions to specific populations of people with OUD at specific time points to improve engagement in OAT, and decrease opioid-related morbidity and mortality.     

A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder

BackgroundBuprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine. MethodsWe examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS). ResultsAmong AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ ²₍₁₎ = 4.33, P = .04). ConclusionWe found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.     

In their own voices: Breaking the vicious cycle of addiction,treatment and criminal justice among people who inject drugs in Ukraine

Aims: To understand how perceived law enforcement policies and practices contribute to the low rates of utilisation of opioid agonist therapies (OAT) like methadone and buprenorphine among people who inject drugs (PWIDs) in Ukraine. Methods: Qualitative data from 25 focus groups (FGs) with 199 opioid-dependent PWIDs in Ukraine examined domains related to lived or learned experiences with OAT, police, arrest, incarceration and criminal activity and were analysed using grounded theory principles. Findings: Most participants were male (66%), in their late 30s, and previously incarcerated (85%), mainly for drug-related activities. When imprisoned, PWIDs perceived themselves as being “addiction-free”. After prison-release, the confluence of police surveillance and societal stress contributed to participants’ drug use relapse, perpetuating a cycle of searching for money and drugs, followed by re-arrest and re-incarceration. Fear of police and arrest both facilitated OAT entry and simultaneously contributed to avoiding OAT since system-level requirements identified OAT clients as targets for police harassment. OAT represents an evidence-based option to “break the cycle”; however, law enforcement practices still thwart OAT capacity to improve individual and public health. Conclusion: In the absence of structural changes in law enforcement policies and practices in Ukraine, PWIDs will continue to avoid OAT and perpetuate the addiction cycle with high imprisonment rates.     

Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report

Background: Opioid use disorders (OUD) translate into major health, social, and economic consequences. Opioid agonist medications, which generally require long-term administration, are the mainstay pharmacological treatment of OUD. However, a large proportion of individuals with OUD either refuse or fail to respond to these therapies. Ibogaine, a naturally occurring substance found in the Tabernanthe iboga plant, has shown potential to bring about transformative or spiritual experiences that have reportedly been associated with long-term abstinece. Although research on ibogaine is limited, an ibogaine subculture persists, offering unregulated ibogaine preparations for the treatment of addiction. Case presentation: We describe the case of a 37-year-old female with a 19-year history of severe OUD achieving an ongoing 18-month period of abstinence following a four-day ibogaine treatment. Her previous longest period of continuous abstinence from opioids was two months while on methadone. No safety issues associated with ibogaine were observed. Conclusions: A four-day treatment with ibogaine was succesful in achieving long-term remission of a previously treatment-refractory patient with severe OUD. While rigorous trials are required to establish safety and efficacy, future studies should seek to delineate the potential role of ibogaine or other molecules that may produce transformative experiences for individuals with substance use disorder.     

An ethical analysis of medication treatment for opioid use disorder (MOUD) for persons who are incarcerated

Abstract

Opioid use disorder (OUD) is highly prevalent among persons who are incarcerated. Medication treatment for opioid use disorder (MOUD), methadone, buprenorphine, and naltrexone, is widely used to treat OUD in the community. Despite MOUD’s well-documented effectiveness in improving health and social outcomes, its use in American jails and prisons is limited.

Several factors are used to justify limited access to MOUD in jails and prisons including: “uncertainty” of MOUD’s effectiveness during incarceration, security concerns, risk of overdose from MOUD, lack of resources and institutional infrastructure, and the inability of people with OUD to provide informed consent. Stigma regarding MOUD also likely plays a role. While these factors are relevant to the creation and implementation of addiction treatment policies in incarcerated settings, their ethicality remains underexplored.

Using ethical principles of beneficence/non-maleficence, justice, and autonomy, in addition to public health ethics, we evaluate the ethicality of the above list of factors. There is a two-fold ethical imperative to provide MOUD in jails and prisons. Firstly, persons who are incarcerated have the right to evidence-based medical care for OUD. Secondly, because jails and prisons are government institutions, they have an obligation to provide that evidence-based treatment. Additionally, jails and prisons must address the systematic barriers that prevent them from fulfilling that responsibility. According to widely accepted ethical principles, strong evidence supporting the health benefits of MOUD cannot be subordinated to stigma or inaccurate assessments of security, cost, and feasibility. We conclude that making MOUD inaccessible in jails and prisons is ethically impermissible.     

A systematic review of qualitative evidence on barriers to and facilitators of the implementation of opioid agonist treatment (OAT) programmes in prisons

BackgroundOpioid Agonist Treatment (OAT) programmes are regarded as a gold standard treatment for people living with Opioid Use Disorders (OUDs). However, OAT programmes are often unavailable or poorly implemented in prisons, in spite of the large numbers of people living with OUDs and the high risk of HIV transmission in prison settings. Unusually, this systematic review synthesizes qualitative evidence relating to barriers to, and facilitators of, the implementation of OAT programmes in prisons in high- and low/middle-income countries (LMICs) to provide more nuanced, contextualised understandings of how prison stakeholders perceive and/or experience OAT programmes within different prison settings.MethodsWe systematically reviewed six electronic databases for studies published between January 2005 and December 2019 involving prison stakeholders: policy-makers, governors, healthcare staff, prison officers, and prisoners. The search identified 8091 studies, of which only 16 incorporated qualitative methods (including qualitative elements of mixed methods) and met our quality criteria. Four of these studies were conducted in LMICs (Kyrgyzstan, Iran (2) and Indonesia).ResultsFindings were organized under three broad themes: (1) perceived benefits of OAT programmes; (2) barriers to the implementation and development of OAT programmes; and (3) treatment processes.DiscussionA lack of a clear understanding of the roles of OAT programmes and doubts regarding their effectiveness for people living with OUDs in prisons are critical barriers to prisoner participation in both high-and LMIC countries. Prison systems, particularly in LMICs, often lack the resources to mitigate problems with implementation. This review highlights an urgent need to develop further qualitative studies into prison OAT programmes, employing varied methods to explore such contexts in greater depth and minimize the impact of harms relating to OUDs in prisons.     

Factors associated with contingency management adoption among opioid treatment providers receiving a comprehensive implementation strategy

Background: Contingency management (CM) is an evidence-based behavioral intervention for opioid use disorders (OUDs); however, CM adoption in OUD treatment centers remains low due to barriers at patient, provider, and organizational levels. In a recent trial, OUD treatment providers who received the Science to Service Laboratory (SSL), a multilevel implementation strategy developed by a federally funded addiction training center, had significantly greater odds of CM adoption than providers who received training as usual. This study examined whether CM adoption frequency varied as a function of provider sociodemographic characteristics (i.e., age, race/ethnicity, licensure) and perceived barriers to adoption (i.e., patient-, provider-, organization-level) among providers receiving the SSL in an opioid treatment program. Methods: Thirty-nine providers (67% female, 77% non-Hispanic white, 72% with specialty licensure, M_age = 42 [SD = 11.46]) received the SSL, which consisted of didactic training, performance feedback, specialized training of internal change champions, and external coaching. Providers completed a comprehensive baseline assessment and reported on their adoption of CM biweekly for 52 weeks. Results: Providers reported using CM an average of nine 2-week intervals (SD = 6.35). Hierarchical multiple regression found that providers identifying as younger, non-Hispanic white, and without addiction-related licensure all had higher levels of CM adoption frequency. Higher perceived patient-level barriers predicted lower levels of CM adoption frequency, whereas provider- and organization-level barriers were not significant predictors. Conclusions: The significant effect of age on CM adoption frequency was consistent with prior research on predictors of evidence-based practice adoption, whereas the effect of licensure was counter to prior research. The finding that CM adoption frequency was lower among racially/ethnically diverse providers was not expected and suggests that the SSL may require adaptation to meet the needs of diverse opioid treatment providers. Entities using the SSL may also wish to incorporate a more explicit focus on patient-level barriers.     

Gender-specific predictors of methadone treatment outcomes among African Americans at an urban clinic

Background: African American patients with opioid use disorder (OUD) have demonstrated poorer methadone maintenance treatment (MMT) outcomes compared with white patients. This issue is further complicated in urban settings, where African Americans experience high rates of poverty and publicly funded treatment. Despite interrelated factors that disadvantage African Americans, the literature focusing on this population is scant. To address this shortcoming, we conducted the first investigation of gender differences and gender-specific MMT outcome predictors among African Americans (or any racial minority population). This study provides gender-specific findings to improve African American MMT outcomes. Methods: We studied 211 African American patients (male: n?=?137, 64.9%) at an urban, university-affiliated MMT clinic. We used existing intake data to assess baseline demographic, substance use, mental health, and interpersonal factors. Primary outcomes were 3-month drug⁺ (positive) urine drug screen (UDS) results and treatment retention. Results: Women were more likely (than men) to endorse histories of interpersonal violence, substance abuse in their social network, and mental health problems. Men reported a greater likelihood (than women) for early opioid-use onset and a lack of prior MMT. There were no gender differences in 3-month drug⁺ UDS or treatment retention. In multivariable analyses among women, no baseline factors predicted 3-month opioid⁺ UDS and physical abuse history predicted a higher proportion of 3-month cocaine⁺ UDS. Among men, primary injection opioid use and older age best predicted a higher proportion of 3-month cocaine⁺ UDS and parent substance abuse predicted shorter retention. In both gender-stratified analyses, higher proportions of 3-month opioid⁺ UDS and cocaine⁺ UDS predicted shorter retention. Conclusions: This study offers an analysis of gender differences in risk factors, MMT outcomes, and gender-specific predictors among African American patients. MMT clinics should tailor assessment and treatment protocols to address gender-specific needs.     

Consideration of opioid agonist treatment in a pregnant adolescent: A case report and literature review

Abstract

Background: Opioid use greatly increases the risk of overdose death, as well as contracting human immunodeficiency virus (HIV) and hepatitis. Opioid agonist treatment is recommended for pregnant women who are dependent on opioids. However, there is a dearth of studies on the use of opioid agonist treatment in pregnant teenagers. Case: Ms. A, a 15?year-old G1PO in foster care, presented to our tertiary women’s hospital requesting opioid agonist treatment for use of pill opioids. She reported nasal inhalation of 5–6 opioid tablets daily, with recent attempts to self-taper using nonprescribed buprenorphine since learning of her pregnancy. Last reported opioid use was >24?hours prior to admission. Urine drug testing was positive only for opioids (negative for buprenorphine and methadone). She did not exhibit significant withdrawal symptoms while hospitalized. The psychiatric treatment team recommended deferring opioid agonist treatment and pursuing outpatient substance use treatment. Unfortunately, Ms. A did not attend outpatient treatment and was lost to follow up. Discussion: Based upon our experience and review of the studies regarding opioid use disorder (OUD) and perinatal and adolescent opioid use, we recommend that pregnant adolescents with OUD be referred to opioid agonist treatment with buprenorphine or methadone. Studies specifically addressing opioid agonist treatment in pregnant teenagers are needed.     

“How will I get my next week's script?” Reactions of Reddit opioid forum users to changes in treatment access in the early months of the coronavirus pandemic

BackgroundThe COVID-19 pandemic poses significant challenges to people with opioid use disorder (OUD). As localities enforce lockdowns and pass emergency OUD treatment regulations, questions arise about how these changes will affect access and retention in care. In this study, we explore the influence of COVID-19 on access to, experiences with, and motivations for OUD treatment through a qualitative analysis of public discussion forums on Reddit.MethodsWe collected data from Reddit, a free and international online platform dedicated to public discussions and user-generated content. We extracted 1000 of the most recent posts uploaded between March 5th and May 13th, 2020 from each of the two most popular opioid subreddits “r/Opiates” and “r/OpiatesRecovery” (total 2000). We reviewed posts for relevance to COVID-19 and opioid use and coded content using a hybrid inductive-deductive approach. Thematic analysis identified common themes related to study questions of interest.ResultsOf 2000 posts reviewed, 300 (15%) discussed topics related to the intersection of opioid use and COVID-19. Five major themes related to OUD treatment were identified: Concern about closure of OUD treatment services; transition to telehealth and virtual care; methadone treatment requirements and increased exposure to COVID-19; reactions to changing regulations on medications for OUD; and influences of the pandemic on treatment motivation and progress.ConclusionIn the face of unprecedented challenges due to COVID-19, reactions of Reddit opioid forum users ranged from increased distress in accessing and sustaining treatment, to encouragement surrounding new modes of treatment and opportunities to engage in care. New and less restrictive avenues for treatment were welcomed by many, but questions remain about how new norms and policy changes will be sustained beyond this pandemic and impact OUD treatment access and outcomes long-term.     

Adults who misuse opioids: Substance abuse treatment use and perceived treatment need

Background: Opioid use disorder (OUD) and overdose deaths among the US population continue to increase. This study examined associations of OUD and other substance use disorders with substance abuse treatment use and perceived treatment need among US adults aged 18+ who misused opioids. Methods: The 2015–2016 National Survey on Drug Use and Health provided data (n?=?5100 respondents who misused opioids in the past year). We used multivariable logistic regression models to examine associations of opioid and other substance use disorders with treatment use and perceived treatment need, adjusting for sociodemographic and health statuses. Results: The data showed that 4.7% of adults misused opioids and 19.1% of those who misused had an OUD. Of those with an OUD, only 31.5% had received substance abuse treatment in the past year and 13.6% perceived the need for such treatment. Of those with an OUD, heroin use disorder (adjusted odds ratio [AOR]?=?2.59, 95% confidence interval [CI]?=?1.59–4.23) and having been arrested/booked (AOR?=?1.98, 95% CI?=?1.18–3.33) were associated with higher odds of receiving treatment, whereas lack of health insurance (AOR?=?0.49, 95% CI?=?0.25–0.94) was associated with lower odds. Heroin use disorder (AOR?=?2.16, 95% CI?=?1.23–3.83) and higher mental health impairment scores (AOR?=?1.05, 95% CI?=?1.01–1.09) were associated with higher odds of perceived treatment need. Conclusions: The overall low socioeconomic status and high rates of polysubstance use disorders among those with OUD indicate that they need financial and other help to access treatment and relapse prevention services. The very low rates of perceived treatment need also point to the need for strategies to increase individuals’ recognition of their need for treatment.     

Pharmacotherapeutic management of co-morbid alcohol and opioid use

ABSTRACT

Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite prevalent, yet there are no pharmacological treatment approaches specifically designed to treat co-morbid OUD and AUD. Here, the authors critically summarize OUD, AUD and opioid/alcohol co-use and their current pharmacotherapies for treatment. They also review the mechanisms of action of opioids and alcohol within the brain reward circuitry and discuss potential combined mechanisms of action and resulting neuroadaptations. Pharmacotherapies that aim to treat AUD or OUD that may be beneficial in the treatment of co-use are also highlighted. Preclinical models assessing alcohol and opioid co-use remain sparse. Lasting neuroadaptations in brain reward circuits caused by co-use of alcohol and opioids remains largely understudied. In order to fully understand the neurobiological underpinnings of alcohol and opioid co-use and develop efficacious pharmacotherapies, the preclinical field must expand its current experimental paradigms of ‘single drug’ use to encompass polysubstance use. Such studies will provide insights on the neural alterations induced by opioid and alcohol co-use, and may help develop novel pharmacotherapies for individuals with co-occurring alcohol and opioid use disorders.     

Utilization of buprenorphine and methadone among opioid users who inject drugs

ABSTRACT

Background: There has been a rise in opioid abuse and related injection drug use in the United States, and treatment for opioid use disorders may be underutilized. The study aim was to describe utilization of opioid agonist therapy (OAT), and assess factors associated with utilization of OAT, among persons who inject drugs (PWID) in the Seattle metropolitan area. Methods: Data were obtained from the 2015 National HIV Behavioral Surveillance (NHBS) system among PWID in the Seattle area. Persons aged ≥18 years who injected drugs in the past year were recruited using respondent-driven sampling. Local supplemental questions assessed whether participants had received methadone or buprenorphine treatment in the past year. The analysis was restricted to participants who reported use of any opioids in the past year. Analyses compared the demographic, health insurance status, duration of injection drug use, prior history of overdose, prior receipt of hepatitis C virus/human immunodeficiency virus (HCV/HIV) testing (self-report), and screening positive for HCV/HIV via study testing between methadone- or buprenorphine-treated and untreated PWID. Multivariate logistic models were performed to assess adjusted associations with receipt of any OAT. Results: The sample included 487 PWID who used opioids in the past year, of whom 27.1% (95% confidence interval [CI]: 23.1–31.1) reported past-year treatment with methadone and 4.7% (95% CI: 2.8–6.6) reported treatment with buprenorphine. There were no significant differences in demographics among participants who did and did not report past-year OAT; however, participants who were treated with methadone were more likely to be insured and have hepatitis C. After adjustment for other covariates, having health insurance was strongly associated with receipt of OAT (adjusted odds ratio [aOR] = 18.6; 95% CI: 2.5–138.7). Conclusions: OAT, in particular buprenorphine, has been underutilized by opioid-using PWID in the Seattle area. Health insurance is a critical factor for enabling PWID to utilize OAT treatment for opioid use disorders.     

Training in office-based opioid treatment with buprenorphine in US residency programs: A national survey of residency program directors

Background: The prevalence of opioid use disorder (OUD) has increased sharply. Office-based opioid treatment with buprenorphine (OBOT) is effective but often underutilized because of physicians' lack of experience prescribing this therapy. Little is known about US residency training programs' provision of OBOT and addiction medicine training. Methods: The authors conducted a survey of residency program directors (RPDs) at all US residency programs in internal medicine, family medicine, and psychiatry to assess the frequency with which their residents provide care for OUD, presence and features of curricula in OBOT and addiction medicine, RPDs' beliefs about OBOT, and potential barriers to providing OBOT training. Results: The response rate was 49.5% (476 of 962). Although 76.9% of RPDs reported that residents frequently manage patients with OUD, only 23.5% reported that their program dedicates 12 or more hours of curricular time to addiction medicine, 35.9% reported that their program encourages/requires training in OBOT, and 22.6% reported that their program encourages/requires obtaining a Drug Enforcement Administration (DEA) waiver to prescribe buprenorphine. Most RPDs believe that OBOT is an important treatment option for OUD (88.1%) and that increased residency training in OBOT would improve access to OBOT (73.7%). The authors also found that programs whose RPD had favorable views of OBOT were more likely to provide OBOT and addiction medicine training. Psychiatry programs were most likely to provide OBOT training and their RPDs most likely to have beliefs about OBOT that were positive. Commonly cited barriers to implementing OBOT training include a lack of waivered preceptors (76.9%), competing curricular priorities (64.1%), and a lack of support (social work and counseling) services (54.0%). Conclusions: Internal medicine, family medicine, and psychiatry residents often care for patients with OUD, and most RPDs believe that increased residency training in OBOT would increase access to this treatment. Yet, only a minority of programs offer training in OBOT.