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.     

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.     

Lacking evidence for the association between frequent urine drug screening and health outcomes of persons on opioid agonist therapy

BackgroundOpioid agonist therapy (OAT) is a first-line treatment for opioid use disorder (OUD); however, the efficacy and role of urine drug screening (UDS) in OAT has received little research attention. Prior evidence suggests that UDS frequency reflects philosophy and practice context rather than differences in patient characteristics or clinical need. Therefore, we reviewed the literature on the effect of and recommendations for the frequency of UDS on health outcomes for persons with OUD who receive OAT.MethodsWe searched Medline and EMBASE for articles published from 1995-2017. Search results underwent double, independent review with discrepancies resolved through discussion with a third reviewer, when necessary. Additional articles were identified through snowball searching, hand searching (Google Scholar), and expert consultation. The Cochrane tool was used to assess risk of bias.ResultsOf the 60 potentially eligible articles reviewed, only one three-arm randomized open-label trial, comparing weekly and monthly UDS testing with take-home OAT doses, met our inclusion criteria.ConclusionsOur review identified an urgent gap in research evidence underpinning an area of clinical importance and that is routinely reported by patients as an area of concern.     

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.     

Double-blind injectable hydromorphone versus diacetylmorphine for the treatment of opioid dependence: A pilot study

Using data from the North American Opioid Maintenance Initiative study, a Phase III randomized and parallel arm trial, this pilot study is aimed at testing if treatment response with injectable hydromorphone differs compared to diacetylmorphine in the treatment of long-term opioid addiction. A total of 140 long-term, treatment-refractory opioid-dependent individuals received either injectable diacetylmorphine (n = 115) or hydromorphone (n = 25), in a double-blind fashion, over 12 months. At the end of the study, none of the participants in the hydromorphone group thought they were definitely receiving this drug. Retention rates at 12 months with diacetylmorphine (87.8%; 95% confidence interval [CI] = 80.5%–92.7%) and hydromorphone (88.0%; 95% CI = 68.7%–96.1%) were virtually identical. The use of illicit heroin in the prior month declined from a mean of 26.6 and 26.3 days at baseline to 5.3 and 5.2 days at 12 month in the diacetylmorphine and hydromorphone groups, respectively. There were no differences between diacetylmorphine and hydromorphone in the adjusted mean scores of the European Addiction Severity Index. There were no differences in the safety profile of the medications. Hydromorphone may be similarly safe and effective as diacetylmorphine as opioid-agonist substitution treatment; future studies are required to confirm it. Further study will also be required to show that open-label hydromorphone can also successfully attract patients into care and retain them.     

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.     

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.     

Underutilization of the current clinical capacity to provide buprenorphine treatment for opioid use disorders within the Veterans Health Administration

Background: Opioid use disorder (OUD) is a critical concern among US veterans. The Veterans Health Administration (VHA) recommends buprenorphine as a first-line treatment for OUD; however, only 35% of veterans with an OUD currently receive medication treatment. Practical barriers, including the capacity of providers to prescribe, may affect delivery of buprenorphine. We examined the current state of buprenorphine treatment within the VHA. Methods: National VHA administrative databases were queried to identify all providers credentialed to prescribe buprenorphine as of January 2018. Data were extracted on providers’ prescribing capacity (30, 100, or 275 patients concurrently) and number of patients who received buprenorphine in the prior 180?days. Results: A total of 1458 VHA providers were credentialed to prescribe buprenorphine. Forty-three percent of providers had not prescribed buprenorphine to any VHA patients in the past 180?days. Of those that prescribed to at least 1 patient, providers still prescribed to fewer patients than their capacity, regardless of their patient panel size (30, 100, or 275), prescribing to 18.5 patients on average. Conclusions: VHA providers are prescribing buprenorphine below their capacity. A multipronged approach to increase the number of credentialed providers and address barriers to prescribing is needed to ensure that veterans get effective treatment for OUD.     

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.     

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.     

Chronic High-Dose Buprenorphine Does Not Block Subjective High from Diacetylmorphine in a Patient in Heroin-Assisted Treatment

ABSTRACT

We present the case of a 35-year-old woman in heroin-assisted treatment (HAT) expressing the wish for the transition to oral opioid agonist treatment. After failed attempts to change to oral diacetylmorphine and slow-release oral morphine, respectively, she was induced on overlapping buprenorphine (BUP) treatment with the Bernese method. Gradual dose increases to BUP 48 mg per day did not result in attenuation of subjective effects of IV diacetylmorphine (DAM) 190 mg. Instead, the patient showed increased sedation. BUP was then reduced to 32 mg per day. After the gradual reduction of IV DAM, she reinitiated illicit substance use. IV DAM was again raised to an effective dose leading to stabilization and reduction of illicit substance use. BUP was subsequently reduced to 8 mg per day. This combination was continued as the patient felt comfortable and reported less early morning withdrawal than with exclusive DAM treatment. We discuss possible underlying mechanisms and explanations as well as clinical implications.     

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.     

Initiation of injectable opioid agonist treatment in hospital: A case report

Uncontrolled opioid withdrawal and pain often drive inpatients with opioid use disorder to leave hospital against medical advice, resulting in suboptimal medical and addiction treatment. When oral opioid agonist treatments such as methadone and buprenorphine/naloxone fail for management of craving and withdrawal, injectable opioid agonist treatment may serve to retain patients in care and link them to addiction services. We describe the case of a 47‐year‐old man with a severe, active opioid use disorder and daily use of illicitly manufactured fentanyl, who was re‐admitted to hospital for post‐operative management after leaving against medical advice due to uncontrolled opioid withdrawal. Intravenous hydromorphone was used to retain him in care, allowing for completion of his antibiotics and enrolment in ongoing community injectable opioid agonist treatment.     

Predictors of treatment allocation guesses in a randomized controlled trial testing double-blind injectable hydromorphone and diacetylmorphine for severe opioid use disorder

Background: SALOME (Study to Assess Longer-term Opioid Medication Effectiveness) tested in a double-blind non-inferiority clinical trial if hydromorphone could be as effective as diacetylmorphine for severe opioid use disorder. Although participants did not guess treatment correctly beyond what is expected by chance, perceived treatment assignment could affect patients’ response to treatment. This study tested if treatment allocation guess is associated with treatment outcomes and identified predictors of guess.

Methods: Data were obtained through questionnaires and clinical records. Participants were asked what medication they thought they were receiving (diacetylmorphine, hydromorphone or unsure) and their open-ended reasons. Multinomial logistic regression was used to assess the predictors of treatment guess. An inductive thematic analysis was used to code open-ended responses. This clinical trial was registered with U.S. National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT01447212).

Findings: Participants referred to prior experiences with opioids and the presence or absence of specific drug effects as reasons for their guesses. There were no differences in illicit opioid use and retention by guess; however those who guessed diacetylmorphine had better physical and mental health scores. Participants with a treatment-related observed drowsiness event, and higher perceived drug-related high scores were more likely to guess diacetylmorphine compared to hydromorphone. Guessing hydromorphone was more likely among those who made negative comments as reasons for treatment guesses.

Conclusions: Understanding the clues participants use for treatment allocation guesses and relating them to treatment expectations could be integrated with accurate information about the treatment, providing an opportunity for patient–physician shared decision-making in opioid maintenance treatment.

Clinical trial registration: U.S. National Institutes of Health; ClinicalTrials.gov Identifier: NCT01447212; https://clinicaltrials.gov/ct2/show/NCT01447212