Low-Dose Buprenorphine Initiation for Opioid Agonist Therapy in Patients with Opioid Use Disorder: A Dutch Consensus Paper

Buprenorphine/naloxone has been shown to be an effective treatment of opioid use disorder. According to the Canadian National clinical practice guideline on the management of opioid use disorders, given the superior safety profile of buprenorphine/naloxone and its potential for flexible take-home dosing in comparison to other opioid agonist medication it is strongly recommended to initiate opioid agonist treatment with buprenorphine/naloxone as the preferred first-line treatment when possible. Due to its pharmacological properties induction can be challenging, requiring the cessation of all opioids for a certain amount of time to avoid the risk of precipitated withdrawal symptoms. For this reason, buprenorphine/naloxone is not initiated for the treatment of opioid use disorder in critically ill patients where continuous infusion of opioids are required for maintenance of sedation resulting in a missed opportunity for first line treatment of that patient's opioid use disorder. We present a case of a 29-year-old female with opioid use disorder admitted for infective endocarditis and septic shock requiring intubation for hypoxic respiratory failure secondary to bilateral lung septic emboli with a high opioid debt requiring higher than typical doses of fentanyl and dexmedetomidine infusions to maintain sedation with clinical objective sign of inadequate treatment of her pain and opioid withdrawal. She was successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require cessation of her fentanyl infusion. This case illustrates a new method for starting buprenorphine/naloxone in a critically ill intubated patient, where buprenorphine/naloxone was never a consideration in this specific patient population. This method can be used to minimize barriers to opioid agonist therapy in intubated patients.

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessSAMHSA Releases Guidance for Initiating Medication Treatment for Opioid OverdoseVabren WattsVabren WattsSearch for more papers by this authorPublished Online:3 Mar 2015https://doi.org/10.1176/appi.pn.2015.2a10AbstractOverdose deaths due to opioid prescription painkillers have quadrupled in the United States since 1999, but a new publication hopes to reduce that tragic number.As rates for opiate use disorder—including use of prescription painkillers and heroin—continue to rise in the United States, researchers, federal health agencies, and pharmaceutical manufacturers are focusing on pharmacotherapies that could help some individuals access treatment for the disorder in medical office settings rather than in specialized opioid treatment centers. Arisha Singh/shutterstockTo this end, the Substance Abuse and Mental Health Services Administration has published the guidance “Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide.” It provides a summary of the key differences between extended-release injectable naltrexone (naltrexone-ERI), methadone, and buprenorphine. “Medication-assisted treatment for opioid dependence is clearly well researched and has great safety and efficacy,” Petros Levounis, M.D., chair of the Department of Psychiatry at Rutgers New Jersey Medical School, said in an interview with Psychiatric News. “Yet, few psychiatrists and other physicians seem to be using these pharmacotherapies to treat opioid use disorder. The guidance is very necessary to spread the word about treatment options for opiate addiction.” According to the 2013 National Survey on Drug Use and Health, approximately 4.5 million people in the United States reported nonmedical use of prescription pain relievers in the prior month, and 289,000 reported use of heroin in the prior month. Despite the dimensions of the problem, the guidance noted, nearly 80 percent of people with an opioid use disorder do not receive treatment because of limited treatment capacity, financial obstacles, stigma associated with being enrolled in a treatment program, and other barriers to care.The guidance offers a step-by-step process for treating people with opioid use disorder, from assessing patients’ need for treatment to deciding when it is safe for patients to discontinue treatment. The guidance highlights the importance of documenting the patient’s substance use history, including alcohol and other drugs of abuse, as well as the history of comorbid general medical and psychiatric conditions to best prioritize and coordinate treatment management. It also stressed the importance of evaluating the patient’s degree of motivation for behavior change and readiness to participate in treatment. As it relates to medication options, the guidance highlights key distinctions among the medications approved by the Food and Drug Administration for treating opioid use disorder, such as the pharmacological category in which each one is classified. For example, “Unlike methadone and buprenorphine, extended-release injectable naltrexone [an opioid antagonist] has no potential for abuse and diversion and requires once-a-month dosing, which should be desirable to providers and some patients,” Joseph Liberto, M.D., associate chief of staff for education and academic affairs at the Veterans Administration of Maryland Health Care Center and a member of the expert panel that developed the new guidance, told Psychiatric News. In addition, Liberto, who is also an associate professor of psychiatry at the University of Maryland School of Medicine, stated that naltrexone-ERI can be prescribed by anyone licensed to prescribe medications, including physicians, nurse practitioners, and physician assistants without specialized board certification or specialized training—which is currently required for administering methadone, an opioid agonist. “Its availability therefore holds the promise of increasing access for people with opioid use disorder who have, up to now, gone untreated.”Maryland Treatment Centers Medical Director Marc Fishman, M.D., who also served on the guidance-development panel and is an assistant professor of psychiatry at Johns Hopkins Hospital, told Psychiatric News that though buprenorphine, a partial opioid agonist, is still considered “the first-line treatment” for opioid use disorder by most physicians, it’s a relief to have more options available to treat patients with opioid addiction. “Pharmacotherapies vary from person to person,” Fishman noted. “Whether the prevention medication be naltrexone, buprenorphine, or methadone, medication-assisted treatment should be the standard of care as an opportunity for treatment modality for every patient with opioid addiction.”As for Levounis, he said that health care professionals must continue to spread the word that evidence-based interventions for opioid use disorder are available and should be used to treat some patients with the disorder. “The tables and information in the guidance that compared the different treatment options were very helpful. I think that psychiatrists and primary care physicians, as well as patients, will benefit from what is presented in the document.” ■“Clinical Use of Extended–Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide” can be accessed here. ISSUES NewArchived

Toxicity of agents used for opioid withdrawal: a case-based approach.

Pediatric emergency departments (EDs) in the United States are facing a rise in the number of children and adolescents who present with opioid use disorder (OUD), often driven by illicitly manufactured fentanyl. Medication treatment of pediatric OUD in the ED setting is often limited to symptomatic treatment of opioid withdrawal. Pediatric patients are rarely offered medications for OUD, especially in the ED setting. Buprenorphine is a partial opioid agonist that is Food and Drug Administration-approved for the treatment of OUD in patients aged 16 years and older. Adult studies have demonstrated that ED initiation of medication for OUD such as buprenorphine is feasible, safely treats withdrawal symptoms, and can improve patient compliance with outpatient follow-up. However, initiation of buprenorphine in the ED has not been well-studied in the pediatric population. We present 2 cases of adolescent patients, a 16-year-old male and 17-year-old female, who presented to the ED with opioid withdrawal. They were both diagnosed with severe OUD because of their use of counterfeit pills containing fentanyl. Both patients were successfully started on buprenorphine/naloxone in the pediatric ED before transitioning to an outpatient addiction clinic for continued treatment. The case series demonstrates the feasibility of ED-based buprenorphine initiation for adolescents, an important and timely intervention for adolescents with OUD.

Guideline No. 443b: Opioid Use Throughout Women’s Lifespan: Opioid Use in Pregnancy and Breastfeeding

There are more than 200 opioid overdose deaths each day in the US. In combating this epidemic we look to available treatment tools. Here, we find only three medications approved by the Food and Drug Administration (FDA) for the treatment of opioid use disorder. Of the three, buprenorphine is of particular importance due to its reduced overdose potential as a partial opioid agonist. Evidence supports its clinical equivalence to its full agonist cousin methadone, and suggests that it is better slated for long-term treatment of opioid use disorder compared to the non-selective opioid antagonist naltrexone. Buprenorphine is most popularized within Suboxone, a medication which also contains the non-selective opioid antagonist naloxone. The naloxone has no additional effect when the drug is taken as instructed, as it is intended to prevent diversion in those that would attempt to inject the medication. While Suboxone is regarded by some as the future of medical treatment, others have expressed concerns. This review aims to explore the history, controversy, and open questions that surround buprenorphine and its most prescribed variation, Suboxone. These include its pharmacological, legislative, and social history, alternative indications, efficacy as a treatment of opioid use disorder, and more. Armed with this information, the reader will have a more in-depth and holistic understanding of the medication's place in their community.

Using Science to Battle Stigma in Addressing the Opioid Epidemic: Opioid Agonist Therapy Saves Lives

BackgroundDirect acting antiretrovirals (DAA) are effective for individuals who are infected with chronic hepatitis C virus (HCV), yet many people go without access to these lifesaving treatments.Materials and methodsWe conducted a non-randomized study evaluating treatment data for patients in outpatient treatment for opioid use disorder (OUD) at a private clinic. Patients who were HCV-positive, had been in OUD treatment for at least 4 weeks, and engaged in integrated HCV treatment with DAA (co-located within their treatment for OUD) were compared to patients with HCV who only received OUD treatment. We evaluated HCV cure; OUD medication adherence, treatment utilization and retention; and illicit substance use for those engaged in treatment between 9/2016 and 1/2018.ResultsSeventy-four patients completed integrated HCV-OUD treatment with DAA, with 87.8% achieving cure. Of the 66 who completed treatment and were subsequently evaluated for sustained viral response 98.5% were cured. Patients who received integrated HCV and OUD treatment in our clinic, stayed in OUD treatment longer, demonstrated higher OUD medication adherence, and used less opioids or cocaine compared to HCV-infected patients (n = 572) being treated only for OUD.DiscussionWe have reported on a reproducible intervention that lends itself to outpatient OUD treatment. Analyses demonstrate the potential positive impact HCV treatment has on OUD recovery, including reduction in opioid and cocaine use and increased retention in careConclusionCo-locating HCV treatment with existing OUD treatment is feasible, effective, and demonstrates positive outcomes for the treatment of both conditions.

Postpartum medication for opioid use disorder outcomes associated with prenatal treatment and neighborhood-level social determinants

Opioid and cocaine abuse are major public health burdens. Existing medications for opioid use disorder are limited by abuse liability and side effects, whereas no treatments are currently approved in the United States for cocaine use disorder. Dopamine D3 receptor (D3R) antagonists have shown promise in attenuating opioid and cocaine reward and mitigating relapse in preclinical models. However, translation of D3R antagonists to the clinic has been hampered by reports that the D3R antagonists GSK598,809 (5-(5-((3-((1S,5R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-3-azabicyclo[3.1.0]hexan-3-yl)propyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)-4-methyloxazole) and SB-277,011A (2-(2-((1r,4r)-4-(2-oxo-2-(quinolin-4-yl)ethyl)cyclohexyl)ethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile) have adverse cardiovascular effects in the presence of cocaine. Recently, we developed two structurally novel D3R antagonists, R-VK4-40 and R-VK4-116, which are highly selective for D3R and display translational potential for treatment of opioid use disorder. Here, we tested whether R-VK4-40 ((R)-N-(4-(4-(2-Chloro-3-ethylphenyl)piperazin-1-yl)-3-hydroxybutyl)-1H-indole-2-carboxamide) and R-VK4-116 ((R)-N-(4-(4-(3-Chloro-5-ethyl-2-methoxyphenyl)piperazin-1-yl)-3-hydroxybutyl)-1H-indole-2-carboxamide) have unwanted cardiovascular effects in the presence of oxycodone, a prescription opioid, or cocaine in freely moving rats fitted with surgically implanted telemetry transmitters. We also examined cardiovascular effects of the D3R antagonist, SB-277,011A, and L-741,626 (1-((1H-indol-3-yl)methyl)-4-(4-chlorophenyl)piperidin-4-ol), a dopamine D2 receptor-selective antagonist, for comparison. Consistent with prior reports, SB-277,011A increased blood pressure, heart rate, and locomotor activity alone and in the presence of cocaine. L-741,626 increased blood pressure and heart rate. In contrast, R-VK4-40 alone dose-dependently reduced blood pressure and heart rate and attenuated oxycodone-induced increases in blood pressure and oxycodone or cocaine-induced increases in heart rate. Similarly, R-VK4-116 alone dose-dependently reduced cocaine-induced increases in blood pressure and heart rate. These results highlight the safety of new D3R antagonists and support the continued development of R-VK4-40 and R-VK4-116 for the treatment of opioid and cocaine use disorders. SIGNIFICANCE STATEMENT: Opioid and cocaine abuse are major public health challenges and new treatments that do not adversely impact the cardiovascular system are needed. Here, we show that two structurally novel dopamine D3 receptor antagonists, R-VK4-40 and R-VK4-116, do not potentiate, and may even protect against, oxycodone- or cocaine-induced changes in blood pressure and heart rate, supporting their further development for the treatment of opioid and/or cocaine use disorders.

Back to table of contents Previous article Next article Clinical & ResearchFull AccessDocument Provides Inpatient Guidelines for Medication Treatment of Opioid Use DisorderAbhisek Chandan Khandai, M.D., Josie Francois, M.D.Abhisek Chandan KhandaiSearch for more papers by this author, M.D., Josie FrancoisSearch for more papers by this author, M.D.Published Online:21 Dec 2022https://doi.org/10.1176/appi.pn.2023.01.1.39AbstractA new resource document will help strengthen psychiatrists’ capabilities to be team leaders in the treatment of hospitalized patients with opioid use disorder. This article is one of a series coordinated by APA’s Council on Consultation-Liaison Psychiatry and the Academy of Consultation-Liaison Psychiatry.The prevalence, morbidity, mortality, and costs of opioid use disorder have dramatically increased over the past 20 years. While there are several effective and evidence-based medications for opioid use disorder (MOUD), less than 20% of Americans with opioid use disorder receive MOUD. The inpatient general hospital setting represents a critical point of access to MOUD, given the significant medical comorbidities of patients with opioid use disorder and the increased time to engage patients in treatment, better monitoring capabilities, and opportunities to reduce the monetary impact of the disorder on the health care system.Psychiatrists are an integral part of the hospital treatment team. However, they are often excluded for many reasons, including stigma toward opioid use disorder, lack of consultation-liaison (C-L) psychiatry services, and discomfort with managing opioid use disorder.To help address this care gap, APA’s Council on C-L Psychiatry, in collaboration with the Council on Addiction Psychiatry, convened a multispecialty expert workgroup to prepare a resource document related to the medication treatment of patients with opioid use disorder. The workgroup discussed several barriers to medication treatment and factors limiting the involvement of psychiatrists in the treatment of opioid and other substance use disorders in the inpatient hospital setting. Among the barriers they identified were stigma associated with substance use disorders (SUD) and a knowledge gap among psychiatrists regarding SUD treatment. The workgroup then created a resource document that seeks to address these barriers and guide general psychiatrists.The document includes an overview of OUD and its management in adults, explores the pharmacology of MOUD, describes barriers to care and specialty-specific concerns, and provides approaches to reducing stigma. The resource document also compares current medications to treat patients with opioid use disorder (naltrexone, buprenorphine, and methadone), walks psychiatrists through the medications’ initiation and titration in the general hospital setting, and provides recommendations on how to transition patients taking these medications from inpatient to outpatient settings.The resource guide is designed to educate and empower psychiatrists to take a larger role in MOUD in the general hospital setting to save more lives at reduced cost. Psychiatrists are in a strong position to oversee the use of MOUD in hospital settings and are best equipped to lead MOUD treatment and reduce stigma, given our relative expertise in the area of SUDs, comorbid psychiatric illnesses, and harm reduction strategies. As such, it is important that psychiatrists stay up to date on evidence-based MOUD and work with other specialties to promote psychiatric involvement in the care of those with opioid use disorder in the general hospital setting. ■Resource Document on the Treatment of Opioid Use Disorder in the General HospitalAbhisek Chandan Khandai, M.D., is a consultation-liaison psychiatry attending at UT Southwestern Medical Center and a member of APA’s Committee on Consultation-Liaison Psychiatry.Josie Francois, M.D., is a first-year psychiatry resident at Brigham and Women’s Hospital. ISSUES NewArchived

State medical cannabis laws, currently in place in 39 states and Washington, DC, provide an avenue for therapeutic use of cannabis to manage chronic noncancer pain stemming from conditions such as arthritis and low back pain. These laws may also influence cannabis and opioid addiction and overdose, for example, if people substitute cannabis in place of opioids to manage pain. No studies, to our knowledge, have examined how state medical cannabis laws influence health care use related to addiction to or overdose from cannabis or opioids among people with chronic noncancer pain. We used a difference-in-differences design and augmented synthetic control analyses comparing changes in cannabis use disorder (CUD) and opioid use disorder (OUD) treatment and cannabis and opioid overdose-related health care use before and after medical cannabis law implementation among Medicare beneficiaries with chronic noncancer pain in seven states (Florida, Maryland, Minnesota, New Hampshire, New York, Oklahoma, and Pennsylvania) relative to changes in outcomes over the same period in 17 comparison states (Alabama, Georgia, Idaho, Indiana, Iowa, Kansas, Kentucky, Mississippi, Nebraska, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Virginia, Wisconsin, and Wyoming) without medical cannabis laws. State medical cannabis laws had an estimated average effect of less than 0.005 percentage points on the overall proportion of patients receiving any CUD or OUD treatment, less than 0.009 percentage points on the proportion of patients newly initiating CUD or OUD treatment, and less than 0.0005 percentage points on the proportion of patients receiving overdose-related health care for cannabis or opioid overdoses (p > 0.05 for all findings). Our study did not identify effects of state medical cannabis laws on health care use related to CUD or OUD treatment or overdose among Medicare beneficiaries younger than age 65 years with chronic noncancer pain.

Female, Hispanic, and Black patients with opioid use disorder (OUD) are less likely to receive OUD medication treatment than other patients. The PROUD (PRimary care Opioid Use Disorders treatment) trial demonstrated that implementation of primary care (PC) nurse care management increases OUD medication treatment compared with usual care (UC). This study assessed whether the PROUD intervention's effect differed across sex, race and ethnicity. Secondary analyses of cluster-randomized implementation trial. 12 PC clinics (2 per health system) in five states in the USA, randomized to UC or intervention, stratified by health system. PC patients 16-90 years old. Three strategies to implement office-based addiction treatment (OBAT) by nurse care managers: (1) full-time nurse salary; (2) nurse training and technical assistance from expert nurses at Boston Medical Center; (3) ≥3 PC providers willing to prescribe buprenorphine. Nurses were trained in the Massachusetts model of OBAT which includes lowering barriers to OUD treatment, assessing and educating patients, supporting initiation of medications for OUD and providing ongoing medical management, in collaboration with PC providers. The primary outcome was a clinic-level measure of OUD treatment defined as patient-years of OUD treatment per 10 000 PC patients based on orders and procedures for buprenorphine or extended-release naltrexone from electronic health records and insurance claims (hereafter 'OUD treatment'). The mean numbers of patients seen by intervention and UC clinics at baseline were 18 485 and 22 557, respectively. Female patients comprised 60% of the total PC population in intervention clinics and 64% in UC clinics; Asian, Black, Hispanic or smaller racial groups comprised 61% of the PC population in intervention clinics, and 70% in UC clinics. Compared with UC, the intervention increased OUD treatment for male patients [adjusted difference: 13.7 patient-years; 95% confidence interval (CI) = 5.8-21.7], but not female patients (2.9; 95% CI = -4.3 to 10.2); effect modification test, F (1,14) = 4.77; P = 0.046. Exploratory analyses suggest that differences in the intervention's effect on receipt of any OUD treatment in female and male patients, rather than differences in the duration of OUD treatment, may account for findings. There was no significant effect modification by race or ethnic group [effect modification test F (4,44) = 1.50; P = 0.218]. Primary care clinics that implement office-based addiction treatment by nurses increase patient-years of opioid use disorder (OUD) treatment in male but not female patients. Exploratory findings suggest that differences in the proportion of patients treated for OUD, rather than differences in the duration of OUD treatment, account for observed differences across groups.

Issue/problem Management of patients with opioid use disorder commonly includes opioid agonist therapy as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society. Treatment choices in opioid use disorder pharmacotherapy should be based on the needs of the individual and characteristics of medications. Description of the problem The aim was to present the use of pharmacotherapy in the treatment of opioid use disorder in family medicine practice in Zagreb. We collected data from 30 family physician practices, on patients treated for opioid use disorder. We analyzed the epidemiological characteristics of the patient, the diagnosis according to ICD X rev., as well as the frequency of the medication use and the duration of the treatment. Results Data about 100 patients treated for opioid use disorder were obtained, (88% men and 12% women). The average age of the patients was 37.9 years. From all patients, 31% had dg. F.60, 22% had dg. F19, 15% had dg. F32, 3% had dg. F29. 19% of patients was HCV positive. 62%of patients were treated with buprenorphine and 38% with methadone. In 5% of patients buprenorphine was only medication in therapy. 53% of patients with buprenorphine use diazepam, 30% use buprenorphine with antidepressant, and 12% use diazepam and antidepressant with buprenorphine. All patients who are on methadone therapy are using some other medication in therapy. Methadone is commonly prescribed in combination with diazepam and antidepressant (55%). The following combination is methadone and diazepam (34%), a combination of methadone, antipsychotics and pregabalin (7%) and a combination of methadone, antidepressants and antipsychotics (4%). The average duration of treatment for opiate addicts is 11.9 years. Lessons Patients who use buprenorphine in the treatment of opioid use disorder have less need for additional medication in therapy than patients who use methadone. Key messages Patients who use buprenorphine in the treatment of opioid use disorder have less need for additional medication in therapy than patients who use methadone. Treatment choices in opioid use disorder pharmacotherapy should be based on the needs of the individual and characteristics of medications.

The opioid crisis has devasted individuals, families, and communities in the United States and abroad. Improving opioid use disorder (OUD) treatment requires a nuanced understanding of the risk factors associated with the onset of OUD, and barriers to successful, long-term recovery. Women and men might have several unique risk factors for initiating opioid use, progressing from non-medical opioid use to OUD, and experiencing negative OUD treatment outcomes. These unique risk factors are best understood by examining sex as a biological variable and gender as a social construct in persons with OUD. Toward this end, the research reviewed in this chapter includes sex-based biological factors that affect opioid use, such as neurohormonal interactions with the endogenous opioid system and sex-based differences in neural development, as well as gender-based societal influences that can lead to OUD and potentially stymie attempts at treatment, such as traditional gender roles within the family unit and stigma surrounding OUD treatment. Factors that encompass the intersection of sex and gender are also discussed in the context of OUD treatment, including co-morbid mental health conditions, chronic pain, and response to medications for OUD (MOUD). Building on the preclinical and clinical research on these topics, future studies should aim to optimize pharmacotherapeutic approaches within subpopulations of women and men with OUD, develop strategies to better engage women and men with childcare responsibilities in OUD treatment, and reduce stigma associated with living with OUD and seeking treatment for OUD.