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      Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

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          Abstract

          Background and Objectives

          Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA‐approved medications is an evidence‐based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone‐based relapse‐prevention treatment.

          Methods

          Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone.

          Results

          Emerging practices for extended‐release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences.

          Conclusions and Scientific Significance

          Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended‐release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177–187)

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          Most cited references101

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          Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis.

          Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from <1% to 81% across studies. Across most calculations, rates of misuse averaged between 21% and 29% (range, 95% confidence interval [CI]: 13%-38%). Rates of addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
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            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.
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              Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial.

              No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone. Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.
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                Author and article information

                Contributors
                adam.bisaga@nyspi.columbia.edu
                Journal
                Am J Addict
                Am J Addict
                10.1111/(ISSN)1521-0391
                AJAD
                The American Journal on Addictions
                John Wiley and Sons Inc. (Hoboken )
                1055-0496
                1521-0391
                29 March 2018
                April 2018
                : 27
                : 3 ( doiID: 10.1111/ajad.v27.3 )
                : 177-187
                Affiliations
                [ 1 ] Department of Psychiatry Columbia University College of Physicians and Surgeons New York New York
                [ 2 ] Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina
                [ 3 ] Alkermes Inc. Waltham Massachusetts
                [ 4 ] Scientific Consultant Edgewater New Jersey
                [ 5 ] Department of Family and Community Health School of Nursing University of Pennsylvania Philadelphia Pennsylvania
                [ 6 ] Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania
                [ 7 ] Baylor College of Medicine Houston Texas
                Author notes
                [*] [* ] Address correspondence to Dr. Bisaga, Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, 1051 Riverside Dr., Unit #120, New York, NY 10032.

                E‐mail: adam.bisaga@ 123456nyspi.columbia.edu

                Author information
                http://orcid.org/0000-0003-1415-5436
                http://orcid.org/0000-0002-7834-6138
                Article
                AJAD12711
                10.1111/ajad.12711
                5900907
                29596725
                971593cb-a796-43c0-9f5c-a85f182d37a9
                © 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP)

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 08 September 2017
                : 02 March 2018
                : 03 March 2018
                Page count
                Figures: 1, Tables: 2, Pages: 11, Words: 7867
                Funding
                Funded by: Alkermes Inc.
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                ajad12711
                April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.4 mode:remove_FC converted:16.04.2018

                Health & Social care
                Health & Social care

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