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      Advances in the treatment of opioid use disorders

      review-article
      a , 1
      F1000Research
      F1000Research
      naltrexone, buprenorphine, opioid use disorders, methadone, substance abuse, heroin

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          Abstract

          The development of medications for treating persons with opioid use disorders has expanded the number of evidence-based treatment options, particularly for persons with the most severe disorders. It has also improved outcomes compared to psychosocial treatment alone and expanded treatment availability by increasing the number of physicians involved in treatment and the settings where patients can be treated. The medications include methadone, buprenorphine, buprenorphine/naloxone, and extended-release injectable naltrexone. Studies have shown that they are most effective when used over an extended, but as-yet-unspecified, period of time and with counseling and other services, particularly for the many with psychosocial problems. Though controversial in some cultures, well-designed studies in Switzerland, the Netherlands, Germany, and Canada have demonstrated the efficacy of supervised heroin injecting for persons who responded poorly to other treatments, and this treatment option has been approved by Switzerland and a few other E.U. countries. The degree to which medication-assisted therapies are available is dependent on many variables, including national and local regulations, preferences of individual providers and their geographical location, treatment costs, and insurance policies. Greater availability of medication-assisted therapies has become a major focus in the U.S. and Canada, where there has been a marked increase in deaths associated with heroin and prescription opioid use. This paper provides a brief summary of these developments.

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          Most cited references24

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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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            Clinical pharmacology of buprenorphine: ceiling effects at high doses.

            The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial mu-agonist, across a wide range of doses in comparison to methadone. Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration. Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range. This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.
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              What is recovery? A working definition from the Betty Ford Institute.

              (2007)
              There is an unknown but very large number of individuals who have experienced and successfully resolved dependence on alcohol or other drugs. These individuals refer to their new sober and productive lifestyle as "recovery." Although widely used, the lack of a standard definition for this term has hindered public understanding and research on the topic that might foster more and better recovery-oriented interventions. To this end, a group of interested researchers, treatment providers, recovery advocates, and policymakers was convened by the Betty Ford Institute to develop an initial definition of recovery as a starting point for better communication, research, and public understanding. Recovery is defined in this article as a voluntarily maintained lifestyle composed characterized by sobriety, personal health, and citizenship. This article presents the operational definitions, rationales, and research implications for each of the three elements of this definition.
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                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                27 January 2017
                2017
                : 6
                : 87
                Affiliations
                [1 ]Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 3440 Market Street, 3rd Floor, Philadelphia, USA
                Author notes

                Competing interests: The author declares that he has no competing interests.

                Author information
                http://orcid.org/0000-0003-2352-3800
                Article
                10.12688/f1000research.10184.1
                5288680
                93bf69d9-be09-4f5b-a631-5896eab67905
                Copyright: © 2017 Woody GE

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2017
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles
                Health Systems & Services Research
                Social & Behavioral Determinants of Health
                Substance Abuse

                naltrexone,buprenorphine,opioid use disorders,methadone,substance abuse,heroin

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