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      Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method

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          Abstract

          Background

          Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use.

          Cases

          We present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms.

          Discussion

          Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction.

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          Most cited references23

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          Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

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            A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

            Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised, double-blinded study evaluated the analgesic efficacy of prolonged-release (PR) oral oxycodone when co-administered with PR oral naloxone, and its impact on opioid-induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone. A total of 202 patients with chronic pain (mainly non-cancer related, 2.5% of patients had cancer-related pain) under stable oral oxycodone therapy (40, 60 or 80 mg/day) were randomised to receive 10, 20, 40 mg/day naloxone or placebo. After a 4-week maintenance phase, patients received oxycodone only for 2 weeks. Pain intensity was evaluated using a numerical analogue scale and bowel function was assessed using the bowel function index. No loss of analgesic efficacy with naloxone was observed. Mean pain intensity scores on randomisation were comparable for placebo, 10mg, 20mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo (p<0.05). Overall, the combination was well tolerated, with no unexpected adverse events. There was a trend towards an increased incidence of diarrhoea with higher doses of naloxone. The 2:1 oxycodone/naloxone ratio was identified as the most suitable for further development. Co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.
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              Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse.

              Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use. A total of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report. There were significant effects of maintenance treatment on rates of illicit opioid use, but no significant differences in treatment retention or the rates of cocaine use. The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments. The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use, but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use.
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                Author and article information

                Journal
                Subst Abuse Rehabil
                Subst Abuse Rehabil
                Substance Abuse and Rehabilitation
                Substance Abuse and Rehabilitation
                Dove Medical Press
                1179-8467
                2016
                20 July 2016
                : 7
                : 99-105
                Affiliations
                [1 ]Division of Addiction, University Psychiatric Services Bern, Bern, Switzerland
                [2 ]Division of Substance Use and Addictive Disorders, University of Basel Psychiatric Hospital, Basel, Switzerland
                Author notes
                Correspondence: Marc Vogel, Division of Substance Use and Addictive Disorders, University of Basel Psychiatric Hospital, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland, Tel +41 61 325 5111, Fax +41 61 325 5583, Email Marc.Vogel@ 123456upkbs.ch
                Article
                sar-7-099
                10.2147/SAR.S109919
                4959756
                27499655
                bea793b3-7495-474f-bf93-e722c32bc4e3
                © 2016 Hämmig et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                subutex,suboxone,heroin,opiate,substitution
                subutex, suboxone, heroin, opiate, substitution

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