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      Toward a systematic approach to opioid rotation

      1 , 2 , 3

      Journal of Pain Research

      Dove Medical Press

      chronic pain, opioid rotation, opioid analgesics

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          Abstract

          Patients requiring chronic opioid therapy may not respond to or tolerate the first opioid prescribed to them, necessitating rotation to another opioid. They may also require dose increases for a number of reasons, including worsening disease and increased pain. Dose escalation to restore analgesia using the primary opioid may lead to increased adverse events. In these patients, rotation to a different opioid at a lower-than-equivalent dose may be sufficient to maintain adequate tolerability and analgesia. In published trials and case series, opioid rotation is performed either using a predetermined substitute opioid with fixed conversion methods, or in a manner that appears to be no more systematic than trial and error. In clinical practice, opioid rotation must be performed with consideration of individual patient characteristics, comorbidities (eg, concurrent psychiatric, pulmonary, renal, or hepatic illness), and concurrent medications, using flexible dosing protocols that take into account incomplete opioid cross-tolerance. References cited in this review were identified via a search of PubMed covering all English language publications up to May 21, 2013 pertaining to opioid rotation, excluding narrative reviews, letters, and expert opinion. The search yielded a total of 129 articles, 92 of which were judged to provide relevant information and subsequently included in this review. Through a review of this literature and from the authors’ empiric experience, this review provides practical information on performing opioid rotation in clinical practice.

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          Most cited references 135

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          Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.

          Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.
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            Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.

             Richard P. Mattick (corresponding) ,  Courtney Breen,  Jo Kimber (2009)
            Methadone maintenance was the first widely used opioid replacement therapy to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed. To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence. We searched the following databases up to Dec 2008: the Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs. All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. Reviewers evaluated the papers separately and independently, rating methodological quality of sequence generation, concealment of allocation and bias. Data were extracted independently for meta-analysis and double-entered. Eleven studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 1969 participants. The sequence generation was inadequate in one study, adequate in five studies and unclear in the remaining studies. The allocation of concealment was adequate in three studies and unclear in the remaining studies. Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25) or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39). Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity or mortality.
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              Molecular mechanisms of opioid receptor-dependent signaling and behavior.

              Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibitory G proteins. These receptors form homo- and heterodimeric complexes and signal to kinase cascades and scaffold a variety of proteins.The authors discuss classic mechanisms and developments in understanding opioid tolerance and opioid receptor signaling and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. The authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, the authors conclude there is a continued need for more translational work on opioid receptors in vivo.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2014
                17 October 2014
                : 7
                : 589-608
                Affiliations
                [1 ]Department of Anesthesiology, Albany Medical College, Albany, NY, USA
                [2 ]Global Scientific Affairs, Mallinckrodt Pharmaceuticals, St Louis, MO, USA
                [3 ]Center for Bioethics, Pain Management and Medicine, St Louis, MO, USA
                Author notes
                Correspondence: John F Peppin, Center for Bioethics, Pain Management and Medicine, 8013 Presidio Court, University City, MO, 63130, USA, Tel +1 859 221 3154, Email johnpeppin@ 123456msn.com
                [†]

                Author deceased May 18, 2013

                Article
                jpr-7-589
                10.2147/JPR.S55782
                4207581
                © 2014 Smith and Peppin. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Anesthesiology & Pain management

                opioid analgesics, opioid rotation, chronic pain

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