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      Chronic use of tramadol after acute pain episode: cohort study

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          Abstract

          Objective

          To determine the risk of prolonged opioid use in patients receiving tramadol compared with other short acting opioids.

          Design

          Observational study of administrative claims data.

          Setting

          United States commercial and Medicare Advantage insurance claims (OptumLabs Data Warehouse) January 1, 2009 through June 30, 2018.

          Participants

          Opioid-naive patients undergoing elective surgery.

          Main outcome measure

          Risk of persistent opioid use after discharge for patients treated with tramadol alone compared with other short acting opioids, using three commonly used definitions of prolonged opioid use from the literature: additional opioid use (defined as at least one opioid fill 90-180 days after surgery); persistent opioid use (any span of opioid use starting in the 180 days after surgery and lasting ≥90 days); and CONSORT definition (an opioid use episode starting in the 180 days after surgery that spans ≥90 days and includes either ≥10 opioid fills or ≥120 days’ supply of opioids).

          Results

          Of 444 764 patients who met the inclusion criteria, 357 884 filled a discharge prescription for one or more opioids associated with one of 20 included operations. The most commonly prescribed post-surgery opioid was hydrocodone (53.0% of those filling a single opioid), followed by short acting oxycodone (37.5%) and tramadol (4.0%). The unadjusted risk of prolonged opioid use after surgery was 7.1% (n=31 431) with additional opioid use, 1.0% (n=4457) with persistent opioid use, and 0.5% (n=2027) meeting the CONSORT definition. Receipt of tramadol alone was associated with a 6% increase in the risk of additional opioid use relative to people receiving other short acting opioids (incidence rate ratio 95% confidence interval 1.00 to 1.13; risk difference 0.5 percentage points; P=0.049), 47% increase in the adjusted risk of persistent opioid use (1.25 to 1.69; 0.5 percentage points; P<0.001), and 41% increase in the adjusted risk of a CONSORT chronic opioid use episode (1.08 to 1.75; 0.2 percentage points; P=0.013).

          Conclusions

          People receiving tramadol alone after surgery had similar to somewhat higher risks of prolonged opioid use compared with those receiving other short acting opioids. Federal governing bodies should consider reclassifying tramadol, and providers should use as much caution when prescribing tramadol in the setting of acute pain as for other short acting opioids.

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          Most cited references37

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          Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain

          Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.
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            • Abstract: not found
            • Article: not found

            Clinical Pharmacology of Tramadol

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              Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

              Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects. The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers. Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and important drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes. This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.
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                Author and article information

                Contributors
                Role: assistant professor of health services research
                Role: professor of health services research
                Role: professor of anesthesiology
                Role: research associateRole: visiting fellow
                Journal
                BMJ
                BMJ
                BMJ-US
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2019
                14 May 2019
                : 365
                : l1849
                Affiliations
                [1 ]Department of Surgery, Mayo Clinic, Rochester, MN, USA
                [2 ]Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery and Department of Health Services Research, Mayo Clinic, Rochester, MN 55905, USA
                [3 ]Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA
                [4 ]OptumLabs, Cambridge, MA 02142, USA
                Author notes
                Correspondence to: M M Jeffery Jeffery.Molly@ 123456mayo.edu or @MollyJeffery on Twitter
                Author information
                https://orcid.org/0000-0003-3854-6810
                Article
                thic048304
                10.1136/bmj.l1849
                6514531
                31088782
                9f66a9da-80e6-450b-b6b6-12b6cd1fcbc9
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 25 March 2019
                Categories
                Research
                1779

                Medicine
                Medicine

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