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      Opioids for Chronic Noncancer Pain : A Systematic Review and Meta-analysis

      1 , 2 , 3 , 4 , 1 , 2 , 5 , 6 , 3 , 3 , 7 , 8 , 3 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 1 , 3 , 16 , 17 , 17 , 3 , 18 , 1 , 19 , 20 , 21 , 3 , 22 , 3 , 23 , 24 , 2 , 25 , 3 , 1 , 26 , 1 , 27 , 28 , 3 , 3 , 29 , 24 , 3 , 5 , 1 , 2 , 30 , 3

      JAMA

      American Medical Association (AMA)

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          Abstract

          Harms and benefits of opioids for chronic noncancer pain remain unclear.

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          Most cited references 72

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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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            The promotion and marketing of oxycontin: commercial triumph, public health tragedy.

            I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues. Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a positive impact on the public health.
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              Morphine, gabapentin, or their combination for neuropathic pain.

              The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia. In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life. Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05). Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Journal
                JAMA
                JAMA
                American Medical Association (AMA)
                0098-7484
                December 18 2018
                December 18 2018
                : 320
                : 23
                : 2448
                Affiliations
                [1 ]Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
                [2 ]Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
                [3 ]Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
                [4 ]Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada
                [5 ]Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu
                [6 ]Faculty of Medicine, Ain Shams University, Cairo, Egypt
                [7 ]Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
                [8 ]Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
                [9 ]Now with the Canadian Agency for Drugs and Technologies in Health (CADTH), Toronto, Ontario, Canada
                [10 ]Pharmaceutical Science, University of Sorocaba, Sao Paulo, Brazil
                [11 ]Leonardo Hirslanden Klinik Birshof, Münchenstein, Switzerland
                [12 ]Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
                [13 ]Department of Internal Medicine, Hospital Alemán de Buenos Aires, Buenos Aires, Argentina
                [14 ]Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Ontario, Canada
                [15 ]Department of Anesthesiology, Perioperative and Pain Medicine, University of Calgary, Calgary, Alberta, Canada
                [16 ]Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
                [17 ]Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada
                [18 ]Department of Medicine, University of Toronto, Toronto, Ontario, Canada
                [19 ]Accident and Emergency Department, Queen Mary Hospital, Pokfulam, Hong Kong, China
                [20 ]Accident and Emergency Department, Tuen Mun Hospital, Hong Kong, China
                [21 ]Department of Medicine, Gjøvik, Innlandet Hospital Trust, Norway
                [22 ]Department of Hygiene and Dietetics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
                [23 ]Institute for Clinical Epidemiology and Biostatistics, University of Basel Hospital, Basel, Switzerland
                [24 ]Department of Clinical Research, University of Basel Hospital, Basel, Switzerland.
                [25 ]Department of Anesthesiology, Operative Intensive Care, Preclinical Emergency Medicine and Pain Management, University of Basel Hospital, Basel, Switzerland
                [26 ]Isfahan Medical Education Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
                [27 ]Canadian Academy of Osteopathy, Hamilton, Ontario, Canada
                [28 ]Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
                [29 ]Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
                [30 ]Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio
                Article
                10.1001/jama.2018.18472
                6583638
                30561481
                © 2018

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