Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety

University of Oxford, Oxford, England, United Kingdom
Pain (Impact Factor: 5.21). 01/2005; 112(3):372-80. DOI: 10.1016/j.pain.2004.09.019
Source: PubMed


Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

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    • "Furthermore, randomised controlled trials have provided mixed results regarding functional improvement during opioid therapy. While some reviews have concluded that alternative drugs produce better functional outcomes when compared to opioids [22], others have reported inconclusive results [29] [32] [39]. "
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    ABSTRACT: With increasing concerns about the potential harm of long-term opioid therapy, there is a need for the development and implementation of alternative treatment strategies for patients with chronic pain who have been using opioids for a prolonged period of time. Based on the findings from a recent qualitative investigation that suggested there may be a bidirectional association between opioid reliance and habitual overactivity behaviour (activity engagement that significantly exacerbates pain), this study was designed to quantitatively investigate the association between opioid use and habitual overactivity over a five-day period in a group of chronic pain patients. Participants provided a list of their prescribed pain medication, completed a self-report measure of habitual overactivity, and then commenced five days of data collection. Data collection required participants to wear an activity monitor and to complete a diary that detailed their daily activities and the time they took medication. Individuals reporting higher levels of habitual overactivity were more likely to be prescribed opioids. In addition, higher levels of habitual overactivity were associated with more frequent "as needed" (PRN) opioid use over the five days, and with a discrepancy between the prescribed and actual oral Morphine-Equivalent Daily Dose (oMEDD), where more medication was taken than was prescribed. There was no predominant context for PRN use. The results of this study support the idea that habitual overactivity behaviour may play a role in the development of a reliance on opioid medication, and that such an association may provide a potential treatment target for opioid therapy rationalisation.
    No preview · Article · Oct 2015 · Pain
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    • "Opioid-induced constipation (OIC) is common in patients treated with opioids for moderate or severe pain [1]. The estimated prevalence of OIC ranges between 15 and 90% in patients receiving opioids for noncancer pain [2]. "
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    ABSTRACT: To characterize the absorption, distribution, metabolism, and excretion of naloxegol, a PEGylated derivative of the µ-opioid antagonist naloxone, in healthy male subjects. [14C]-Labeled naloxegol (27 mg, 3.43 MBq) was administered as an oral solution to 6 fasted subjects. Blood, fecal, and urine samples were collected predose and at various intervals postdose. Naloxegol and its metabolites were quantified or identified by liquid chromatography with radiometric or mass spectrometric detection. Pharmacokinetic parameters were calculated for each subject, and metabolite identification was performed by liquid chromatography with parallel radioactivity measurement and mass spectrometry. Naloxegol was rapidly absorbed, with a maximum plasma concentration (geometric mean) of 51 ng/mL reached before 2 hours after dosing. A second peak in the observed naloxegol and [14C] plasma concentration-time profiles was observed at ~ 3 hours and was likely due to enterohepatic recycling of parent naloxegol. Distribution to red blood cells was negligible. Metabolism of [14C]-naloxegol was rapid and extensive and occurred via demethylation and oxidation, dealkylation, and shortening of the polyethylene glycol chain. Mean cumulative recovery of radioactivity was 84.2% of the total dose, with ~ 68.9% recovered within 96 hours of dosing. Fecal excretion was the predominant route of elimination, with mean recoveries of total radioactivity in feces and urine of 67.7% and 16.0%, respectively. Unchanged naloxegol accounted for ~ 1/4 of the radioactivity recovered in feces. Naloxegol was rapidly absorbed and cleared via metabolism, with predominantly fecal excretion of parent and metabolites.
    Full-text · Article · Sep 2015 · International journal of clinical pharmacology and therapeutics
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    • "The central blockade of opioid receptors provides the analgesic property of opioids, but the peripheral blockade that doesn't contribute much to analgesia leads to a variety of side effects instead [3] [5] [6]. With the dramatic increase in opioid use in recent years, the incidence of opioidinduced side effects has also seen a momentous increase [7] [8]. "
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    ABSTRACT: Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and bear pain instead of OIC. Laxatives have commonly been used as a prophylaxis and treatment of OIC but they are frequently ineffective because the commonly available laxatives do not target the underlying mechanism of OIC, which is the blockade of peripheral mu-receptors. Recently, there have been a number of advances in the treatment of OIC, which any physician involved with opioid-prescribing discipline should be aware of. This review will update the new options and strategies available for treating OIC along with the relevant clinical trials. Finally, this review also provides a recommendation on the preferred way to approach a patient with OIC in the modern era as well as highlight on the importance of doctor-patient communication in this setting.
    Full-text · Article · Jun 2015 · Scandinavian Journal of Gastroenterology
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