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8 Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of ran- domised trials of oral opioids Moore R and McQuay H. Arthritis Research andTherapy 2005; 7:R1045-51 This meta analysis was designed to establish prevalence rates for oral opioid use in chronic non-cancer pain of different aetiology and also to investigate any major differences in opioid adverse events. Thirty-four trials with 5,546 patients were included with 4,212 patients contributing some information on opioid adverse events. Ninety percent of the patients studied were suffering from moderate rather than severe pain. The use of any oral opioid produced higher rates of adverse events than did placebo. 51% of patients experienced at least one adverse event. There was no obvious relationship between high or low rates of adverse events and drug, dose, or dosing regimen. Different painful conditions produced comparable result patterns. A high proportion of those patients on opioids (22%) discontinued treatment due to the adverse events whereas only 6,5 % withdrew because of lack of efficacy. Because of the relatively short duration of these trials (less than 4 weeks) and limited use of dose titration these results have limited applicability for longer-term opioid use in clinical practice. Future trials should be designed to consider a number of crucial variables including dose and duration of treatment as initial adverse events may improve with time. SUMMARY OF PUBLICATIONS Opioids in chronic non-cancer pain: systematic review of efficacy and safety Kalso E, Edwards J, Moore R, McQuay H. Pain, 2004, 112:372-390 Controversy exists about the effectiveness of opioids for treatment of certain types of chronic pain e.g. neuropathic pain and also their safety with long-term use. This study has analysed available randomised, placebo-controlled efficacy and safety trials of WHO step 3 opioids from various databases until September 2003. Inclusion criteria were randomised comparisons of oral, transdermal or intravenous WHO step 3 opioids with placebo in chronic non-cancer pain. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. Adverse events prevented many patients from increasing the opioid dose to the maximum allowed to improve pain relief. About 80% of patients experienced at least one adverse event; constipation (41%), nausea (32%) and somnolence (29%) were most commonly encountered. 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 all pain conditions. However, only a minority of patients in these studies went on to long-term treatment. The relatively small number of patients studied and the short follow-ups times limit any conclusions that can be drawn concerning problems such as tolerance and addiction. Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mech- anisms, implications, and man- agement options Porreca F and Ossipov M. Pain Medicine 2009; March 19 One of the major reasons for discon- tinuation of opioid analgesic treat- ment in patients treated with opioids for chronic pain is side- ef- fects such as nausea and vomiting. These have a negative effect on treatment efficacy and successful patient management because they limit the effective analgesic dosage that can be achieved. A number of mechanisms by which opioids produce nausea and vomit- ing have been identified, involving both central and peripheral sites. The effects are mediated via interac- tion with specific opioid receptors (mu, delta, and kappa subtypes) in the brain and spinal cord and some- times at peripheral sites. Strategies to control nausea and vomiting in- clude the use of antiemetic drugs and also opioid switching, neither of which is ideal, as they are not always effective and incur additional costs. One novel approach to the problem is to combine more than one anal- gesic principle in one molecule so that the drug has two analgesic modes of action. This concept has been realised in tapentadol which combines mu opioid receptor ago- nist activity with norepinephrine re- uptake inhibition. Preclinical studies have indicated that this combination of two analgesic actions is less likely to produce opioid-induced side effects and thus help to alleviate this problem.