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Broad synthesis / Overview of systematic reviews

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Zeitung Cochrane Database of Systematic Reviews
Year 2015
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BACKGROUND: Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. OBJECTIVES: To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain. METHODS: We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions. We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo. MAIN RESULTS: We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations. The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo. AUTHORS' CONCLUSIONS: There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.

Broad synthesis

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Zeitung Acta anaesthesiologica Scandinavica
Year 2014
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Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.