Aminoshariae A, JC, Donaldson M et al. (2016). Evidence-based recommendations for analgesic efficacy to treat pain of endodontic origin: A systematic review of randomized controlled trials. J Am Dent Assoc. July 28. Pain of endodontic origin Preoperative and postoperative Various – not well described Various drugs, doses and methods of administration (oral, intramuscular or injection at periapical site) Systematic review of 27 cohort- randomized placebo-controlled trials. Moderate evidence to support nonsteroidal (NSAIDs) preoperatively or postoperatively to control pain of endodontic origin. When NSAIDs were not effective, a combination of NSAIDs with acetaminophen, tramadol, or an opioid appeared beneficial. Authors’ conclusion: NSAIDs should be considered as the drugs of choice to alleviate or minimize pain of endodontic origin if there are no contra-indications for the patient to ingest an NSAID. In situations in which NSAIDs alone are not effective, the combination of an NSAID with acetaminophen or a centrally acting drug is recommended. Steroids appear effective in irreversible pulpitis. This review did not specifically examine the issue of whether low-dose codeine combinations are more effective than the in the combination alone. The authors’ recommendations for adding a centrally acting drug are based on studies that included morphine, tramadol, oxycodone, hydrocodone or high dose codeine (60mg) combinations. This paper does not provide evidence for the incremental analgesic effectiveness of low-dose codeine combination products over the non-opiate in the combination. There was no safety information in the paper. trial inflammatory opiate
given 6 times in 24 hours, followed by 5 doses every four hours. The study abstract indicates that it was a double blind randomised crossover investigation of 26 patients with coxarthrosis and persistent pain. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. The Peloso study was placebo controlled and did not address the issue of incremental effectiveness. The Kjaersgaard-Andersen study looked at the incremental effectiveness of high dose (60mg) codeine and paracetamol. The Quiding study was included in the commissioned review. Neither the da Cochrane review, nor the individual studies mentioned above, provides evidence of the incremental analgesic
effectiveness of low-dose codeine combinations. No new adverse events were identified. Derry S, Karlin SM, Moore RA. (2015) Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database of Systematic Reviews DOI: Acute postoperative pain in adults Area under the pain relief versus time curve. Proportion of patients with at least 50% pain relief over six hours. RR and NNT. Proportion of participants requiring rescue medication and weighted mean of median time to use. Single dose ibuprofen + codeine vs placebo or the same dose of ibuprofen alone Low (<10mg), medium (10-20mg) and high (>20mg) doses of codeine Updated Cochrane review (original 2013) - date of search 1 December 2014. No new studies found. Six studies with 1342 participants In four studies (443 participants) using ibuprofen 400 mg plus codeine 25.6 mg to 60 mg (high dose codeine) 64% of participants had at least 50% maximum pain relief with the combination compared to 18% with placebo. The NNT was 2.2 (95% confidence interval 1.8 to 2.6) (high quality evidence). In three studies (204 participants) ibuprofen plus codeine (any dose) was better than the same dose of ibuprofen (69% versus 55%) but the result was barely significant with a relative benefit of 1.3 The review sought evidence according to the dose of codeine used (low< 10mg, medium 10 to 20mg, and high >20mg). The authors found no data relating to low-dose codeine, limited data for medium dose codeine and most of the data related to high dose codeine (25.6 – 60mg codeine). One study compared ibuprofen 400mg + 20mg codeine with same dose of ibuprofen alone (McQuay 1989) and 2 studies compared ibuprofen 400mg + 60mg codeine with same dose of ibuprofen alone (Cooper 1982 and Sunshine 1987). For these three studies analysed together, ibuprofen plus codeine was better than ibuprofen alone, but the difference only just reached statistical significance (relative benefit 1.3 (1.01 to 1.6)) and the McQuay study (medium
(1.01 to 1.6) (moderate quality evidence). In two studies (159 participants) ibuprofen plus codeine appeared to be better than the same dose of codeine alone (69% versus 33%), but no analysis was done. There was no difference between the combination and placebo in the reporting of adverse events in these acute studies (moderate quality evidence). Authors’ conclusions: The combin-ation of ibuprofen 400 mg plus codeine 25.6 mg to 60 mg demonstrates good analgesic efficacy. Very limited data suggest that the combination is better than the same dose of either drug alone, and that similar numbers of people experience adverse events with the combination as with placebo. dose) had insufficient data to analyse on its own. The McQuay study was included in the commissioned review. This paper does not provide additional evidence for the incremental analgesia effectiveness of low-dose codeine in combination products. The review does not provide detailed safety information. Graudins A, Meek R, D, Parkinson J, Meyer A. (2015) A double blind, randomised controlled comparing single-dose Initial analgesia in adult emergency department patients with moderate pain from limb injury Primary outcome: change in visual analog rating (VAS) from baseline to 30 Single-dose of oral paracetamol + ibuprofen + thiamine DBRCT – three arm 182 adult patients from 18 to 75 years with isolated limb injury and moderate pain (VAS greater than 3 Conference abstract only. Abstract submitted to the 31st Annual Scientific Meeting of the Australasian College for Emergency
Secondary outcomes: adverse events; days in hospital; readmission to hospital. placebo/no treatment); opioids vs non opioids, opioids vs combinations and non-opioids vs combinations women, contributed data to the analysis. Authors considered only 4 of the 8 trials were of high quality. All trials were small. There was insufficient evidence to establish analgesic effects. were more side effects, including nausea, vomiting and drowsiness, with the use of an opioid, non-opioid or combination painkillers in comparison with placebo or no treatment. Authors’ conclusion: Due to limited data available no conclusions can be made regarding the safest and most effective forms of oral analgesia for pain. paracetamol 1000mg (50 women) with a combination of submaximal dose of paracetamol 800 mg + codeine 60mg (50 women), and placebo (25 women). The abstract of this indicates that, in patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables. As this study used 60mg of codeine it does not provide evidence of incremental effectiveness of low-dose codeine. R. A., et al. (2015a) (OTC) oral analgesics for acute pain - an overview of Cochrane reviews. Cochrane Database of Systematic Reviews DOI: Acute pain (generally post-operative pain after third molar extraction) Primary outcome = number of participants with at least 50% pain relief over four to six hours Over-the-counter (OTC) analgesics vs placebo Overview of 1 and 10 Cochrane reviews involving 21 different analgesic products. The authors indicate that they found no data for OTC analgesics combining a low The authors considered that “combination products with low doses of codeine represent the major gap in the evidence, but probably represent a large part of OTC analgesic sales. The lack of any information on the efficacy of low dose codeine caesarean prescription
Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, Straube S. (2014) Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database of Systematic Reviews Issue 9. Art. No.: CD006601. Cancer pain due to diverse types of malignancy in adults (no studies in children identified) Various measures of efficacy and adverse events Only two studies reported the preferred responder outcome of “participants with at least 50% reduction in pain” and two reported “participants with no worse than mild pain Single or multiple doses of codeine with and without paracetamol compared to placebo or alternative actives Any formulation, dosage regimen and route of administration. Cochrane review of RDBCTs 15 studies with 721 participants with cancer pain. Most studies used codeine at doses of 30mg to 120mg The authors noted that • all but one of the studies demonstrated superiority of codeine over placebo in at one outcome measure • there were insufficient data for any pooled analysis • adverse event reporting was poor • the literature was disappointing - studies were of short duration, and most had significant shortcomings in reporting. Authors’ conclusion: The available evidence indicates that codeine is more effective against cancer pain than placebo, but with increased risk of nausea, vomiting, and constipation. None of the included studies compared codeine containing combinations with the non-opiate in the combination. One included study (Chen 2003) was a three arm crossover study in 18 people with moderate to severe cancer pain. The study compared single dose codeine 30mg (C), placebo (P) and codeine 13mg + ibuprofen 200mg (CI). Partial or complete pain relief was achieved in 18/18 with C and 17/18 with CI. Time to showing effect was less with CI than with C (48mins vs 60mins) and was main-tained for longer (6.8 hours vs 5.4 hours). the Chen study gives some limited low quality evidence for analgesic effectiveness of low dose codeine in combination with ibuprofen, it did not include an ibuprofen only arm and the incremental analgesic effectiveness of the codeine in this combination could not be assessed. trial