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The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in 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 the number of participants with at least 50% pain relief over four to six hours compared with placebo. For 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 the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3 -
The Cochrane Database of Systematic... Sep 2015A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the μ-opioid receptor and inhibiting noradrenaline reuptake. The efficacy of tapentadol is stated to be comparable to morphine and oxycodone.
OBJECTIVES
To assess the analgesic efficacy of tapentadol for the relief of cancer pain in adults, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from January 2005 to July 2015, together with reference lists of retrieved papers and review articles, and two clinical trial registries. Searches started from 2005 because this covered the period during which clinical trials were conducted. We contacted the manufacturer of tapentadol in the UK to find additional trials not identified by electronic searches. We did not restrict searches by language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of tapentadol compared with placebo or active controls in adults with moderate to severe cancer pain. Pain had to be measured using a validated assessment tool, and studies had to include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standard form and assessed risk of bias. We extracted available data on study design, participant details, interventions, and outcomes, including analgesic outcome measures, withdrawals, and adverse events.
MAIN RESULTS
We included four studies with 1029 participants. All the studies used a parallel-group design, and included an initial titration phase to determine the maximum effective and tolerated dose, followed by a maintenance phase. Tapentadol medication was taken twice daily and doses ranged from 50 to 500 mg per day. Rescue medication (morphine or oxycodone immediate-release) was available to participants in all studies.Overall, 440 participants were randomised in classically designed RCTs, and 589 participants were enrolled in enriched-enrolment, randomised-withdrawal (EERW) trials. A total of 476 participants were randomised to titration with tapentadol and 338 participants took tapentadol throughout the maintenance phase of their trial.All studies used numerical rating scores, Patient Global Impression of Change scores, and use of rescue medication as measures of efficacy, and all reported on adverse events and withdrawals.All studies enrolled fewer than 200 participants per treatment arm and were therefore at risk of overestimating efficacy. One study was terminated early due to problems with supply of rescue medication, with fewer than 20 participants enrolled per treatment arm in the maintenance phase of the trial. We judged another study at high risk of bias due to an open-label design.There were insufficient data for pooling and statistical analysis. Response rates for pain intensity were comparable across treatment groups in each study. In one EERW study, response rates were high across both treatment and placebo arms during the maintenance phase (62% tapentadol, 69% morphine, 50% placebo). For pain relief, tapentadol is no more and no less effective than oxycodone or morphine (low quality evidence).Treatment emergent adverse event rates were high, approximately 50% to 90%. The most common adverse events were gastrointestinal (nausea, vomiting, constipation) (low quality evidence). There was no advantage of tapentadol over morphine or oxycodone in terms of serious adverse events. The number of people experiencing effects on consciousness, appetite, or thirst was low.
AUTHORS' CONCLUSIONS
Information from RCTs on the effectiveness and tolerability of tapentadol was limited. The available studies were of moderate or small size and used different designs, which prevented pooling of data. Pain relief and adverse events were comparable between the tapentadol and morphine and oxycodone groups.
Topics: Adult; Humans; Neoplasms; Pain; Phenols; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Tapentadol
PubMed: 26403220
DOI: 10.1002/14651858.CD011460.pub2 -
Pain Physician 2015Canada has featured the second-highest levels of prescription opioid (PO) use globally behind the United States, and reported extensive PO-related harms (e.g.,... (Review)
Review
BACKGROUND
Canada has featured the second-highest levels of prescription opioid (PO) use globally behind the United States, and reported extensive PO-related harms (e.g., non-medical PO use [NMPOU], PO-related morbidity and mortality). A recent comprehensive review synthesized key data on PO use, PO-related harms, and interventions in Canada, yet a substantive extent of new studies and data have emerged.
OBJECTIVE
To conduct and present a comprehensive review update on PO use, PO-related harms, and interventions in Canada since 2010.
STUDY DESIGN
Narrative review
METHODS
We conducted literature searches, employing pertinent keywords, in key databases, focusing on PO-related studies/data in/for Canada since 2010, or pertinent studies/data from earlier periods not included in our previous review. In addition, we identified relevant data from "grey" literature (e.g., government, survey, other data or system reports). Relevant data were screened and extracted, and categorized into 4 main sections of indicators: 1) PO dispensing and use, 2) non-medical PO use, 3) PO-related morbidity/mortality, 4) PO-related interventions and impacts.
RESULTS
PO-dispensing in Canada overall continued to increase and/or remain at high levels in Canada from 2010 to 2013, with the exception of the province of Ontario where marked declines occurred starting in2012; quantitative and qualitative PO dispensing patterns continued to vary considerably between provinces. Several studies identified common "high PO dosing" prescribing practices in different settings. Various data suggested declining NMPOU levels throughout most general (e.g., adult, students), yet not in special risk (e.g., street drug users, First Nations) populations. While treatment demand in Ontario plateaued, rising PO-related driving risks as well as neo-natal morbidity were identified by different studies. PO-related mortality was measured to increase--in total numbers and proportionally--in various Canadian jurisdictions. Select reductions in general PO and/or high-dose PO dispensing were observed following key interventions (e.g., Oxycodone delisting, prescription monitoring program [PMP] introduction in Ontario/British Columbia). While physician education intervention studied indicated mixed outcomes, media reporting was found to be associated with PO prescribing patterns.
LIMITATIONS
The present review did not utilize systematic review standards or meta-analytic techniques given the large heterogeneity of data and outcomes reviewed.
CONCLUSIONS
Recently emerging data help to better characterize PO-related use, harm and intervention indicators in Canada's general context of comparatively high-level PO dispensing and harms, yet major gaps in monitoring and information persist; this continues to be a problematic challenge, especially given the implementation of key PO-related interventions post-2010, the impact of which needs to be properly measured and understood.
Topics: Analgesics, Opioid; Canada; Drug Prescriptions; Drug Utilization; Humans; Opioid-Related Disorders
PubMed: 26218951
DOI: No ID Found -
PloS One 2015To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question "which analgesic combination and dosage is potentially... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question "which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?".
MATERIALS AND METHODS
A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review.
RESULTS
Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 - 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects.
CONCLUSION
This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study.
Topics: Analgesics; Drug Combinations; Humans; Molar, Third; Pain, Postoperative; Treatment Outcome
PubMed: 26053953
DOI: 10.1371/journal.pone.0127611 -
The Journal of Pain Oct 2015Data on the tolerability of opioids in patients with cancer-related pain are limited. Here, we report a systematic review that includes all published prospective studies... (Review)
Review
UNLABELLED
Data on the tolerability of opioids in patients with cancer-related pain are limited. Here, we report a systematic review that includes all published prospective studies reporting adverse events (AEs) of morphine, oxycodone, fentanyl, methadone, or hydromorphone for cancer-related pain in patients naive for these opioids. We included 25 studies describing 31 treatment cohorts, made an overview of study characteristics, and reported rates of AEs per type of opioid. The frequency of the most commonly reported AEs varied widely: nausea from 3 to 85%, vomiting from 4 to 50%, constipation from 5 to 97%, drowsiness from 3 to 88%, and dry mouth from 1 to 94%. There was a large heterogeneity among included studies, especially regarding the assessment and reporting of AEs. We describe how differences in assessment and reporting influence outcome rates. Although AEs are an important issue in daily clinical practice, realistic incidence rates of AEs per type of opioid are unknown because of the immense heterogeneity among studies.
PERSPECTIVE
Although opioid-related adverse events are an important issue when treating cancer-related pain, realistic rates of adverse events per type of opioid are unknown because of immense heterogeneity among studies and lack of systematic assessment and reporting. There is an urgent need for studies with standardized outcome measures and reporting.
Topics: Analgesics, Opioid; Drug-Related Side Effects and Adverse Reactions; Humans; Neoplasms; Outcome Assessment, Health Care; Pain; Prospective Studies
PubMed: 26051219
DOI: 10.1016/j.jpain.2015.05.006 -
The Cochrane Database of Systematic... May 2015Chronic musculoskeletal pain is a prevalent condition and a major cause of disability and absence from the workplace worldwide. Opioids are frequently used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic musculoskeletal pain is a prevalent condition and a major cause of disability and absence from the workplace worldwide. Opioids are frequently used to treat chronic pain, although adverse effects often restrict their long-term benefits. Tapentadol is an opioid and norepinephrine re-uptake inhibitor, which may cause a lower incidence (and severity) of adverse effects compared to other strong opioids.
OBJECTIVES
To determine the efficacy, safety and tolerability of tapentadol extended release for moderate-to-severe pain for at least three months for any musculoskeletal cause.
SEARCH METHODS
We searched electronic databases (CENTRAL, MEDLINE, EMBASE, Web of Science) to March 2014, unrestricted by language, as well as trials registers and reference lists from retrieved studies. We contacted drug manufacturers for further information.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of tapentadol in people with chronic musculoskeletal pain, compared to placebo or active control.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed risk of bias of included studies and extracted data. We performed two meta-analyses for the comparisons tapentadol extended release vs. placebo, and tapentadol extended release vs. active-control (oxycodone). We used random-effects and fixed-effect models according to the presence or not of heterogeneity, respectively. Also, we performed subgroup analyses. The primary efficacy outcome was pain control assessed by change in pain intensity scores and responder's rate (at least 50% pain relief). Primary safety outcome was withdrawal rate due to adverse effects.
MAIN RESULTS
Four parallel-design RCTs of moderate quality including 4094 patients with osteoarthritis or back pain, or both, met the inclusion criteria. Three trials were phase III studies with 12-weeks follow-up and the fourth trial was an open-label safety study of 52-weeks follow-up. All trials were oxycodone-controlled and three were also placebo-controlled. Two trials included patients with knee osteoarthritis, one evaluated patients with low back pain and one enrolled both. All studies reported last-observation-carried-forward (LOCF) as imputation method. We requested baseline-observation-carried-forward (BOCF) imputed analyses and any unpublished data from the manufacturer but the manufacturers denied the request. Two out of the four oxycodone-controlled studies and one out of the three placebo-controlled studies did not provided data on responder's rate. Two studies were considered to be of high risk of bias.In comparison to placebo, tapentadol was associated with a mean reduction of 0.56 points (95% confidence interval (CI) 0.92 to 0.20) in the 11-point numerical rating scale (NRS) at 12 weeks and with a 1.36 increase (95% CI 1.13 to 1.64) in the risk of responding to treatment (number needed to treat for an additional beneficial outcome (NNTB) 16; 95% CI 9 to 57, for 12-weeks). Moderate-to-high heterogeneity was found for the efficacy outcome estimates. Tapentadol was associated with a 2.7 fold increase (95% CI 2.05 to 3.52) in the risk of discontinuing treatment due to adverse effects number needed to treat for an additional harmful outcome (NNTH) 10; 95%CI 7 to 12, for 12 weeks).In comparison to oxycodone, pooled data showed a 0.24 points (95%CI 0.43 to 0.05) reduction in pain intensity from baseline in the 11-point NRS. The two studies that evaluated responder's rate showed a non-significant 1.46 increase (95% CI 0.92 to 2.32) in the risk of responding to treatment among tapentadol treated patients. Tapentadol was associated with a 50% risk reduction (95% CI 42% to 60%) of discontinuing treatment due to adverse effects (NNTB 6; 95% CI 5 to 7, for 12 weeks). Tapentadol was also associated with a 9% reduction (95% CI 4 to 15) in the overall risk of adverse effects (NNTH 18; 95% CI 12 to 35, for 12 weeks) and with a non-significant 43% reduction (95% CI 33 to 76) in the risk of serious adverse effects. Moderate to high heterogeneity was found for most efficacy (except for the primary outcome) and safety outcome estimates. Subgroup analysis showed a higher improvement with tapentadol among patients with knee osteoarthritis and among pooled results from studies of higher quality and shorter follow-up period, although there were no statistical significant differences in the effect size between these subgroups.
AUTHORS' CONCLUSIONS
Tapentadol extended release is associated with a reduction in pain intensity in comparison to placebo and oxycodone. However, the clinical significance of the results is uncertain due to the following reasons: modest difference between interventions in efficacy outcomes, high heterogeneity in some comparisons and outcomes, high withdrawals rates, lack of data for the primary outcome in some studies and impossibility to use BOCF as imputation method. Tapentadol is associated with a more favourable safety profile and tolerability than oxycodone.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Clinical Trials, Phase III as Topic; Humans; Low Back Pain; Musculoskeletal Pain; Osteoarthritis, Knee; Oxycodone; Phenols; Randomized Controlled Trials as Topic; Tapentadol
PubMed: 26017279
DOI: 10.1002/14651858.CD009923.pub2 -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
The Cochrane Database of Systematic... Mar 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong opioids used for cancer pain relief. However, strong opioids are ineffective as pain treatment in all patients and are not well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with superior, inferior or equal pain relief and tolerability compared to other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of buprenorphine for pain in adults and children with cancer.
SEARCH METHODS
We searched CENTRAL (the Cochrane Library) issue 12 or 12 2014, MEDLINE (via OVID) 1948 to 20 January 2015, EMBASE (via OVID) 1980 to 20 January 2015, ISI Web of Science (SCI-EXPANDED & CPCI-S) to 20 January 2015, ISI BIOSIS 1969 to 20 January 2015. We also searched ClinicalTrials.gov (http://clinicaltrials.gov/; metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/) and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain (IASP; via European Journal of Pain Supplements) on 16 February 2015. We checked the bibliographic references of identified studies as well as relevant studies and systematic reviews to find additional trials not identified by the electronic searches. We contacted authors of included studies for other relevant studies.
SELECTION CRITERIA
We included randomised controlled trials, with parallel-group or crossover design, comparing buprenorphine (any formulation and any route of administration) with placebo or an active drug (including buprenorphine) for cancer background pain in adults and children.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data pertaining to study design, participant details (including age, cancer characteristics, previous analgesic medication and setting), interventions (including details about titration) and outcomes, and independently assessed the quality of the included studies according to standard Cochrane methodology. As it was not feasible to meta-analyse the data, we summarised the results narratively. We assessed the overall quality of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons.Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability.Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study).Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study).In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine.The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship.The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality.
AUTHORS' CONCLUSIONS
Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.
Topics: Administration, Cutaneous; Administration, Oral; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Child; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 25826743
DOI: 10.1002/14651858.CD009596.pub4 -
The Cochrane Database of Systematic... Mar 2015Oral analgesia is a convenient and widely used form of pain relief following caesarean section. It includes various medications used at different doses alone or in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral analgesia is a convenient and widely used form of pain relief following caesarean section. It includes various medications used at different doses alone or in adjunction to other form of analgesia.
OBJECTIVES
To determine the effectiveness, safety and cost-effectiveness of oral analgesia for post-caesarean pain relief.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs). Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over trials were not eligible for inclusion.Interventions included oral medication given to women for post-caesarean pain relief compared with oral medication, or placebo/no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed for inclusion all the potential studies and independently assessed trial quality, extracted the data using the agreed data extraction form, and checked them for accuracy.
MAIN RESULTS
Eight small trials involving 962 women (out of 13 included trials) contributed data to the analysis, of which only four trials had low risk of bias.None of the included studies reported on 'adequate pain relief', which is one of this review's primary outcomes. 1. Opiod analgesics versus placeboBased on one trial involving 120 women, the effect of opioids versus placebo was not significant in relation to the need for additional pain relief (primary outcome) (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.06 to 1.92), and the effect in terms of adverse drug effects outcomes was also uncertain (RR 6.58, 95% CI 0.38 to 113.96).Low (75 mg) and high (150 mg) doses of tramadol had a similar effect on the need for additional pain relief (RR 0.67, 95% CI 0.12 to 3.78 and RR 0.14, 95% CI 0.01 to 2.68, respectively, one study, 80 women). 2. Non-opioid analgesia versus placeboThe confidence interval for the lower requirement for additional analgesia (primary outcome) with the non-opioid analgesia group was wide and includes little or no effect (average RR 0.70, 95% CI 0.48 to 1.01, six studies, 584 women). However, we observed substantial heterogeneity due to the variety of non-opioid drugs used (I(2) = 85%). In a subgroup analysis of different drugs, only gabapentin use resulted in less need for additional pain relief (RR 0.34, 95% CI 0.23 to 0.51, one trial, 126 women). There was no difference in need for additional pain relief with the use of celexocib, ibuprofen, ketoprofen, naproxen, paracetamol. Maternal drug effects were more common with the use of non-opioid analgesics (RR 11.12, 95% CI 2.13 to 58.22, two trials, 267 women).Gabapentin 300 mg (RR 0.25, 95% CI 0.13 to 0.49, one study, 63 women) and 600 mg (RR 0.44, 95% CI 0.27 to 0.71, one study, 63 women) as well as ketoprofen 100 mg (RR 0.55, 95% CI 0.39 to 0.79, one study 72 women) were both more effective than placebo with respect to the need for additional pain relief. However, the 50 mg ketoprofen group and the placebo group did not differ in terms of the number of women requiring additional pain relief (RR 0.82, 95% CI 0.64 to 1.07, one study, 72 women). 3. Combination analgesics versus placeboOur pooled analysis for the effect of combination analgesics on the need for additional pain relief was RR 0.70 (95% CI 0.35 to 1.40, three trials, 242 women, I(2) = 69%). When comparing different drugs within the combination oral analgesics versus placebo comparison we observed subgroup differences (P = 0.05; I² = 65.8%). One trial comparing paracetamol plus codeine versus placebo resulted in fewer women requiring additional pain relief (RR 0.44, 95% CI 0.23 to 0.82, one trial, 65 women). However, there were no differences in the the number of women requiring additional pain relief when comparing paracetamol plus oxycodone versus placebo, or paracetamol plus propoxyphene (RR 1.00, 95% CI 0.78 to 1.28, one trial, 96 women and RR 0.65, 95% CI 0.11 to 3.69, one trial, 81 women, respectively).Maternal drug effects were more common in combination analgesics group versus placebo (RR 13.18, 95% CI 2.86 to 60.68, three trials, 252 women). 4. Opioid analgesics versus non-opioid analgesicsThe confidence interval for the effect on additional pain relief between opioid and non-opioid drugs was very wide (RR 0.51, 95% CI 0.07 to 3.51, one trial, 121 women). Side effects were more common with the use opioids versus non-opioids analgesics (RR 2.32, 95% CI 1.15 to 4.69, two trials 241 women). 5. Opioid analgesics versus combination analgesicsThere was no difference in need for additional pain relief in opioid analgesics versus combination analgesics based on one study involving 121 women comparing tramadol and paracetamol plus propoxyphene (RR 0.51, 95% CI 0.07 to 3.51). Maternal adverse effects also did not differ between the two groups (RR 6.74, 95% CI 0.39 to 116.79). 6. Non-opioid versus combination analgesicsThe need for additional pain relief was greater in the group of women who received non-opoid analgesics (RR 0.87, 95% CI 0.81 to 0.93, one trial, 192 women) compared with the group of women who received combination analgesics. Secondary outcomes not reported in the included studiesNo data were found on the following secondary outcomes: number of days in hospital post-operatively, re-hospitalisation due to incisional pain, fully breastfeeding on discharge, mixed feeding at discharge, incisional pain at six weeks after caesarean section, maternal post partum depression, effect (negative) on mother and baby interaction and cost of treatment.
AUTHORS' CONCLUSIONS
Eight trials with 962 women were included in the analysis, but only four trials were of high quality. All the trials were small. We carried out subgroup analysis for different drugs within the same group and for high versus low doses of the same drug. However, the relatively few studies (one to two trials) and numbers of women (40 to 136) limits the reliability of these subgroup analyses.Due to limited data available no conclusions can be made regarding the safest and the most effective form of oral analgesia for post-caesarean pain. Further studies are necessary.
Topics: Administration, Oral; Adult; Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Cesarean Section; Drug Therapy, Combination; Female; Humans; Pain, Postoperative; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 25821010
DOI: 10.1002/14651858.CD010450.pub2 -
The Cochrane Database of Systematic... Feb 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search.
SELECTION CRITERIA
We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach.
MAIN RESULTS
We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events.Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings.The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety.
AUTHORS' CONCLUSIONS
Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Administration Schedule; Humans; Morphine; Neoplasms; Oxycodone; Pain; Pain Management; Randomized Controlled Trials as Topic
PubMed: 25723351
DOI: 10.1002/14651858.CD003870.pub5