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Clinical Therapeutics Jan 2015The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management... (Review)
Review
PURPOSE
The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients' daily functioning.
METHODS
Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments.
FINDINGS
Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, -5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies.
IMPLICATIONS
Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.
Topics: Chronic Pain; Constipation; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Headache; Humans; Naloxone; Nausea; Oxycodone; Phenols; Quality of Life; Tapentadol; Vomiting
PubMed: 25592091
DOI: 10.1016/j.clinthera.2014.12.001 -
The Cochrane Database of Systematic... Sep 2014Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009.
OBJECTIVES
To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an update performed on 15 August 2012), checked conference proceedings, reference lists, and contacted authors.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied no language restrictions.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain and function, and risk ratios for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis.
MAIN RESULTS
We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms).
AUTHORS' CONCLUSIONS
The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.
Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 25229835
DOI: 10.1002/14651858.CD003115.pub4 -
American Journal of Public Health Aug 2014We review evidence of determinants contributing to increased opioid-related mortality in the United States and Canada between 1990 and 2013. We identified 17... (Review)
Review
We review evidence of determinants contributing to increased opioid-related mortality in the United States and Canada between 1990 and 2013. We identified 17 determinants of opioid-related mortality and mortality increases that we classified into 3 categories: prescriber behavior, user behavior and characteristics, and environmental and systemic determinants. These determinants operate independently but interact in complex ways that vary according to geography and population, making generalization from single studies inadvisable. Researchers in this area face significant methodological difficulties; most of the studies in our review were ecological or observational and lacked control groups or adjustment for confounding factors; thus, causal inferences are difficult. Preventing additional opioid-related mortality will likely require interventions that address multiple determinants and are tailored to specific locations and populations.
Topics: Analgesics, Opioid; Canada; Humans; Methadone; Noscapine; Opioid-Related Disorders; Oxycodone; Practice Patterns, Physicians'; Risk Factors; Socioeconomic Factors; United States
PubMed: 24922138
DOI: 10.2105/AJPH.2014.301966 -
Continuum (Minneapolis, Minn.) Jun 2014Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older... (Review)
Review
PURPOSE OF REVIEW
Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older have diabetes mellitus, 95% of whom have type 2. This article reviews the effects of diabetes mellitus on the neuromuscular system.
RECENT FINDINGS
Diabetes mellitus leads to diverse forms of peripheral neuropathy as the major neuromuscular complication. Both focal and diffuse types of neuropathy can develop, with the most common form being diabetic sensorimotor polyneuropathy. Small fibers are damaged early in the development of diabetic sensorimotor polyneuropathy and are not assessed by nerve conduction studies. Small fiber damage occurs even in the prediabetes stage. No disease-modifying therapy for diabetic sensorimotor polyneuropathy is available at this time, but this complication can be limited in patients who have type 1 diabetes mellitus with strict glycemic control; the same outcome is not clearly observed in patients who have type 2 diabetes mellitus. Recently, the evidence base for symptomatic treatments of painful diabetic sensorimotor polyneuropathy underwent systematic review. Effective evidence-based treatments include some anticonvulsants (eg, pregabalin, gabapentin), antidepressants (eg, amitriptyline, duloxetine), opioids (eg, morphine sulfate, oxycodone), capsaicin cream, and transcutaneous electrical nerve stimulation.
SUMMARY
This article reviews the increasing prevalence of diabetes mellitus and diabetic sensorimotor polyneuropathy and discusses recent consensus opinion on the objective confirmation needed for the diagnosis in the clinical research setting. The evidence from clinical trials shows that intensive glycemic control reduces prevalence of diabetic sensorimotor polyneuropathy in patients with type 1 diabetes mellitus, but variable outcomes are observed in patients with type 2 diabetes mellitus. Finally, despite the lack of disease-modifying treatment, effective evidence-based therapy can control painful symptoms of diabetic sensorimotor polyneuropathy.
Topics: Aged; Diabetic Neuropathies; Humans; Male; Middle Aged
PubMed: 24893232
DOI: 10.1212/01.CON.0000450964.30710.a0 -
The Cochrane Database of Systematic... May 2014There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient.
OBJECTIVES
To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain.
SEARCH METHODS
We assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl, oxycodone, and codeine.
SELECTION CRITERIA
We included randomised studies using multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine) in cancer pain. These were taken from four existing or ongoing Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted adverse event data, and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness, appetite, and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium, dizziness, hallucinations, mood change and somnolence relating to patient consciousness, and nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia, asthenia, dehydration, or dry mouth relating to appetite or thirst.Comparative measures of harm were known to be unlikely, and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid, and for all four opioid drugs combined.
MAIN RESULTS
We included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used.Direct measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below.
AUTHORS' CONCLUSIONS
We found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine.We are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.
Topics: Analgesics, Opioid; Appetite; Codeine; Consciousness; Fentanyl; Humans; Middle Aged; Morphine; Neoplasms; Oxycodone; Pain; Randomized Controlled Trials as Topic; Terminal Care; Thirst
PubMed: 24874470
DOI: 10.1002/14651858.CD011056.pub2 -
BMC Musculoskeletal Disorders Mar 2014This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis.
METHODS
A systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ≥12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions.WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors.
RESULTS
Thirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%.Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics.
CONCLUSIONS
This analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses.
Topics: Acetaminophen; Administration, Oral; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Drug Evaluation; Duloxetine Hydrochloride; Etoricoxib; Humans; Narcotics; Osteoarthritis; Pain Measurement; Pyridines; Sulfones; Thiophenes; Treatment Outcome
PubMed: 24618328
DOI: 10.1186/1471-2474-15-76 -
The Cochrane Database of Systematic... Aug 2013The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these medications remain unclear. This review is an update of a Cochrane review first published in 2007.
OBJECTIVES
To determine the efficacy of opioids in adults with CLBP.
SEARCH METHODS
We electronically searched the Cochrane Back Review Group's Specialized Register, CENTRAL, CINAHL and PsycINFO, MEDLINE, and EMBASE from January 2006 to October 2012. We checked the reference lists of these trials and other relevant systematic reviews for potential trials for inclusion.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that assessed the use of opioids (as monotherapy or in combination with other therapies) in adults with CLBP that were at least four weeks in duration. We included trials that compared non-injectable opioids to placebo or other treatments. We excluded trials that compared different opioids only.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the risk of bias and extracted data onto a pre-designed form. We pooled results using Review Manager (RevMan) 5.2. We reported on pain and function outcomes using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (95% CI). We used absolute risk difference (RD) with 95% CI to report adverse effects.
MAIN RESULTS
We included 15 trials (5540 participants). Tramadol was examined in five trials (1378 participants); it was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44; low quality evidence) and function (SMD -0.18, 95% CI -0.29 to -0.07; moderate quality evidence). Transdermal buprenorphine (two trials, 653 participants) may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25; very low quality evidence), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25; very low quality evidence). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), examined in six trials (1887 participants), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33; moderate quality evidence) and function (SMD -0.26, 95% CI -0.37 to -0.15; moderate quality evidence). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function (SMD -0.11, 95% -0.63 to 0.42; very low quality evidence). The included trials in this review had high drop-out rates, were of short duration, and had limited interpretability of functional improvement. They did not report any serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism). In general, the effect sizes were medium for pain and small for function.
AUTHORS' CONCLUSIONS
There is some evidence (very low to moderate quality) for short-term efficacy (for both pain and function) of opioids to treat CLBP compared to placebo. The very few trials that compared opioids to non-steroidal anti-inflammatory drugs (NSAIDs) or antidepressants did not show any differences regarding pain and function. The initiation of a trial of opioids for long-term management should be done with extreme caution, especially after a comprehensive assessment of potential risks. There are no placebo-RCTs supporting the effectiveness and safety of long-term opioid therapy for treatment of CLBP.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Female; Humans; Low Back Pain; Male; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 23983011
DOI: 10.1002/14651858.CD004959.pub4 -
The Cochrane Database of Systematic... Jun 2013Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Fixed-dose combinations of ibuprofen and oxycodone are available, and the drugs may be separately used in combination in some acute pain situations.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus oxycodone for moderate to severe postoperative pain.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, (CENTRAL), on The Cochrane Library, (Issue 4 of 12, 2013), MEDLINE (1950 to 21st May 2013), EMBASE (1974 to 21st May 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles.
SELECTION CRITERIA
Randomised, double-blind clinical trials of single dose, oral ibuprofen plus oxycodone compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus oxycodone, ibuprofen alone, oxycodone alone, or placebo with at least 50% pain relief over six hours, using validated equations. We calculated relative risk (RR) and number needed to treat to benefit (NNT). We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events.
MAIN RESULTS
Searches identified three studies involving 1202 participants. All examined the same dose combination. Included studies provided data from 603 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with placebo, 717 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with ibuprofen 400 mg alone, and 471 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with oxycodone 5 mg alone.The proportion of participants achieving at least 50% pain relief over 6 hours was 60% with ibuprofen 400 mg + oxycodone 5 mg and 17% with placebo, giving an NNT of 2.3 (2.0 to 2.8). For ibuprofen 400 mg alone the proportion was 50%, producing no significant difference between ibuprofen 400 mg + oxycodone 5 mg and ibuprofen 400 mg alone. For oxycodone 5 mg alone the proportion was 23%, giving an NNT for ibuprofen 400 mg + oxycodone 5 mg compared with oxycodone alone of 2.9 (2.3 to 4.0).Ibuprofen + oxycodone resulted in longer times to remedication than with placebo. The median time to use of rescue medication was more than 5 hours for ibuprofen 400 mg + oxycodone 5 mg, and 2.3 hours or less with placebo. Fewer participants needed rescue medication with ibuprofen + oxycodone combination than with placebo or ibuprofen alone. The proportion was 40% with ibuprofen 400 mg + oxycodone 5 mg, 83% with placebo, 53% with ibuprofen alone, and 83% with oxycodone alone, giving NNT to prevent one patient needing rescue medication of 2.4 (2.0 to 2.9), 11 (6.1 to 56), and 2.6 (2.1 to 3.4) for comparisons of ibuprofen 400 mg + oxycodone 5 mg with placebo, ibuprofen alone, and oxycodone alone, respectively.The proportion of participants experiencing one or more adverse events was 25% with ibuprofen 400 mg + oxycodone 5 mg, 25% with placebo, 26% with ibuprofen alone, and 35% with oxycodone alone; they were not significantly different. Serious adverse events were reported only after abdominal surgery 6/169 with the combination, 1/175 with ibuprofen alone, 3/52 with oxycodone alone, and 1/60 with placebo. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms.
AUTHORS' CONCLUSIONS
The combination of ibuprofen 400mg + oxycodone 5mg provided analgesia for longer than oxycodone alone, but not ibuprofen alone (at the same dose). There was also a smaller chance of needing additional analgesia over about eight hours, and with no greater chance of experiencing an adverse event.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Drug Combinations; Humans; Ibuprofen; Oxycodone; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 23801549
DOI: 10.1002/14651858.CD010289.pub2 -
The Cochrane Database of Systematic... Nov 2012Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe pain due to life-threatening... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe pain due to life-threatening illnesses; however, their use in chronic non-cancer pain (CNCP) is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile.
OBJECTIVES
To assess the analgesic effectiveness and safety of methadone in the treatment of CNCP.
SEARCH METHODS
We identified both randomized controlled trials (RCTs) and non-randomized studies of methadone use in chronic pain by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2011, issue 11, MEDLINE (1950 to November 2011), and EMBASE (1980 to November 2011), together with reference lists of retrieved papers and reviews.
SELECTION CRITERIA
We included RCTs with pain assessment as either the primary or secondary outcome. Quasi-randomized studies, cohorts and case-control trials were also considered for inclusion because we suspected that the beneficial and harmful effects of methadone in CNCP may not be adequately addressed in RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted efficacy and adverse event data and assessed risk of bias.
MAIN RESULTS
We included two RCTs and one non-randomized study, involving a total of 181 participants. Both RCTs were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other involving 76 participants with postherpetic neuralgia. Study phases were 20 days and approximately eight weeks, respectively. The non-randomized study retrospectively evaluated 86 outpatients over an average of 8.8 ± 6.3 months.One RCT reported average pain intensity and pain relief, and found statistically significant improvements versus placebo for both outcomes, with 10 mg and 20 mg daily doses of methadone. The second RCT reported differences in pain reduction between methadone and morphine and found morphine to be statistically superior. The non-randomized study found that in patients initially prescribed methadone it was effective in fewer participants than in those initially prescribed other long-acting opioids (28% versus 42%, 33% and 50% for morphine, oxycodone and transdermal fentanyl, respectively).One RCT compared incidences for several individual adverse events, but found a difference between methadone and placebo for only one event, dizziness (P = 0.041).
AUTHORS' CONCLUSIONS
The three studies provide very limited evidence of the efficacy of methadone for CNCP, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Methadone; Neuralgia; Neuralgia, Postherpetic; Randomized Controlled Trials as Topic
PubMed: 23152251
DOI: 10.1002/14651858.CD008025.pub2 -
Pain Physician Jul 2012In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician's armamentarium. Though opioids are... (Review)
Review
BACKGROUND
In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician's armamentarium. Though opioids are used regularly for cancer pain, there is a paucity of literature proving efficacy for long-term use. Cancer is no longer considered a "terminal disease"; 50% to 65% of patients survive for at least 2 years, and there are about 12 million cancer survivors in the United States. There is a concern about side effects, tolerance, abuse and addiction with long-term opioid use and a need to evaluate the effectiveness of opioids for cancer pain.
OBJECTIVE
The objective of this systematic review was to look at the effectiveness of opioids for cancer pain.
STUDY DESIGN
A systematic review of randomized trials of opioids for cancer pain.
METHODS
A comprehensive review of the current literature for randomized controlled trials (RCTs) of opioids for cancer pain was done. The literature search was done using PubMed, EMBASE, Cochrane library, clinical trials, national clearing house, Web of Science, previous narrative systematic reviews, and cross references. The studies were assessed using the modified Cochrane and Jadad criteria. Analysis of evidence was done utilizing the modified quality of evidence developed by United States Preventive Services Task Force (USPSTF).
OUTCOME MEASURES
Pain relief was the primary outcome measure. Secondary outcome measures are quality of life (QoL) and side effects including tolerance and addiction.
RESULTS
The level of evidence for pain relief based on the USPSTF criteria was fair for transdermal fentanyl and poor for morphine, tramadol, oxycodone, methadone, and codeine.
LIMITATIONS
Randomized trials in a cancer setting are difficult to perform and justify. There is a paucity of long-term trials and this review included a follow-up period of only 4 weeks.
CONCLUSION
This systematic review of RCTs of opioids for cancer pain showed fair evidence for the efficacy of transdermal fentanyl and poor evidence for morphine, tramadol, oxycodone, methadone, and codeine.
Topics: Analgesics, Opioid; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 22786461
DOI: No ID Found