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Current Medical Research and Opinion Jul 2011To conduct a systematic review of evidence supporting the efficacy and safety profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) introduced in the last decade for... (Review)
Review
OBJECTIVE
To conduct a systematic review of evidence supporting the efficacy and safety profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) introduced in the last decade for the treatment of patients with osteoarthritis (OA), including their analgesic effects, ability to improve function, and adverse event profiles relative to current standards of care.
RESEARCH DESIGN AND METHODS
Systematic search of the literature for NSAIDs approved by the FDA (2000-2010).
RESULTS
One new orally-administered NSAID molecule (meloxicam), two orally-administered NSAID formulations (naproxen plus lansoprazole; oxycodone/ibuprofen), and three topical NSAID formulations (diclofenac patch, gel, and solution) were approved by the FDA (2000-2010). A systematic literature review found evidence to support efficacy in treating patients with OA for all agents except oxycodone/ibuprofen, which has not been studied in this patient population, although ibuprofen and immediate-release oxycodone have been studied individually for OA pain. Evidence quality was inconsistent, with several agents lacking long-term, controlled trials against active comparators, and functional end points inconsistently met. Although low-dose meloxicam and naproxen plus lansoprazole offer a reduced risk of adverse gastrointestinal (GI) events, cardiovascular and renal risks remain similar to traditional oral NSAID therapy. Further, only lower doses of meloxicam appear to carry a reduced risk of GI events. Diclofenac patch, gel, and solution preparations offer the potential for reduced GI, cardiovascular, and renal adverse events. The level of evidence available to support the efficacy and safety of these agents for long-term treatment of patients with OA differs, with some having only short-term trials, while others have longer-duration trials with active comparators.
CONCLUSIONS
By expanding the treatment armamentarium, newly-approved NSAID agents may improve the ability of clinicians to tailor analgesic therapy for their diverse patient populations and to achieve realistic functional improvements. The comparisons in this article were limited to drugs that received approval after 2000 and should be considered accordingly.
Topics: Administration, Oral; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis; Standard of Care; Transdermal Patch
PubMed: 21561395
DOI: 10.1185/03007995.2011.568058 -
The Cochrane Database of Systematic... Aug 2017Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, 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), and PsycINFO (Ovid) to November 2016. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
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 by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall quality of the evidence using GRADE.
MAIN RESULTS
For this update, we identified six new studies (1258 participants) for inclusion. In total, we included 23 studies which enrolled/randomised 2648 participants, with 2144 of these analysed for efficacy and 2363 for safety. The studies examined a number of different drug comparisons.Pooled analysis of three of the four studies comparing controlled-release (CR) oxycodone to immediate-release (IR) oxycodone showed that the ability of CR and IR oxycodone to provide pain relief were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). Pooled analyses of adverse events showed no significant differences between CR and IR oxycodone for asthenia (risk ratio (RR) 0.58, 95% CI 0.2 to 1.68), confusion (RR 0.78, 95% CI 0.2 to 3.02), constipation (RR 0.71, 95% CI 0.45 to 1.13), dizziness/lightheadedness (RR 0.74, 95% CI 0.4 to 1.37), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), dry mouth (RR 1.14, 95% CI 0.48 to 2.75), insomnia (RR 1.04, 95% CI 0.31 to 3.53), nausea (RR 0.85, 95% CI 0.56 to 1.28), nervousness (RR 0.57, 95% CI 0.2 to 1.64), pruritus (RR 1.46, 95% CI 0.65 to 3.25), vomiting (RR 0.66, 95% CI 0.38 to 1.15), and discontinuation due to adverse events (RR 0.6, 95% CI 0.29 to 1.22). The quality of the evidence was very low for all these adverse events. Three of the four studies found similar results for treatment acceptability.Pooled analysis of seven of the nine studies comparing CR oxycodone to CR morphine indicated that pain relief was significantly better after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; low quality evidence). However, sensitivity analysis did not corroborate this result (SMD 0.12, 95% CI -0.02 to 0.26).Pooled analyses of adverse events showed no significant differences between CR oxycodone and CR morphine for confusion (RR 1.01 95% CI 0.78 to 1.31), constipation (RR 0.98, 95% CI 0.82 to 1.16), dizziness/lightheadedness (RR 0.76, 95% CI 0.33 to 1.76), drowsiness/somnolence (RR 0.9, 95% CI 0.75 to 1.08), dry mouth (RR 1.01, 95% CI 0.8 to 1.26), dysuria (RR 0.71, 95% CI 0.4 to 1.26), nausea (RR 1.02, 95% CI 0.82 to 1.26), pruritus (RR 0.81, 95% CI 0.51 to 1.29), vomiting (RR 0.94, 95% CI 0.68 to 1.29), and discontinuation due to adverse events (RR 1.06, 95% CI 0.43 to 2.6). However, the RR for hallucinations was significantly lower after treatment with CR oxycodone compared to CR morphine (RR 0.52, 95% CI 0.28 to 0.97). The quality of the evidence was very low for all these adverse events. There were no marked differences in treatment acceptability or quality of life ratings.The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None 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 high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review. The data suggest that oxycodone offers similar levels of pain relief and overall adverse events to other strong opioids including morphine. Although we identified a clinically insignificant benefit on pain relief in favour of CR morphine over CR oxycodone, this did not persist following sensitivity analysis and so we do not consider this important. However, in this updated analysis, we found that hallucinations occurred less often with CR oxycodone than with CR morphine, but the quality of this evidence was very low so this finding should be treated with utmost caution. Our conclusions are consistent with other 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 are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Aged; Analgesics, Opioid; Cancer Pain; Constipation; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphine; Nausea; Neoplasms; Oxycodone; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Sleep Stages; Vomiting
PubMed: 28829910
DOI: 10.1002/14651858.CD003870.pub6 -
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 -
The Cochrane Database of Systematic... Sep 2016This review replaces part of an earlier review that evaluated oxycodone for both neuropathic pain and fibromyalgia, which has now been split into separate reviews for... (Review)
Review
BACKGROUND
This review replaces part of an earlier review that evaluated oxycodone for both neuropathic pain and fibromyalgia, which has now been split into separate reviews for the two conditions. This review will consider pain in fibromyalgia only.Opioid drugs are commonly used to treat fibromyalgia, but they may not be beneficial for people with this condition. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration.
OBJECTIVES
To assess the analgesic efficacy and adverse events of oxycodone for treating pain in fibromyalgia in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE for randomised controlled trials from inception to 25 July 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA
We planned to include randomised, double-blind trials of eight weeks' duration or longer, comparing oxycodone (alone or in fixed-dose combination with naloxone) with placebo or another active treatment. We did not include observational studies.
DATA COLLECTION AND ANALYSIS
The plan was for two independent review authors to extract data and assess trial quality and potential bias. Where pooled analysis was possible, we planned to use dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.
MAIN RESULTS
No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and are very uncertain about estimates of benefit and harm.
AUTHORS' CONCLUSIONS
There is no randomised trial evidence to support or refute the suggestion that oxycodone, alone or in combination with naloxone, reduces pain in fibromyalgia.
PubMed: 27582266
DOI: 10.1002/14651858.CD012329 -
Drugs & Aging Aug 2012Mild cognitive deficits are experienced by 18% of community-dwelling older adults, many of whom do not progress to dementia. The effect of commonly used medication on... (Review)
Review
BACKGROUND
Mild cognitive deficits are experienced by 18% of community-dwelling older adults, many of whom do not progress to dementia. The effect of commonly used medication on subtle impairments in cognitive function may be under-recognized.
OBJECTIVE
The aim of the review was to examine the evidence attributing amnestic or non-amnestic cognitive impairment to the use of medication with anticholinergic, antihistamine, GABAergic or opioid effects.
METHODS
MEDLINE and EMBASE were searched for randomized, double-blind, placebo-controlled trials of adults without underlying central nervous system disorders who underwent detailed neuropsychological testing prior to and after oral administration of drugs affecting cholinergic, histaminergic, GABAergic or opioid receptor pathways. Seventy-eight studies were identified, reporting 162 trials testing medication from the four targeted drug classes. Two investigators independently appraised study quality and extracted relevant data on the occurrence of amnestic, non-amnestic or combined cognitive deficits induced by each drug class. Only trials using validated neuropsychological tests were included. Quality of the evidence for each drug class was assessed based on consistency of results across trials and the presence of a dose-response gradient.
RESULTS
In studies of short-, intermediate- and long-acting benzodiazepine drugs (n = 68 trials), these drugs consistently induced both amnestic and non-amnestic cognitive impairments, with evidence of a dose-response relationship. H(1)-antihistamine agents (n = 12) and tricyclic antidepressants (n = 15) induced non-amnestic deficits in attention and information processing. Non-benzodiazepine derivatives (n = 29) also produced combined deficits, but less consistently than benzodiazepine drugs. The evidence was inconclusive for the type of cognitive impairment induced by different bladder relaxant antimuscarinics (n = 9) as well as for narcotic agents (n = 5) and antipsychotics (n = 5). Among healthy volunteers >60 years of age, low doses of commonly used medications such as lorazepam 0.5 mg, oxybutynin immediate release 5 mg and oxycodone 10 mg produced combined deficits.
CONCLUSION
Non-amnestic mild cognitive deficits are consistently induced by first-generation antihistamines and tricyclic antidepressants, while benzodiazepines provoke combined amnestic and non-amnestic impairments. Risk-benefit considerations should be discussed with patients in order to enable an informed choice about drug discontinuation or substitution to potentially reverse cognitive adverse effects.
Topics: Amnesia; Analgesics, Opioid; Cholinergic Antagonists; Cognitive Dysfunction; GABA Agents; Histamine Antagonists; Humans
PubMed: 22812538
DOI: 10.1007/BF03262280 -
The Clinical Journal of Pain May 2020Tapentadol (TAP) immediate release (IR) is a newer opioid option for acute pain. The aim of this systematic review was to examine the efficacy and safety of TAP IR... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tapentadol (TAP) immediate release (IR) is a newer opioid option for acute pain. The aim of this systematic review was to examine the efficacy and safety of TAP IR compared with other opioids for acute pain.
METHODS
A systematic literature search as conducted using the Cochrane Library, Embase, International Pharmaceutical Abstracts, MEDLINE, PubMed, and Web of Science. The search included all randomized controlled trials and observational studies examining TAP IR versus other orally administered IR opioids for acute pain. The protocol for this study was registered on PROSPERO (CRD42018110267).
RESULTS
Thirteen studies and 1 abstract were included in the systematic review (n=12,814 patients). Of these, 5 studies and 1 abstract were included in the qualitative review (n=9108 patients). Eight randomized controlled trials (n=3706 patients) comparing 50 to 100 mg TAP IR versus 5 to 15 mg oxycodone IR were included in the meta-analysis. The lowest dose of TAP IR (ie, 50 mg) was associated with less pain control compared with oxycodone IR (standardized mean difference=0.25, 95% confidence interval: 0.06-0.44, P<0.01). However, there were no significant differences at higher doses (ie, 75, 100 mg, or when a titration strategy was used). In the qualitative analysis, pain control with TAP IR was also similar to morphine IR and tramadol IR. TAP IR was less likely to have gastrointestinal adverse effects such as nausea and constipation compared with other opioids.
DISCUSSION
TAP IR is as effective as other opioids at higher doses for acute pain and is associated with fewer gastrointestinal adverse effects. On the basis of these findings, TAP IR can be considered as a first-line opioid for acute pain.
Topics: Acute Pain; Analgesics, Opioid; Humans; Observational Studies as Topic; Oxycodone; Randomized Controlled Trials as Topic; Tapentadol
PubMed: 31990693
DOI: 10.1097/AJP.0000000000000809 -
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 -
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 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 -
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