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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 -
Pain Physician Jul 2012The non-medical use of and harms related to prescription opioid (PO) analgesics - key medications to treat severe and chronic pain - are an emerging public health... (Review)
Review
BACKGROUND
The non-medical use of and harms related to prescription opioid (PO) analgesics - key medications to treat severe and chronic pain - are an emerging public health concern globally. PO use is proportionally highest in North America, where, consequently, nonmedical PO use (NMPOU) and morbidity/mortality are high and well documented for the United States. Canada is the country with the second highest PO consumption rate in the world - with steeper recent increases in PO use than the US - mainly driven by substantial increases in the use of strong opioids (e.g., oxycodone). Indications and select data of NMPOU and PO-related morbidity and mortality have emerged in recent years, yet a systematic and comprehensive collection of relevant data to characterize the phenomenon in Canada does not exist.
OBJECTIVES
This paper comprehensively reviews the available data in Canada regarding NMPOU, and PO-related harms, diversion, and interventions, and discusses implications for interventions and policy.
STUDY DESIGN
Narrative literature/data review.
SETTING
Canada.
METHODS
Publicly available data and information - either from journal publications, "grey literature" (e.g., government/technical reports) or Web sites reporting relevant data on Canada - were searched and narratively reviewed.
RESULTS
Indicators on NMPOU and PO-related harms in Canada are highly fragmented, and not nearly as systematic and comprehensive as they are in the US; virtually no national statistics/data are collected. Available -largely provincial/local - data indicate that PO misuse is increasingly common in key populations, including general adult and student populations, street-drug users, First Nations/Aboriginal Peoples, and correctional populations. Co-morbidities - e.g., pain, mental health problems, polysubstance use - among people reporting NMPOU appear to be high. Substance use treatment admissions for those with problematic PO use have risen substantially where reported. Opioid-related mortality (and oxycodone-related mortality, specifically) have increased considerably in Ontario where relevant data from the mid-1990s onward have been examined. In Canadian populations reporting NMPOU, sourcing of POs occurs through various diversion routes, including from family/friends, "double-doctoring," or street drug markets. In addition, losses and theft/robberies from pharmacies and licensed medications dealers appear to be on the rise. Finally, interventions (i.e., provincial PO guidelines, prescription monitoring programs, substance use treatment services) are fragmented and inconsistently applied throughout the country, and currently fail to effectively address the growing problem of NMPOU and PO-related harms across Canada.
LIMITATIONS
This review did not rely on systematic review methodologies.
CONCLUSION
Corresponding to its increasing and high overall PO consumption levels, NMPOU and PO-related harms in Canada are high based on available data, and likely now constitute the third highest level of substance use burden of disease (after alcohol and tobacco). The data and monitoring situation in Canada regarding NMPOU and PO-related harms are fragmented, un-systematic, and insufficient. While major and concerted policy initiatives - primarily from the federal level - are absent to date, these urgently require vastly improved national data indicators and monitoring in order to allow for and evaluate evidence-based interventions on this urgent and extensive public health problem.
Topics: Analgesics, Opioid; Canada; Chronic Pain; Humans; Opioid-Related Disorders
PubMed: 22786457
DOI: No ID Found -
Pain Research and Treatment 2012Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only...
Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects.
PubMed: 22619711
DOI: 10.1155/2012/154781 -
The Cochrane Database of Systematic... Sep 2011Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data.
OBJECTIVES
To summarise data from all Cochrane Reviews that have assessed the effects 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 taken alone.
METHODS
We identified 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 numbers 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 (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, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event.
MAIN RESULTS
The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (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. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions.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 in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids.Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg.Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours.
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. 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: Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative; Review Literature as Topic; Tooth Extraction
PubMed: 21901726
DOI: 10.1002/14651858.CD008659.pub2 -
Neurology May 2011To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). (Review)
Review
Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.
OBJECTIVE
To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN).
METHODS
We performed a systematic review of the literature from 1960 to August 2008 and classified the studies according to the American Academy of Neurology classification of evidence scheme for a therapeutic article, and recommendations were linked to the strength of the evidence. The basic question asked was: "What is the efficacy of a given treatment (pharmacologic: anticonvulsants, antidepressants, opioids, others; and nonpharmacologic: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?"
RESULTS AND RECOMMENDATIONS
Pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness, and few studies have sufficient information on treatment effects on function and QOL.
Topics: Analgesics, Opioid; Anticonvulsants; Antidepressive Agents; Diabetic Neuropathies; Electric Stimulation Therapy; Electromagnetic Fields; Evidence-Based Medicine; Humans; Pain; Pain Management
PubMed: 21482920
DOI: 10.1212/WNL.0b013e3182166ebe -
Journal of Pain and Symptom Management Feb 2010Opioids are recommended for control of moderate-to-severe, chronic, malignant, and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone has... (Meta-Analysis)
Meta-Analysis Review
Opioids are recommended for control of moderate-to-severe, chronic, malignant, and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone has recently been launched. The aim of this review was to assess the effectiveness of oxymorphone as an analgesic in chronic pain. A systematic search for published studies of oral oxymorphone in the management of chronic pain was conducted. The studies were evaluated for their internal validity according to standard criteria. They were also evaluated for their external validity and research ethic aspects. A meta-analysis was performed to examine the effect of oxymorphone compared with placebo. Nine studies were evaluated; three were excluded because of low quality. Six controlled studies (duration 2-12 weeks) included a total of 1489 subjects suffering from chronic low back pain, chronic pain from osteoarthritis, and chronic cancer pain. Three of the studies were of high quality and three of medium quality. External validity was assessed to be high, medium, and low (in one, three, and two studies, respectively). The meta-analysis suggests that daily doses of 40-100mg are superior to placebo; however, the estimate (reduction of pain intensity compared with placebo) of the treatment effect is imprecise (95% confidence interval -17.08, -8.69). Limited evidence suggests that oxymorphone is effective for pain control in patients with cancer. No significant differences between oxymorphone and oxycodone at equipotent doses were found. In conclusion, oxymorphone is superior to placebo. There is no evidence that the efficacy of oxymorphone differs from other opioids.
Topics: Analgesics, Opioid; Chronic Disease; Humans; Low Back Pain; Neoplasms; Osteoarthritis; Oxymorphone; Pain; Randomized Controlled Trials as Topic
PubMed: 20152592
DOI: 10.1016/j.jpainsymman.2009.07.010 -
The Cochrane Database of Systematic... Oct 2009Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Opioids may be a viable treatment option if... (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 the elderly. Opioids may be a viable treatment option if patients suffer from severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory.
OBJECTIVES
To determine the effects on pain and function and the safety of oral or transdermal opioids as compared with placebo or no intervention in patients with osteoarthritis of the hip or knee.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE, EMBASE, and CINAHL (up to 28 July 2008), checked conference proceedings, reference lists, and contacted authors.
SELECTION CRITERIA
Studies were included if they were randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in patients with osteoarthritis of the knee or hip. Studies of tramadol were excluded. No language restrictions were applied.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate. Standardised mean differences (SMDs) and 95% confidence intervals (CI) were calculated for pain and function, and risk ratios for safety outcomes. Trials were combined using inverse-variance random-effects meta-analysis.
MAIN RESULTS
Ten trials with 2268 participants were included. Oral codeine was studied in three trials, transdermal fentanyl and oral morphine in one trial each, oral oxycodone in four, and oral oxymorphone in two trials. Overall, opioids were more effective than control interventions in terms of pain relief (SMD -0.36, 95% CI -0.47 to -0.26) and improvement of function (SMD -0.33, 95% CI -0.45 to -0.21). We did not find substantial differences in effects according to type of opioid, analgesic potency (strong or weak), daily dose, duration of treatment or follow up, methodological quality of trials, and type of funding. Adverse events were more frequent in patients receiving opioids compared to control. The pooled risk ratio was 1.55 (95% CI 1.41 to 1.70) for any adverse event (4 trials), 4.05 (95% CI 3.06 to 5.38) for dropouts due to adverse events (10 trials), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials). Withdrawal symptoms were more severe after fentanyl treatment compared to placebo (SMD 0.60, 95% CI 0.42 to 0.79; 1 trial).
AUTHORS' CONCLUSIONS
The small to moderate beneficial effects of non-tramadol opioids are outweighed by large increases in the risk of adverse events. Non-tramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe.
Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 19821302
DOI: 10.1002/14651858.CD003115.pub3 -
Polskie Archiwum Medycyny Wewnetrznej 2009Safe and effective chronic opioid therapy (COT) for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and in the... (Review)
Review
2009 Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: what are the key messages for clinical practice?
Safe and effective chronic opioid therapy (COT) for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and in the assessment and management of risks associated with opioid abuse, addiction, and diversion. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on COT for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations based on the best available evidence. This article summarizes key clinical messages from this guideline regarding patient selection and risk stratification, informed consent and opioid management plans, initiation and titration of COT, use of methadone, monitoring of patients, use of opioids in high-risk patients, assessment of aberrant drug-related behaviors, dose escalations and high-dose opioid therapy, opioid rotation, indications for discontinuation of therapy, prevention and management of opioid-related adverse effects, driving and work safety, identifying a medical home and when to obtain consultation, and management of breakthrough pain.
Topics: Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; Drug Monitoring; Evidence-Based Medicine; Humans; Methadone; Morphine; Opioid-Related Disorders; Oxycodone; Pain; Pain Measurement; Practice Guidelines as Topic
PubMed: 19776687
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2009Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm.
OBJECTIVES
To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults.
SEARCH STRATEGY
Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009.
SELECTION CRITERIA
Randomised, double blind, placebo-controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time-to-use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected.
MAIN RESULTS
This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal.
AUTHORS' CONCLUSIONS
Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non-steroidal anti-inflammatory drugs, with the benefit of longer duration of action.
Topics: Acetaminophen; Acute Disease; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Drug Synergism; Drug Therapy, Combination; Humans; Oxycodone; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 19588335
DOI: 10.1002/14651858.CD002763.pub2 -
BMJ Clinical Evidence Jul 2008Up to 80% of people with cancer experience pain at some time during their illness, and most will need opioid analgesics. This review assesses how different opioid... (Review)
Review
INTRODUCTION
Up to 80% of people with cancer experience pain at some time during their illness, and most will need opioid analgesics. This review assesses how different opioid analgesics compare, in terms of both pain control and adverse effects, in people with cancer.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: what are the effects of opioids in treating cancer-related pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: codeine, dihydrocodeine, transdermal fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol.
Topics: Administration, Oral; Analgesics; Analgesics, Opioid; Codeine; Fentanyl; Humans; Methadone; Neoplasms; Oxycodone; Pain
PubMed: 19445735
DOI: No ID Found