-
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 -
The Cochrane Database of Systematic... Jul 2016This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two conditions. This review considers neuropathic pain only.Opioid drugs, including oxycodone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration. Separate reviews consider other opioids.
OBJECTIVES
To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 6 November 2013 for the original review and from January 2013 to 21 December 2015 for this update. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. This update differs from the earlier review in that we have included studies using oxycodone in combination with naloxone, and oxycodone used as add-on treatment to stable, but inadequate, treatment with another class of drug.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing any dose or formulation of oxycodone with placebo or another active treatment in chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.
MAIN RESULTS
The updated searches identified one additional published study, and one clinical trial registry report. We included five studies reporting on 687 participants; 637 had painful diabetic neuropathy and 50 had postherpetic neuralgia. Two studies used a cross-over design and three used a parallel group design; all studies used a placebo comparator, although one study used an active placebo (benztropine). Modified-release oxycodone (oxycodone MR) was titrated to effect and tolerability. One study used a fixed dose combination of oxycodone MR and naloxone. Two studies added oxycodone therapy to ongoing, stable treatment with either pregabalin or gabapentin. All studies had one or more sources of potential major bias.No study reported the proportion of participants experiencing 'substantial benefit' (at least 50% pain relief or who were very much improved). Three studies (537 participants) in painful diabetic neuropathy reported outcomes equivalent to 'moderate benefit' (at least 30% pain relief or who were much or very much improved), which was experienced by 44% of participants with oxycodone and 27% with placebo (number needed to treat for one additional beneficial outcome (NNT) 5.7).All studies reported group mean pain scores at the end of treatment. Three studies reported a greater pain intensity reduction and better patient satisfaction with oxycodone MR alone than with placebo. There was a similar result in the study adding oxycodone MR to stable, ongoing gabapentin, but adding oxycodone MR plus naloxone to stable, ongoing pregabalin did not show any additional effect.More participants experienced adverse events with oxycodone MR alone (86%) than with placebo (63%); the number needed to treat for an additional harmful outcome (NNH) was 4.3. Serious adverse events (oxycodone 3.4%, placebo 7.0%) and adverse event withdrawals (oxycodone 11%, placebo 6.4%) were not significantly different between groups. Withdrawals due to lack of efficacy were less frequent with oxycodone MR (1.1%) than placebo (11%), with a number needed to treat to prevent one withdrawal of 10. The add-on studies reported similar results.We downgraded the quality of the evidence to very low for all outcomes, due to limitations in the study methods, heterogeneity in the pain condition and study methods, and sparse data.
AUTHORS' CONCLUSIONS
There was only very low quality evidence that oxycodone (as oxycodone MR) is of value in the treatment of painful diabetic neuropathy or postherpetic neuralgia. There was no evidence for other neuropathic pain conditions. Adverse events typical of opioids appeared to be common.
Topics: Adult; Aged; Analgesics, Opioid; Constipation; Delayed-Action Preparations; Diabetic Neuropathies; Disorders of Excessive Somnolence; Dizziness; Female; Humans; Male; Middle Aged; Nausea; Neuralgia, Postherpetic; Oxycodone; Randomized Controlled Trials as Topic
PubMed: 27465317
DOI: 10.1002/14651858.CD010692.pub3 -
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 -
Journal of Pain and Symptom Management Nov 2017Opioid-induced constipation (OIC) is one of the most frequent and severe adverse events (AEs) after treatment with opioids. Recent studies have indicated that... (Comparative Study)
Comparative Study Meta-Analysis Review
Opioid-Induced Constipation Relief From Fixed-Ratio Combination Prolonged-Release Oxycodone/Naloxone Compared With Oxycodone and Morphine for Chronic Nonmalignant Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
CONTEXT
Opioid-induced constipation (OIC) is one of the most frequent and severe adverse events (AEs) after treatment with opioids. Recent studies have indicated that fixed-ratio combination prolonged-release oxycodone/naloxone (OXN PR) could decrease OIC with similar pain relief compared with other opioids.
OBJECTIVES
We systematically reviewed (PROSPERO registration numbers: CRD42016036244) the constipation relief of OXN PR compared with other opioids regardless of formulation, prolonged release, or extended release used for the relief of chronic pain.
METHODS
Relevant studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane library from inception to May 2016, with an update to December 2016. We quantitatively analyzed OIC (assessed by bowel function index [BFI]), pain intensity, and AEs.
RESULTS
A total of 167 articles were identified from the databases. Finally seven studies with 3217 patients were included in our meta-analysis, including 1322 patients in OXN PR treatment groups and 1885 patients in prolonged-release oxycodone (OXY PR) or prolonged-release morphine (MOR PR) control group. The relative risk (RR) of OIC was decreased in OXN PR (RR 0.52, 95% CI 0.44; 0.62). Whether BFI was better or worse at baseline, the mean difference (MD) of BFI -17.48 95% CI -21.60; -13.36) was better after treatment with OXN PR with clinical importance at the end of intervention; moreover, the BFI of the OXN PR-treated group was closer to normal BFI scores. However, clinical BFI change from baseline to the end measurement only existed in patients when the baseline BFI was high (mean [SDs] 61.0 [23.39]-67.40 [19.51]), and the MD of the BFI was -15.96 (95% CI -25.56; -15.48). The RR of AEs was also smaller (RR 0.80; 95% CI 0.69-0.93), but the severity or duration of AEs was not reported. Pain intensity was also significantly decreased in the OXN PR treatment groups (MD -3.84, 95% CI -7.14; -0.55), although there was no clinically meaningful difference.
CONCLUSION
For people with chronic pain, treatment with OXN PR decreases the incidence of OIC and provides intermediate-term bowel function improvement with clinical importance; in addition, pain relief is not weakened. The OIC after treatment with OXN PR for cancer-related pain and over the long term remains unknown.
Topics: Analgesics, Opioid; Chronic Pain; Constipation; Delayed-Action Preparations; Drug Combinations; Drug Therapy, Combination; Humans; Morphine; Naloxone; Oxycodone; Randomized Controlled Trials as Topic
PubMed: 28736104
DOI: 10.1016/j.jpainsymman.2017.07.025 -
Medicine Apr 2016The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang... (Meta-Analysis)
Meta-Analysis Review
The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69-1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72-1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70-1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38-1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81-1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58-1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44-1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07-1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25-0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Humans; Neoplasms; Oxycodone; Pain; Randomized Controlled Trials as Topic
PubMed: 27082588
DOI: 10.1097/MD.0000000000003341 -
JAMA Internal Medicine Nov 2016Overuse of medical care is an increasingly recognized problem in clinical medicine. (Review)
Review
IMPORTANCE
Overuse of medical care is an increasingly recognized problem in clinical medicine.
OBJECTIVE
To identify and highlight original research articles published in 2015 that are most likely to reduce overuse of medical care, organized into 3 categories: overuse of testing, overtreatment, and questionable use of services. The articles were reviewed and interpreted for their importance to clinical medicine.
EVIDENCE REVIEW
A structured review of English-language articles on PubMed published in 2015 and review of tables of contents of relevant journals to identify potential articles that related to medical overuse in adults.
FINDINGS
Between January 1, 2015, and December 31, 2015, we reviewed 1445 articles, of which 821 addressed overuse of medical care. Of these, 112 were deemed most relevant based on their originality, methodologic quality, and number of patients potentially affected. The 10 most influential articles were selected by consensus using the same criteria. Findings included a doubling of specialty referrals and advanced imaging for simple headache (from 6.7% in 2000 to 13.9% in 2010); unnecessary hospital admission for low-risk syncope, often leading to adverse events; and overly frequent colonoscopy screening for 34% of patients. Overtreatment was common in the following areas: 1 in 4 patients with atrial fibrillation at low risk for thromboembolism received anticoagulation; 94% of testosterone replacement therapy was administered off guideline recommendations; 91% of patients resumed taking opioids after overdose; and 61% of patients with diabetes were treated to potentially harmfully low hemoglobin A1c levels (<7%). Findings also identified medical practices to question, including questionable use of treatment of acute low-back pain with cyclobenzaprine and oxycodone/acetaminophen; of testing for Clostridium difficile with molecular assays; and serial follow-up of benign thyroid nodules.
CONCLUSIONS AND RELEVANCE
The number of articles on overuse of medical care nearly doubled from 2014 to 2015. The present review promotes reflection on the top 10 articles and may lead to questioning other non-evidence-based practices.
Topics: Delivery of Health Care; Evidence-Based Medicine; Guidelines as Topic; Health Services Misuse; Humans; Mass Screening; Medical Overuse; Patient Readmission; Prescription Drug Overuse; Quality of Health Care; Randomized Controlled Trials as Topic; United States; Unnecessary Procedures
PubMed: 27654002
DOI: 10.1001/jamainternmed.2016.5381 -
Cureus Sep 2023Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the... (Review)
Review
Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects.
PubMed: 37727840
DOI: 10.7759/cureus.45485 -
Pain Physician May 2016Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from... (Review)
Review
BACKGROUND
Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from prescription opioid analgesics constitutes a large portion of total overdose events. The societal burden associated with these events is a frequently overlooked public health concern.
OBJECTIVES
To evaluate unintentional, non-fatal prescription opioid overdoses, including the identification of risk factors, societal burden, and knowledge gaps where further study is warranted.
STUDY DESIGN
Systematic review of the literature for unintentional, non-fatal opioid overdose.
METHODS
Preferred reporting items for systematic reviews and meta-analyses guidelines were used in constructing this systematic review. To determine the scope of the existing literature, a systematic search was conducted using the MEDLINE, CINAHL, PsycINFO, and Web of Science databases.
RESULTS
This systematic review analyzes 24 articles (21 retrospective descriptive analyses, 2 prospective analyses, one phase III trial, and one meta-analysis). Articles were reviewed by authors and relevant data examined. Results show that opioid overdose morbidity is significantly more prevalent than mortality and sequelae of non-fatal events should be studied in more detail.
LIMITATIONS
The limitations of this systematic review include the range of study populations and opioids discussed and the broad and variable definitions of "opioid overdose" in the literature.
CONCLUSIONS
Opioid overdose morbidity and mortality is seen across the entire spectrum of inpatient and outpatient use with significant numbers of adverse events occurring in population segments not identified by high risk indicators. Increased physician awareness and a multi-modal approach could help mitigate the overdose epidemic while maintaining effective pain control for patients.
KEY WORDS
Prescription, opioid, accidental drug overdose, unintentional overdose, drug poisoning, fentanyl, oxycodone, hydrocodone, methadone, oxymorphone, hydromorphone.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Prescription Drug Overuse
PubMed: 27228510
DOI: No ID Found -
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 -
The Cochrane Database of Systematic... Mar 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong opioids used for cancer pain relief. However, strong opioids are ineffective as pain treatment in all patients and are not well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with superior, inferior or equal pain relief and tolerability compared to other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of buprenorphine for pain in adults and children with cancer.
SEARCH METHODS
We searched CENTRAL (the Cochrane Library) issue 12 or 12 2014, MEDLINE (via OVID) 1948 to 20 January 2015, EMBASE (via OVID) 1980 to 20 January 2015, ISI Web of Science (SCI-EXPANDED & CPCI-S) to 20 January 2015, ISI BIOSIS 1969 to 20 January 2015. We also searched ClinicalTrials.gov (http://clinicaltrials.gov/; metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/) and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain (IASP; via European Journal of Pain Supplements) on 16 February 2015. We checked the bibliographic references of identified studies as well as relevant studies and systematic reviews to find additional trials not identified by the electronic searches. We contacted authors of included studies for other relevant studies.
SELECTION CRITERIA
We included randomised controlled trials, with parallel-group or crossover design, comparing buprenorphine (any formulation and any route of administration) with placebo or an active drug (including buprenorphine) for cancer background pain in adults and children.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data pertaining to study design, participant details (including age, cancer characteristics, previous analgesic medication and setting), interventions (including details about titration) and outcomes, and independently assessed the quality of the included studies according to standard Cochrane methodology. As it was not feasible to meta-analyse the data, we summarised the results narratively. We assessed the overall quality of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons.Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability.Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study).Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study).In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine.The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship.The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality.
AUTHORS' CONCLUSIONS
Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.
Topics: Administration, Cutaneous; Administration, Oral; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Child; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 25826743
DOI: 10.1002/14651858.CD009596.pub4