Dataset Information

Individual opioids, and long- versus short-acting opioids, for chronic noncancer pain: Protocol for a network meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.

Methods

We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ??4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting.

Results

Using a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo.

Conclusion

This NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations.

Systematic review registration

This systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=110331.

SUBMITTER: Noori A

PROVIDER: S-EPMC6824796 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Individual opioids, and long- versus short-acting opioids, for chronic noncancer pain: Protocol for a network meta-analysis of randomized controlled trials.

Noori Atefeh A Busse Jason W JW Sadeghirad Behnam B Siemieniuk Reed A RA Wang Li L Couban Rachel R Juurlink David N DN Thabane Lehana L Guyatt Gordon H GH

Medicine 20191001 43

<h4>Background</h4>Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.<h4>Methods</h4>We will conduct a network meta-analysis (NMA) of randomized co ...[more]

PMID: 31651885

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Project description:ImportanceLong-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes.ObjectiveTo compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain.Design, setting, and participantsRetrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care.ExposuresPropensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications).Main outcomes and measuresTotal and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication.ResultsThere were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean [SD] age, 48 [11] years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years.Conclusions and relevancePrescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.

Project description:BackgroundOpioid use for chronic non-cancer pain (CNCP) is complex. In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC).MethodsThe clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed. Two categories of guidance are given: Evidence-based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case-series, case-control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) and formal multistep procedures to reach a set of consensus recommendations. The clinical practice recommendations were reviewed by five external reviewers from North America and Europe and were also posted for public comment.ResultsThe key clinical practice recommendations suggest: (a) first optimizing established non-pharmacological treatments and non-opioid analgesics and (b) considering opioid treatment if established non-pharmacological treatments or non-opioid analgesics are not effective and/or not tolerated and/or contraindicated. Evidence- and clinical consensus-based potential indications and contraindications for opioid treatment are presented. Eighteen GCP recommendations give guidance regarding clinical evaluation, as well as opioid treatment assessment, monitoring, continuation and discontinuation.ConclusionsOpioids remain a treatment option for some selected patients with CNCP under careful surveillance.SignificanceIn chronic pain, opioids are neither a universal cure nor a universally dangerous weapon. They should only be used for some selected chronic noncancer pain syndromes if established non-pharmacological and pharmacological treatment options have failed in supervised pain patients as part of a comprehensive, multi-modal, multi-disciplinary approach to treatment. In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients.

Project description:ImportanceHarms and benefits of opioids for chronic noncancer pain remain unclear.ObjectiveTo systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain.Data sources and study selectionThe databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control.Data extraction and synthesisPaired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence.Main outcomes and measuresThe primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting.ResultsNinety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points]).Conclusions and relevanceIn this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Project description:BACKGROUND: Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction. METHODS: This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7. RESULTS: Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant. INTERPRETATION: Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.

Project description:IntroductionOptimal pain management is crucial to the postoperative recovery process. We aimed to evaluate the efficacy and safety of intravenous oxycodone with intravenous fentanyl, morphine, sufentanil, pethidine, and hydromorphone for acute postoperative pain.MethodsA systematic literature search of PubMed, Cochrane Library, and EMBASE databases was performed for randomized controlled trials published from 2008 through 2017 (inclusive) that evaluated the acute postoperative analgesic efficacy of intravenous oxycodone against fentanyl, morphine, sufentanil, pethidine, and hydromorphone in adult patients (age ≥ 18 years). Outcomes examined included analgesic consumption, pain intensity levels, side effects, and patient satisfaction.ResultsEleven studies were included in the review; six compared oxycodone with fentanyl, two compared oxycodone with morphine, and three compared oxycodone with sufentanil. There were no eligible studies comparing oxycodone with pethidine or hydromorphone. Overall, analgesic consumption was lower with oxycodone than with fentanyl or sufentanil. Oxycodone exhibited better analgesic efficacy than fentanyl and sufentanil, and comparable analgesic efficacy to morphine. In terms of safety, there was a tendency towards more side effects with oxycodone than with fentanyl, but the incidence of side effects with oxycodone was comparable to morphine and sufentanil. Where patient satisfaction was evaluated, higher satisfaction levels were observed with oxycodone than with sufentanil and comparable satisfaction was noted when comparing oxycodone with fentanyl. Patient satisfaction was not evaluated in the studies comparing oxycodone with morphine.ConclusionsOur findings suggest that intravenous oxycodone provides better analgesic efficacy than fentanyl and sufentanil, and comparable efficacy to morphine with less adverse events such as sedation. No studies comparing intravenous oxycodone with pethidine or hydromorphone were identified in this review. Better alignment of study methodologies for future research in this area is recommended to provide the best evidence base for a meta-analysis.FundingMundipharma Singapore Holding Pte Ltd, Singapore.

Project description:BackgroundInternationally, there is concern about the increased prescribing of pharmaceutical opioids for chronic non-cancer pain (CNCP). In part, this is related to limited knowledge about the long-term benefits and outcomes of opioid use for CNCP. There has also been increased injection of some pharmaceutical opioids by people who inject drugs, and for some patients, the development of problematic and/or dependent use. To date, much of the research on the use of pharmaceutical opioids among people with CNCP, have been clinical trials that have excluded patients with complex needs, and have been of limited duration (i.e. fewer than 12 weeks). The Pain and Opioids In Treatment (POINT) study is unique study that aims to: 1) examine patterns of opioid use in a cohort of patients prescribed opioids for CNCP; 2) examine demographic and clinical predictors of adverse events, including opioid abuse or dependence, medication diversion, other drug use, and overdose; and 3) identify factors predicting poor pain relief and other outcomes.Methods/designThe POINT cohort comprises around 1,500 people across Australia prescribed pharmaceutical opioids for CNCP. Participants will be followed-up at four time points over a two year period. POINT will collect information on demographics, physical and medication use history, pain, mental health, drug and alcohol use, non-adherence, medication diversion, sleep, and quality of life. Data linkage will provide information on medications and services from Medicare (Australia's national health care scheme). Data on those who receive opioid substitution therapy, and on mortality, will be linked.DiscussionThis study will rigorously examine prescription opioid use among CNCP patients, and examine its relationship to important health outcomes. The extent to which opioids for chronic pain is associated with pain reduction, quality of life, mental and physical health, aberrant medication behavior and substance use disorders will be extensively examined. Improved understanding of the longer-term outcomes of chronic opioid therapy will direct community-based interventions and health policy in Australia and internationally. The results of this study will assist clinicians to better identify those patients who are at risk of adverse outcomes and who therefore require alternative treatment strategies.

Dataset Information

Individual opioids, and long- versus short-acting opioids, for chronic noncancer pain: Protocol for a network meta-analysis of randomized controlled trials.

Background

Methods

Results

Conclusion

Systematic review registration

Publications

Individual opioids, and long- versus short-acting opioids, for chronic noncancer pain: Protocol for a network meta-analysis of randomized controlled trials.

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