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Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.

ABSTRACT: 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.

SUBMITTER: Furlan AD

PROVIDER: S-EPMC1459894 | biostudies-other | 2006 May

REPOSITORIES: biostudies-other

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Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.

Furlan Andrea D AD Sandoval Juan A JA Mailis-Gagnon Angela A Tunks Eldon E

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20060501 11

<h4>Background</h4>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.<h4>Methods</h4>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, E ...[more]

PMID: 16717269

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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: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:BackgroundOpioids 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.MethodsWe 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.ResultsUsing 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.ConclusionThis 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 registrationThis 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.

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:UnlabelledOpioids are regularly administered in acute and cancer pain. In chronic non-cancer pain (CNCP), however, their use is controversial. Previous meta-analyses and randomized controlled trials (RCTs) lack methodological homogeneity and comparable data. Here we analysed the maximum analgesic efficacies of opioids and non-opioids compared with placebo, and of physiotherapy and psychotherapy compared with active or waiting-list controls. We screened 3647 citations and included RCTs if treatment duration was at least 3 weeks, data were sufficient for meta-analysis, and criteria for high quality were met. Only 46 studies (10 742 patients) met the criteria. Weighted and standardized mean differences (WMD, SMD) between pain intensities were pooled to conduct separate meta-analyses for each treatment category. At the end of treatment the WMD for pain reduction (100-point scale) was 12.0 for 'strong' opioids, 10.6 for 'weak' opioids, 8.4 for non-opioids (each vs. placebo), 5.5 for psychotherapy and 4.5 for physiotherapy (each vs. active controls). Dropout rates were high in pharmacological studies. The 95% confidence intervals using the outcomes of control groups did not indicate statistical differences between efficacies of the five interventions. Because not enough eligible head-to-head trials were available, our analysis is limited to adjusted indirect comparisons. The heterogeneity of pre-post pain differences in control groups did not allow the definition of a common comparator. In conclusion, although there were statistically significant differences between maximum treatment efficacies, no intervention per se produced clinically important improvements in average pain intensity. Thus, opioids alone are inappropriate and multimodal treatment programmes may be required for CNCP.Linked articlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Project description:Objectives: To determine the prevalence and factors associated with the use of opioids among patients with chronic non-cancer pain (CNCP). Methods: A systematic review and meta-analysis. Comprehensive literature searches in Medline-PubMed, Embase and SCOPUS databases. Original studies published between 2009 and 2019 with a cross-sectional design were included. The quality of the studies was assessed with Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute. Protocol registered in the International Prospective Register of Systematic Reviews with reference number: CRD42019137990. Results: Out of the 1,310 potential studies found, 25 studies fulfilled the inclusion criteria. Most of the studies were of high quality. High levels of heterogeneity were found in the studies included. In the general population, the prevalence of long-term opioid use was 2.3% (95% CI: 1.5-3.6%), the prevalence of short-term opioid use was 8.1% (95% CI: 5.6-11.6%), and among people with chronic low back pain it was 5.8% (95% CI: 0.5-45.5%). The prevalence of opioid use among patients from the health records or medical surveys was 41% (95% CI: 23.3-61.3%). Finally, in patients with musculoskeletal pain, the prevalence was 20.5% (95% CI: 12.9-30.9%) and in patients with fibromyalgia, 24.5% (95% CI: 22.9-26.2%). A higher prevalence of opioid use was observed among men, younger people, patients receiving prescriptions of different types of drugs, smokers and patients without insurance or with noncommercial insurance. In addition, non-white and Asian patients were less likely to receive opioids than non-Hispanic white patients. Conclusions: The prevalence of opioid use among patients with CNCP was higher in subjects with short or occasional use compared to those with long-term use. Men, younger people, more chronic pain conditions, and patients without insurance or with noncommercial insurance were most related to opioid use. However, non-white and Asian patients, and those treated by a physician trained in complementary medicine were less likely to use opioids.

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Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.

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Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.

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