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BMJ (Clinical Research Ed.) Oct 2021To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip...
OBJECTIVE
To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES
The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS
Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS
192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS
Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO number CRD42020213656.
Topics: Acetaminophen; Administration, Oral; Administration, Topical; Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Network Meta-Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Management
PubMed: 34642179
DOI: 10.1136/bmj.n2321 -
Journal of Opioid Management 2022To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables.
DESIGN
Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA).
SETTING
A systematic review.
DATA SOURCES
A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019.
ELIGIBILITY CRITERIA
RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items.
RESULTS
52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10].
CONCLUSIONS
The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.
Topics: Humans; Analgesia, Patient-Controlled; Analgesics, Opioid; Network Meta-Analysis; Tramadol; Morphine
PubMed: 36523208
DOI: 10.5055/jom.2022.0751 -
Experimental Biology and Medicine... Nov 2023The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the...
The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.
Topics: Analgesics, Opioid; Bayes Theorem; Data Mining; Fentanyl; Hydrocodone; Hydromorphone; Meperidine; Oxycodone; Oxymorphone; Tapentadol; United States
PubMed: 38158803
DOI: 10.1177/15353702231211860 -
Pain Physician Jan 2021Chronic low back pain (CLBP) incurs huge costs owing to increased healthcare expenditure, disability, insurance, and work absenteeism. Opioid analgesics are commonly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic low back pain (CLBP) incurs huge costs owing to increased healthcare expenditure, disability, insurance, and work absenteeism. Opioid analgesics are commonly used for the management of CLBP.
OBJECTIVE
To compare and rank the opioids used in the management of CLBP, in terms of efficacy and safety.
STUDY DESIGN
Systematic review and network meta-analyses (NMA).
METHOD
The search was conducted in Embase, PubMed, Cochrane databases for randomized controlled trials (RCTs) that had evaluated the efficacy and safety of opioids in CLBP. Two authors independently performed data extraction and quality assessment. The proportion of patients reporting either 30% or 50% reduction in pain from baseline to follow-up on the numeric rating scale, was measured as efficacy outcome. Pairwise meta-analyses and Bayesian NMA, within the random-effects model, were used to synthesize data. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I 2 and deviation information criteria.
RESULTS
Twenty-three RCTs with a total of 8,420 patients, evaluating 13 different opioids were included in this NMA. For 30% pain reduction, oxymorphone (OR: 5.36; 95% CrI: 1.02-30.3), tramadol with acetaminophen (OR: 2.37; 95% CrI: 1.08-5.17), and buprenorphine (OR: 2.29; 95% CrI: 1.05-5.07) shown statistically significant more effective than placebo. For 50% pain reduction, the statistically significant difference is observed with buprenorphine (OR: 2.38 95% CrI: 1.08-5.24), oxymorphone (OR: 5.10; 95% CrI: 1.31-20.41), and tramadol with acetaminophen (OR: 2.11; 95% CrI: 1.07-4.21). Hydrocodone (OR: 0.33; 95% CrI: 0.14-0.77) was found statistically safer compared to the other opioids.
LIMITATIONS
Only 5 trials had more than a 12-week study duration. We need clinical trials with longer follow-up as CLBP management requires a longer duration, and long-term prescribing of opioids associated with severe adverse event profile, development of tolerance, and dependence.
CONCLUSIONS
Oxymorphone has an advantage over other opioids to reduce pain by 30% and 50% in patients with CLBP.
Topics: Analgesics, Opioid; Bayes Theorem; Chronic Pain; Humans; Low Back Pain; Network Meta-Analysis
PubMed: 33400430
DOI: No ID Found -
Expert Review of Clinical Pharmacology May 2021: Chronic low back pain (LBP) is common, and some patients require opiates therapy. This Bayesian network meta-analysis (NMA) analyzed available randomized clinical... (Meta-Analysis)
Meta-Analysis
: Chronic low back pain (LBP) is common, and some patients require opiates therapy. This Bayesian network meta-analysis (NMA) analyzed available randomized clinical trials (RCTs) on the use of opioids for LBP.: All RCTs comparing two or more opioids for chronic LBP and reporting results under the Numeric Rating Scale were included. The following drugs were analyzed: fentanyl, morphine, tapentadol, oxycodone, buprenorphine, oxymorphone, tramadol. The NMA was performed through the STATA routine for Bayesian hierarchical random-effects model analysis, with standardized mean difference (SMD) effect measure. Data regarding the rate of adverse events and different drug formulations were also reported.: Data from 2933 patients were obtained, with a mean age of 53.30 ± 6.95 years. The mean duration of symptoms prior to beginning the trial was 95.16 ± 47.29 months. The mean follow-up was 3.29 ± 1.72 months. Among the analyzed compounds, oxymorphone, tapentadol and fentanyl showed the highest efficacy in terms of pain reduction.: According to published level I evidence, oxymorphone, tapentadol and fentanyl were the most effective drugs in the treatment of chronic LBP. However, different formulation and pharmacokinetic characteristics need to be taken into consideration when choosing the ideal compound for a given patient.
Topics: Analgesics, Opioid; Bayes Theorem; Chronic Pain; Humans; Low Back Pain; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33706636
DOI: 10.1080/17512433.2021.1903316 -
Anesthesia and Analgesia Oct 2019Side effects of opioids used for the treatment of acute pain frequently limit their analgesic quality. Many studies have compared opioid side effects in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Side effects of opioids used for the treatment of acute pain frequently limit their analgesic quality. Many studies have compared opioid side effects in patient-controlled analgesia (PCA), but it remains unclear whether there are specific side effect profiles that can be exploited when choosing an opioid for a patient. In this review, we wanted to determine the risk ratios (RRs) for the most common side effects when using different opioids for intravenous PCA in equianalgesic doses and rank the substances accordingly.
METHODS
A search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified 63 randomized controlled trials comparing opioids under equianalgesic conditions. Inclusion criteria were comparable pain stimulus between groups, equal coanalgesic treatment, and comparable resulting pain scores. Quality of studies was assessed using the Cochrane risk of bias tool with 6 items. Frequentistic network meta-analysis was conducted with morphine as the comparator. This method not only summarizes all estimated effects from direct comparisons of different interventions but also allows for indirect comparisons between interventions that can be linked via the common comparator, in which case the indirect evidence can be used to enhance the precision of the direct comparisons. Primary end points of this study were RRs for nausea and vomiting, pruritus, and events of sedation, as well as mean differences for scores of sedation. Events of respiratory depression were counted. Secondary end point was patient satisfaction (mean difference). The study protocol was registered at PROSPERO (CRD42017062355).
RESULTS
Sixteen opioid interventions were compared in the largest network (nausea and vomiting outcome) and 7 opioid interventions in the smallest network (sedation events outcome). Most interventions did not differ from morphine on the primary outcomes (side effects), with some exceptions. Buprenorphine had a significantly higher RR of nausea and vomiting, whereas fentanyl had a lower RR of nausea and vomiting. Nalbuphine, butorphanol, methadone, and pethidine/meperidine had a lower risk of pruritus. Respiratory depression was rare (22 of 2452 patients). Pethidine/meperidine, fentanyl, and oxymorphone caused significantly lower sedation scores. Tramadol caused significantly lower satisfaction scores, whereas oxycodone, alfentanil, remifentanil, fentanyl, and pethidine/meperidine caused significantly higher satisfaction scores.
CONCLUSIONS
The opiate chosen for treatment most likely has little effect on the incidence of pruritus and nausea/vomiting, although considerable differences exist in terms of better and worse opioids in the presented rankings. Larger differences between drugs were observed with regard to sedation and patient satisfaction, and choosing the appropriate opioid may help to improve PCA in this regard.
Topics: Acute Pain; Administration, Intravenous; Analgesia, Patient-Controlled; Analgesics, Opioid; Consciousness; Dose-Response Relationship, Drug; Humans; Network Meta-Analysis; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 30418234
DOI: 10.1213/ANE.0000000000003887 -
Current Drug Metabolism 2020Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent... (Meta-Analysis)
Meta-Analysis
Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans.
BACKGROUND
Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA).
METHODS
To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach.
RESULTS
The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses.
CONCLUSION
This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.
Topics: Analgesics, Opioid; Humans; Models, Biological; Osteoarthritis; Oxycodone; Oxymorphone; Pain; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 32407270
DOI: 10.2174/1389200221666200514130441