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Journal of Pain and Symptom Management Jun 2024Strong opioids are the cornerstone in the treatment of cancer-related pain.
CONTEXT
Strong opioids are the cornerstone in the treatment of cancer-related pain.
OBJECTIVES
This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain.
METHODS
PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks.
RESULTS
Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and nonsignificant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP.
CONCLUSION
The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.
PubMed: 38838946
DOI: 10.1016/j.jpainsymman.2024.05.022 -
Journal of Opioid Management 2024To examine recent literature and determine common clinical risk factors between antecedent traumatic brain injury (TBI) and the following development of opioid misuse...
OBJECTIVE
To examine recent literature and determine common clinical risk factors between antecedent traumatic brain injury (TBI) and the following development of opioid misuse and provide a framework for clinical identification of at-risk subjects and evaluate potential treatment implications within this association.
DESIGN
A comprehensive systematic literature search of PubMed was conducted for articles between 2000 and December 2022. Studies were included if the human participant had any head trauma exposure and any chronic opioid use or dependence. After eligibility criteria were applied, 16 studies were assessed for thematic trends.
RESULTS
Opioid use disorder (OUD) risks are heightened in cohorts with head trauma exposed to opioids while in the hospital, specifically with tramadol and oxycodone. Chronic pain was the most common predictor of long-term OUD, and continuous somatic symptoms associated with the TBI can lead to long-term opioid usage. Individuals who present with coexisting psychiatric conditions pose significantly more risk associated with a higher risk of long-term opioid use.
CONCLUSION
Findings indicate that therapists and clinicians must consider a risk profile for persons with TBI and follow an integrated care approach to account for mental health, prior substance misuse, presenting somatic symptoms, and current medication regimen during evaluation.
Topics: Humans; Analgesics, Opioid; Medically Unexplained Symptoms; Opioid-Related Disorders; Chronic Pain; Craniocerebral Trauma
PubMed: 38533717
DOI: 10.5055/jom.0846 -
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 -
Scientific Reports Nov 2019Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and... (Meta-Analysis)
Meta-Analysis
Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.
Topics: Analgesics; Animals; Disease Models, Animal; Pain; Peripheral Nervous System Diseases
PubMed: 31772391
DOI: 10.1038/s41598-019-54152-8 -
Pain Physician Nov 2019Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in...
BACKGROUND
Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in 47,600 American fatalities in 2017. Evidence suggests that despite guidelines and professional body recommendations, acute prescribing remains highly variable. Educational interventions targeting prescribers have potential to optimize prescribing in-line with evidence-based best practice.
OBJECTIVES
To identify the objective impacts of education interventions on opioid prescribing in the acute care setting.
STUDY DESIGN
A systematic literature review.
SETTING
The electronic databases MEDLINE, Embase, and Cochrane for works published until December 31, 2018. Bibliographies of relevant studies and the gray literature were also searched.
METHODS
Databases were searched for interventional studies (clinical trials and pre- and poststudies). Studies describing an educational intervention delivered to clinicians and reporting at least one objective measure of opioid use in the acute care setting were included. Studies reporting only subjective outcomes and those focused on chronic pain or set in primary care were excluded. Two reviewers (RB, TB) extracted data and assessed the quality of included studies using the Downs and Black Tool.
RESULTS
Nine studies met inclusion criteria; all used pre- and postdesigns. Three studies described stand-alone education, and the others described multifaceted interventions. All 9 interventions significantly reduced at least one of the following: high-risk agent use including meperidine use by up to 71%; total or daily dosage of opioids at discharge, including median morphine milligram equivalence (MME) from 90 mg to 45 mg per patient; and quantity of medications such as oxycodone supplied to patients, halved in one study from 6,170 expected to 2,932 supplied tablets. No increase in pain complaints or prescription refill requests were reported in those studies assessing these outcomes. The longest study examined prescribing 15 months after education delivery, reporting sustained practice changes.
LIMITATIONS
Overall study quality was fair to poor. Significant heterogeneity in settings, patient groups, methodologies, and outcomes prevented pooled quantitative analysis. No studies examined all available opioid agents or formulations.
CONCLUSIONS
These findings support prescriber education as an effective strategy to reduce opioid use and optimize prescribing in acute settings. Further research, particularly high quality randomized studies, describing the impact of education on all available opioid formulations and total MME is required. Reviewing the existing literature has offered useful models that can be implemented to improve care with opioid prescribing in acute settings.
KEY WORDS
Opioids, education, physician education, prescriber education, opioid education, opioid prescribing, systematic review, prescriptions, prevention.
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Opioid-Related Disorders; Oxycodone; Pain; Practice Patterns, Physicians'; Primary Health Care
PubMed: 31775401
DOI: No ID Found -
Pain Medicine (Malden, Mass.) Feb 2021To review studies examining the proportion of people with chronic noncancer pain who report consuming opioids and characteristics associated with their use. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To review studies examining the proportion of people with chronic noncancer pain who report consuming opioids and characteristics associated with their use.
DESIGN
Systematic review.
METHODS
We searched databases from inception to February 8, 2020, and conducted citation tracking. We included observational studies reporting the proportion of adults with chronic noncancer pain who used opioid analgesics. Opioids were categorized as weak (e.g., codeine) or strong (e.g., oxycodone). Study risk of bias was assessed, and Grading of Recommendations Assessment, Development and Evaluations provided a summary of the overall quality. Results were pooled using a random-effects model. Meta-regression determined factors associated with opioid use.
RESULTS
Sixty studies (N=3,961,739) reported data on opioid use in people with chronic noncancer pain from 1990 to 2017. Of these 46, 77% had moderate risk of bias. Opioid use was reported by 26.8% (95% confidence interval [CI], 23.1-30.8; moderate-quality evidence) of people with chronic noncancer pain. The use of weak opioids (17.3%; 95% CI 11.9-24.4; moderate-quality evidence) was more common than the use of strong opioids (9.8%; 95% CI, 6.8-14.0; low-quality evidence). Meta-regression determined that opioid use was associated with geographic region (P=0.02; lower in Europe than North America), but not sampling year (P=0.77), setting (P=0.06), diagnosis (P=0.34), or disclosure of funding (P=0.77).
CONCLUSIONS
Our review summarized data from over 3.9 million people with chronic noncancer pain reporting their opioid use. Between 1990 and 2017, one-quarter of people with chronic noncancer pain reported taking opioids, and this proportion did not change over time.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Observational Studies as Topic; Opioid-Related Disorders; Oxycodone; Prevalence
PubMed: 33164087
DOI: 10.1093/pm/pnaa322 -
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 -
Frontiers in Neuroscience 2021Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis...
Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis (NMA) aimed to compare the efficacy and safety of different drugs. After literature searching and screening, 46 trials, including 10,674 participants are included in this NMA. The pooled results showed that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. Cabergoline decreases IRLS scores to the greatest extent among all drugs (MD -11.98, 95% CI -16.19 to -7.78). Additionally, pramipexole is superior to ropinirole in alleviating symptoms of RLS (MD -2.52, 95% CI -4.69 to -0.35). Moreover, iron supplement alleviates RLS symptoms significantly compared with placebo in patient with iron deficiency (MD -5.15, 95% CI -8.99 to -1.31), but not for RLS patients with normal serum ferritin level (MD -2.22, 95% CI -6.99 to 2.56). For primary RLS, these drugs are also effective, while there is insufficient data to analyze drug efficacy in secondary RLS. We analyzed risk of common adverse effects of drugs including nausea, somnolence, fatigue, headache and nasopharyngitis. Alpha-2-delta ligands and DAs are favorable choices for both primary and secondary RLS because of their significant efficacy and good tolerability. Iron supplement can significantly alleviate symptoms of RLS patients with iron deficiency than placebo. We recommend gabapentin, gabapentin enacarbil, and pregabalin for clinicians for first consideration mainly because that they rarely cause augmentation. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with above drugs.
PubMed: 34764852
DOI: 10.3389/fnins.2021.751643 -
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 -
Journal of Internal Medicine May 2020Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of... (Meta-Analysis)
Meta-Analysis
Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.
Topics: Analgesics; Analgesics, Opioid; Chronic Pain; Drug Therapy; Humans; Observational Studies as Topic; Pain Management
PubMed: 32100394
DOI: 10.1111/joim.13026