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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 non-significant 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 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
The Journal of Arthroplasty Feb 2024Pain is challenging after recovery from total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures, and patients often receive prescription opioids....
BACKGROUND
Pain is challenging after recovery from total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures, and patients often receive prescription opioids. However, opioid consumption by patients remains unclear, and unused opioids may lead to risks including misuse and diversion. The objective of this systematic review and meta-analysis was to compare prescription size versus patient-reported consumption of opioids after discharge following TKA and THA.
METHODS
PubMed and Embase were systematically searched for publications published between 2015 and 2022 on patient-reported consumption of opioids after TKA and THA. The primary outcome was opioid use in oxycodone 5-mg equivalents. Team members independently reviewed studies for screening, inclusion, data extraction, and risk of bias.
RESULTS
Among the 17 included studies (15 TKA and 11 THA), discharge opioid prescribing exceeded consumption for both TKA (88.4 versus 65.0 pills at 6 weeks) and THA (64.0 versus 29.8 pills at 12 weeks). For both TKA and THA, the range of opioids prescribed varied significantly, by 1.6-fold for TKA and 2.8-fold for THA. Most studies reported pain outcomes (89%) and the use of nonopioid medications (72%). Of the 4 studies offering prescribing recommendations, the amounts ranged from 50 to 104 pills for TKA and 30 to 45 pills for THA.
CONCLUSIONS
Opioid prescribing exceeds the amount consumed following TKA and THA. These findings serve as a call to action to tailor prescribing guidelines to how much patients actually consume while emphasizing the use of nonopioid medications to better optimize recovery from surgery.
PubMed: 38336301
DOI: 10.1016/j.arth.2024.01.063 -
World Journal of Plastic Surgery 2023We aimed to investigate the pharmacological and non-pharmacological interventions used for mitigating pain. (Review)
Review
BACKGROUND
We aimed to investigate the pharmacological and non-pharmacological interventions used for mitigating pain.
METHODS
We integrated randomized controlled trials (RCTs) chosen from PubMed, Google scholar, and Scopus and aimed at assessing the effectiveness of one or multiple variants of Non-steroidal anti-inflammatory drugs (NSAIDs), as well as Narcotic analgesics, compared to corticosteroids, curcumin, hyaluronic acid, and antibiotics. In addition, trials utilizing NSAIDs, including Rofecoxib, which have been withdrawn from market circulation, were deemed ineligible for inclusion.
RESULT
A total of 9 RCTs were evaluated in this study, and the patients' postoperative pain was assessed using the visual analog scale (VAS) and the time measurement. Moreover, there were various approaches to alleviating pain and discomfort.
CONCLUSION
The administration of ibuprofen prior to surgery leads to a marked reduction in pain. Pharmacological interventions, such as the administration of dexamethasone and oxycodone, alongside non-pharmacological interventions, such as laser therapy, have been shown to effectively alleviate the discomfort resulting from surgical procedures on the jaw and face.
PubMed: 38130382
DOI: 10.52547/wjps.12.2.3 -
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 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Frontiers in Pharmacology 2023To systematically assess and rank the efficacy of opioid medications for traumatic pain in the emergency department in terms of pain relief, adverse events and rescue...
To systematically assess and rank the efficacy of opioid medications for traumatic pain in the emergency department in terms of pain relief, adverse events and rescue analgesia. Four databases were systematically searched until 26 September 2022: PubMed, Embase, Cochrane Library, and Web of Science. Outcomes were pain relief, adverse events (dizziness, hypotension, pruritus, sedation), and rescue analgesia. For each outcome, network plots were drawn to exhibit direct and indirect comparisons, and rank probabilities were utilized to rank the efficacy of different opioids. Twenty studies of 3,040 patients were eligible for this network meta-analysis. According to the rank probabilities, the top three analgesic medications for pain relief may be sufentanil (78.29% probability of ranking first), buprenorphine (48.54% probability of ranking second) and fentanyl (53.25% probability of ranking third); buprenorphine (31.20%), fentanyl (20.14%) and sufentanil (21.55%) were least likely to cause dizziness; the top three analgesic medications which were least likely to cause hypotension were buprenorphine (81.64%), morphine (45.02%) and sufentanil (17.27%); butorphanol (40.56%), morphine (41.11%) and fentanyl (14.63%) were least likely to cause pruritus; the top three medications which were least likely to cause sedation were hydrocodone + acetaminophen (97.92%), morphine (61.85%) and butorphanol (55.24%); patients who received oxycodone (83.64%), butorphanol (38.31%) and fentanyl (25.91%) were least likely to need rescue analgesia in sequence. Sufentanil, buprenorphine and fentanyl may be superior to other opioid medications in terms of pain relief and the incidence of dizziness, hypotension and pruritus, which might be selected as opioid analgesics for traumatic pain in the emergency setting.
PubMed: 37576822
DOI: 10.3389/fphar.2023.1209131 -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
BMC Urology Mar 2023Catheter-related bladder discomfort (CRBD) is a common postoperative bladder pain syndrome. Many drugs and interventions for managing CRBD have been studied, but their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Catheter-related bladder discomfort (CRBD) is a common postoperative bladder pain syndrome. Many drugs and interventions for managing CRBD have been studied, but their comparative effectiveness remains controversial. We made a study to assess the comparative effectiveness of interventions included Ketorolac, Lidocaine, Chlorpheniramine, Gabapentin, Magnesium, Nefopam, Oxycodone, Parecoxib, Solifenacin, Tolterodine, Bupivancaine, Dexmedetomidine, Hyoscine N-butyl bromide, Ketamine, Penile nerve block on urological postoperative CRBD.
METHODS
We performed a network meta-analysis via Aggregate Data Drug Inormation System software included 18 studies with 1816 patients and assessed the risk of bias by Cochrane Collaboration tool. The incidence of moderate to severe CRBD at 0, 1, and 6 h after surgery and the incidence severe CRBD at 1 h after surgery were compared.
RESULT
The number of best rank is 0.48(Nefopam) and 0.22(Nefopam) in the incidence of moderate to severe CRBD at 1 h and incidence severe CRBD at 1 h. More than half of studies at unclear or high risk of bias.
CONCLUSION
Nefopam reduced the incidence of CRBD and prevented severe events, but limited by the small number of studies for each intervention and heterogeneous patients.
Topics: Humans; Network Meta-Analysis; Nefopam; Urinary Bladder; Urinary Catheters; Cystitis, Interstitial
PubMed: 36869313
DOI: 10.1186/s12894-023-01195-9 -
Journal of Dental Research Apr 2023This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline,... (Meta-Analysis)
Meta-Analysis
This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
Topics: Adult; Humans; Acetaminophen; Ibuprofen; Oxycodone; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Pain, Postoperative; Analgesics, Opioid; Tooth Extraction; Acute Pain
PubMed: 36631957
DOI: 10.1177/00220345221139230