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The Cochrane Database of Systematic... Oct 2017Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'.
OBJECTIVES
To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults.
METHODS
We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework.
MAIN RESULTS
We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity.
AUTHORS' CONCLUSIONS
A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Review Literature as Topic; Time Factors
PubMed: 29084357
DOI: 10.1002/14651858.CD012509.pub2 -
Annals of Internal Medicine Nov 2020Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.
PURPOSE
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
STUDY SELECTION
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries.
DATA EXTRACTION
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
LIMITATIONS
Only English-language studies were included. The number of head-to-head comparisons was limited.
CONCLUSION
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
PRIMARY FUNDING SOURCE
National Safety Council. (PROSPERO: CRD42018094412).
Topics: Acetaminophen; Acute Pain; Administration, Oral; Administration, Topical; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Comparative Effectiveness Research; Diclofenac; Drug Eruptions; Gastrointestinal Diseases; Humans; Musculoskeletal System; Nervous System Diseases; Network Meta-Analysis; Patient Satisfaction; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 32805127
DOI: 10.7326/M19-3601 -
Social Psychiatry and Psychiatric... Apr 2022This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids. (Review)
Review
PURPOSE
This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids.
METHODS
The protocol was published in Open Science Framework. We used the PECOS framework to frame the review question. Studies published between January 1, 2000, and January 4, 2021, from North America, Europe, the United Kingdom, Australia, and New Zealand were systematically identified and screened through searching electronic databases, citations, and by contacting experts. Risk of bias assessments were performed. Data were synthesized using the lumping technique.
RESULTS
Overall, 6512 records were screened and 38 were selected for inclusion. 37 of the 38 studies included in this review show a connection between at least one aspect of mental disorder and opioid overdose. The largest body of evidence exists for internalizing disorders generally and mood disorders specifically, followed by anxiety disorders, although there is also moderate evidence to support the relationship between thought disorders (e.g., schizophrenia, bipolar disorder) and opioid overdose. Moderate evidence also was found for the association between any disorder and overdose.
CONCLUSION
Nearly all reviewed studies found a connection between mental disorder and overdose, and the evidence suggests that having mental disorder is associated with experiencing fatal and non-fatal opioid overdose, but causal direction remains unclear.
Topics: Analgesics, Opioid; Drug Overdose; Europe; Humans; Opiate Overdose; Psychotic Disorders
PubMed: 34796369
DOI: 10.1007/s00127-021-02199-2 -
Journal of Perianesthesia Nursing :... Dec 2022Nonopioid analgesics are commonly used to augment or replace opioids in the perioperative setting. Perianesthesia nurses must consider timing and appropriateness when... (Review)
Review
PURPOSE
Nonopioid analgesics are commonly used to augment or replace opioids in the perioperative setting. Perianesthesia nurses must consider timing and appropriateness when administering these medications to patients in the preoperative area or the postanesthesia care unit, particularly when other medications with sedative effects are being given. Gabapentin, originally proposed as an anticonvulsant medication, promotes analgesia and reduces risk for postoperative nausea and vomiting. This review examines the effect of gabapentin on postoperative pain.
DESIGN
A systematic review.
METHODS
CINAHL, PubMed, and Cochrane Review databases were searched to find a total of 93 sources that examined gabapentin and postoperative pain. After applying inclusion and exclusion criteria, four randomized controlled trials (RCT) were reviewed. Postoperative pain within the 24 hours of surgery was measured as the primary outcome using the visual analog scale in all sources FINDINGS: Three of the four reviewed RCTs determined gabapentin was both statistically and clinically significant in reducing postoperative pain, and all four sources showed a reduction in opioid consumption during the immediate postoperative period, which promoted patient satisfaction.
CONCLUSIONS
Further study of gabapentin and postoperative pain is needed employing rigorous and robust methodology and diversity of the sample selections.
Topics: Humans; Gabapentin; Analgesics, Opioid; Analgesics; Pain, Postoperative; Anesthesia
PubMed: 36100525
DOI: 10.1016/j.jopan.2022.04.008 -
Drugs Jul 2021We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical...
We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Liver Failure; Pain; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 34196947
DOI: 10.1007/s40265-021-01515-z -
Neuropsychopharmacology : Official... Aug 2017Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study... (Meta-Analysis)
Meta-Analysis Review
Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED of morphine alone. In addition, the ED for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.
Topics: Analgesics, Opioid; Animals; Cannabinoids; Drug Synergism; Humans; Pain
PubMed: 28327548
DOI: 10.1038/npp.2017.51 -
Therapeutic Drug Monitoring Feb 2021The culmination of the widespread overprescription of opioids, a resurgence of heroin use, and increased accessibility and use of illicit synthetic opioids is commonly...
BACKGROUND
The culmination of the widespread overprescription of opioids, a resurgence of heroin use, and increased accessibility and use of illicit synthetic opioids is commonly referred to as the opioid epidemic in North America.
METHODS
This article is not intended to provide a comprehensive systematic literature review, but rather summarized recent publications and online governmental reports and datasets for English-written literature primarily published between January 1, 2015 and July 1, 2020.
RESULTS
In both the United States and Canada, opioids represent one of the most widely prescribed classes of medications. According to the US Centers for Disease Control and Prevention (CDC), an unprecedented increase in the use of opioid pain relievers has led to one of the worst drug overdose epidemics in US history and continues to be an ongoing major public health crisis based on recent Centers for Disease Control and Prevention mortality data, where almost two-thirds of all overdose deaths still involve opioids, including heroin and illicit opioids. In addition to the high mortality rates in both the United States and Canada, there has also been an increase in emergency department visits for nonmedical use of opioid pain relievers, along with additional individuals seeking treatment for opioid addiction, and a rise in neonatal abstinence syndrome.
CONCLUSIONS
This article highlights the history, underlying issues, ongoing national regulatory efforts, and future strategies and therapies to help mitigate the opioid crisis in North America.
Topics: Analgesics, Opioid; Canada; Drug Overdose; Humans; Opioid Epidemic; Opioid-Related Disorders; United States
PubMed: 33337587
DOI: 10.1097/FTD.0000000000000817 -
American Journal of Therapeutics 2015The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the... (Review)
Review
The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.
Topics: Acute Disease; Analgesics, Opioid; Drug Tolerance; Humans; Hyperalgesia; Pain Threshold; Piperidines; Remifentanil
PubMed: 25830866
DOI: 10.1097/MJT.0000000000000019 -
BMJ Open Jan 2024The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021.
STUDY SELECTION
Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks.
DATA EXTRACTION AND SYNTHESIS
Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings.
RESULTS
Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59).
CONCLUSIONS
Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.
PROSPERO REGISTRATION NUMBER
CRD42020185184.
Topics: Humans; Analgesics, Opioid; Bayes Theorem; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 38171632
DOI: 10.1136/bmjopen-2022-068182 -
Patient Education and Counseling Sep 2022To determine the role of perioperative protocolized opioid-specific patient education on opioid consumption for individuals undergoing surgical procedures. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the role of perioperative protocolized opioid-specific patient education on opioid consumption for individuals undergoing surgical procedures.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) that compared protocolized perioperative opioid-specific patient education to the usual care for adult individuals undergoing surgical interventions. The standardized mean difference (SMD) was used to represent continuous outcomes while the risk ratio (RR) was used to represent dichotomous outcomes.
RESULTS
In total, 15 RCTs that enrolled 2546 participants were deemed eligible. Protocolized opioid-specific patient education showed a significant reduction in postoperative opioid consumption and postoperative pain score compared to usual care (SMD= -0.15, 95% confidence interval [CI]: -0.28 to -0.03 and SMD= -0.17, 95% CI: -0.28 to -0.06, respectively). No significant difference was found between the protocolized opioid-specific patient education and the usual care in terms of the number of refill requests (RR=0.82, 95% CI: 0.50-1.34), patients with opioid leftovers (RR=0.92, 95% CI: 0.78-1.08), and patients taking opioids after hospital discharge.
CONCLUSIONS
This meta-analysis demonstrated that protocolized opioid-specific patient education significantly reduces postoperative opioid consumption and pain score but has no influence on the number of opioid refill requests, opioid leftovers, and opioid use after hospital discharge.
PRACTICE IMPLICATIONS
Healthcare professionals may offer opioid-related educational sessions for the surgical patients during the perioperative period through a video-based material that emphasizes the role of alternative analgesics to opioids, patients' expectations about the post-operative pain, and the potential side effects of opioid consumptions.
Topics: Adult; Analgesics, Opioid; Humans; Pain, Postoperative; Patient Education as Topic
PubMed: 35537899
DOI: 10.1016/j.pec.2022.04.016