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Lancet (London, England) Oct 2019We summarise the evidence for medicinal uses of opioids, harms related to the extramedical use of, and dependence on, these drugs, and a wide range of interventions used...
We summarise the evidence for medicinal uses of opioids, harms related to the extramedical use of, and dependence on, these drugs, and a wide range of interventions used to address these harms. The Global Burden of Diseases, Injuries, and Risk Factors Study estimated that in 2017, 40·5 million people were dependent on opioids (95% uncertainty interval 34·3-47·9 million) and 109 500 people (105 800-113 600) died from opioid overdose. Opioid agonist treatment (OAT) can be highly effective in reducing illicit opioid use and improving multiple health and social outcomes-eg, by reducing overall mortality and key causes of death, including overdose, suicide, HIV, hepatitis C virus, and other injuries. Mathematical modelling suggests that scaling up the use of OAT and retaining people in treatment, including in prison, could avert a median of 7·7% of deaths in Kentucky, 10·7% in Kiev, and 25·9% in Tehran over 20 years (compared with no OAT), with the greater effects in Tehran and Kiev being due to reductions in HIV mortality, given the higher prevalence of HIV among people who inject drugs in those settings. Other interventions have varied evidence for effectiveness and patient acceptability, and typically affect a narrower set of outcomes than OAT does. Other effective interventions focus on preventing harm related to opioids. Despite strong evidence for the effectiveness of a range of interventions to improve the health and wellbeing of people who are dependent on opioids, coverage is low, even in high-income countries. Treatment quality might be less than desirable, and considerable harm might be caused to individuals, society, and the economy by the criminalisation of extramedical opioid use and dependence. Alternative policy frameworks are recommended that adopt an approach based on human rights and public health, do not make drug use a criminal behaviour, and seek to reduce drug-related harm at the population level.
Topics: Analgesics, Opioid; Drug Overdose; Global Health; Health Knowledge, Attitudes, Practice; Humans; Opioid-Related Disorders; Prevalence; Risk Factors
PubMed: 31657732
DOI: 10.1016/S0140-6736(19)32229-9 -
Chiropractic & Manual Therapies May 2022To identify and descriptively compare medication recommendations among low back pain (LBP) clinical practice guidelines (CPG). (Review)
Review
OBJECTIVE
To identify and descriptively compare medication recommendations among low back pain (LBP) clinical practice guidelines (CPG).
METHODS
We searched PubMed, Cochrane Database of Systematic Review, Index to Chiropractic Literature, AMED, CINAHL, and PEDro to identify CPGs that described the management of mechanical LBP in the prior five years. Two investigators independently screened titles and abstracts and potentially relevant full text were considered for eligibility. Four investigators independently applied the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for critical appraisal. Data were extracted for pharmaceutical intervention, the strength of recommendation, and appropriateness for the duration of LBP.
RESULTS
316 citations were identified, 50 full-text articles were assessed, and nine guidelines with global representation met the eligibility criteria. These CPGs addressed pharmacological treatments with or without non-pharmacological treatments. All CPGS focused on the management of acute, chronic, or unspecified duration of LBP. The mean overall AGREE II score was 89.3% (SD 3.5%). The lowest domain mean score was for applicability, 80.4% (SD 5.2%), and the highest was Scope and Purpose, 94.0% (SD 2.4%). There were ten classifications of medications described in the included CPGs: acetaminophen, antibiotics, anticonvulsants, antidepressants, benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral corticosteroids, skeletal muscle relaxants (SMRs), and atypical opioids.
CONCLUSIONS
Nine CPGs, included ten medication classes for the management of LBP. NSAIDs were the most frequently recommended medication for the treatment of both acute and chronic LBP as a first line pharmacological therapy. Acetaminophen and SMRs were inconsistently recommended for acute LBP. Meanwhile, with less consensus among CPGs, acetaminophen and antidepressants were proposed as second-choice therapies for chronic LBP. There was significant heterogeneity of recommendations within many medication classes, although oral corticosteroids, benzodiazepines, anticonvulsants, and antibiotics were not recommended by any CPGs for acute or chronic LBP.
Topics: Acetaminophen; Adrenal Cortex Hormones; Analgesics, Opioid; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents; Benzodiazepines; Humans; Low Back Pain; Pharmaceutical Preparations
PubMed: 35562756
DOI: 10.1186/s12998-022-00435-3 -
Anesthesia and Analgesia Jul 2023Pain after thoracic surgery is of moderate-to-severe intensity and can cause increased postoperative distress and affect functional recovery. Opioids have been central...
Pain after thoracic surgery is of moderate-to-severe intensity and can cause increased postoperative distress and affect functional recovery. Opioids have been central agents in treating pain after thoracic surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure, thus preventing the risk of developing persistent postoperative pain. This practice advisory is part of a series developed by the Society of Cardiovascular Anesthesiologists (SCA) Quality, Safety, and Leadership (QSL) Committee's Opioid Working Group. It is a systematic review of existing literature for various interventions related to the preoperative and intraoperative pain management of thoracic surgical patients and provides recommendations for providers caring for patients undergoing thoracic surgery. This entails developing customized pain management strategies for patients, which include preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various thoracic surgical procedures. The literature related to this field is emerging and will hopefully provide more information on ways to improve clinically relevant patient outcomes and promote recovery in the future.
Topics: Humans; Pain Management; Analgesics, Opioid; Pain, Postoperative; Opioid-Related Disorders; Thoracic Surgical Procedures; Analgesics
PubMed: 37079466
DOI: 10.1213/ANE.0000000000006441 -
Expert Opinion on Pharmacotherapy Jan 2021Treating chronic low back pain (LBP) can be challenging, and the most effective pharmacological therapy is controversial. The present systematic review investigated the...
INTRODUCTION
Treating chronic low back pain (LBP) can be challenging, and the most effective pharmacological therapy is controversial. The present systematic review investigated the efficacy of various pharmacological compounds to achieve pain relief and improve disability in chronic LBP patients. The present study focused on acetaminophen, amoxicillin, flupirtine, baclofen, tryciclic antidepressants (TCAs), duloxetine, topiramate, gabapentinoids, non-steroid anti-inflammatory drugs (NSAIDs) and opioids.
AREAS COVERED
All randomized clinical trials comparing two or more drug treatments for chronic low back pain were accessed. Studies reporting outcomes concerning patients with neurologic or mechanic, specific or aspecific low back pain with or without radiculopathy were included. LBP was considered chronic if pain had lasted more than 6 weeks. Data from 47 articles (9007 patients: mean age: 52.62 ± 7.0 years; mean BMI: 28.26 ± 2.8; mean follow-up: 3.23 ± 3.2 months) were obtained.
EXPERT OPINION
According to published level I evidence, only baclofen, duloxetine, NSAIDs, and opiates showed to improve pain and disability levels in patients with LBP. However, the patients' demographics are heterogeneous, and the results must be interpreted with caution and in the light of possible adverse events connected to the use of these drugs.
Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Chronic Pain; Humans; Low Back Pain; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 32885995
DOI: 10.1080/14656566.2020.1817384 -
BMJ Open Jul 2021To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.
DESIGN
Systematic review.
DATA SOURCES
CENTRAL, EMBASE and MEDLINE.
MAIN OUTCOMES AND MEASURES
Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.
STUDY SELECTION CRITERIA AND METHODS
We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome.
RESULTS
Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) -3.4 milligram morphine equivalent (MME); 95% CI (CI) -12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD -0.18 cm; 95% CI -0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD -0.22 cm; 95% CI -0.4 to -0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD -1%; 95% CI -4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD -22.5 MME; 95% CI -43.06 to -1.97).
CONCLUSION
Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.CRD42018091098.
Topics: Analgesics, Opioid; Cannabinoids; Chronic Pain; Humans; Medical Marijuana; Observational Studies as Topic; Randomized Controlled Trials as Topic; Vomiting
PubMed: 34321302
DOI: 10.1136/bmjopen-2020-047717 -
Pain Feb 2023Neuropathic pain causes substantial morbidity and healthcare utilization. Monotherapy with antidepressants or anticonvulsants often fails to provide relief. Combining... (Meta-Analysis)
Meta-Analysis
Neuropathic pain causes substantial morbidity and healthcare utilization. Monotherapy with antidepressants or anticonvulsants often fails to provide relief. Combining different drugs sometimes provides improved analgesia and/or tolerability. More than half of patients receive 2 or more analgesics, and combination trials continue to emerge. This review comprehensively searched CENTRAL, MEDLINE, and EMBASE for relevant trials. Included studies are double-blind randomized controlled trials evaluating combinations of 2 or more drugs vs placebo or at least one monotherapy in adults with neuropathic pain. Outcomes included measures of efficacy and adverse effects. Risk of bias was assessed. Meta-analyses compared combination to monotherapy wherever 2 or more similar studies were available. Forty studies (4741 participants) were included. Studies were heterogenous with respect to various characteristics, including dose titration methods and administration (ie, simultaneous vs sequential) of the combination. Few combinations involved a nonsedating drug, and several methodological problems were identified. For opioid-antidepressant, opioid-gabapentinoid, and gabapentinoid-antidepressant combinations, meta-analyses failed to demonstrate superiority over both monotherapies. In general, adverse event profiles were not substantially different for combination therapy compared with monotherapy. Despite widespread use and a growing number of trials, convincing evidence has not yet emerged to suggest superiority of any combination over its respective monotherapies. Therefore, implementing combination therapy-as second- or third-line treatment-in situations where monotherapy is insufficient, should involve closely monitored individual dosing trials to confirm safety and overall added benefit. Further research is needed, including trials of combinations involving nonsedating agents, and to identify clinical settings and specific combinations that safely provide added benefit.
Topics: Adult; Humans; Analgesics, Opioid; Neuralgia; Analgesics; Antidepressive Agents; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 35588148
DOI: 10.1097/j.pain.0000000000002688 -
The Journal of Orthopaedic and Sports... Apr 2022To compare the effectiveness of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and exercise therapy for knee osteoarthritis pain. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the effectiveness of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and exercise therapy for knee osteoarthritis pain.
DESIGN
Systematic review with network meta-analysis.
LITERATURE SEARCH
We searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to April 15, 2021. Web of Science was used for citation tracking.
STUDY SELECTION CRITERIA
Randomized controlled trials comparing exercise therapy, NSAIDs, and opioids in any combination for knee osteoarthritis pain.
DATA SYNTHESIS
Network meta-analysis comparing exercise therapy, NSAIDs, opioids, and placebo/control for knee osteoarthritis pain. Additional trials from previous reviews were included to create the external placebo/control anchor.
RESULTS
We included 13 trials (1398 patients) with direct comparisons, supplemented with data from 101 additional trials. The treatment effect of NSAIDs for knee osteoarthritis pain was similar to that of opioids (standardized mean difference [SMD], 0.02; 95% confidence interval [CI], -0.14 to 0.18; Grading of Recommendations, Assessment, Development and Evaluations [GRADE]: low certainty). Exercise therapy had a larger effect than NSAIDs (SMD, 0.54; 95% CI, 0.19 to 0.89; GRADE: very low certainty). No estimate could be made for exercise vs opioids due to the lack of studies. Exercise therapy ranked as the "best" intervention in the network meta-analysis, followed by NSAIDs, opioids, and placebo/control intervention (GRADE: low certainty).
CONCLUSION
Exercise therapy ranked as the best treatment for knee osteoarthritis pain, followed by NSAIDs and opioids. The difference between treatments was small and likely not clinically relevant, and the overall confidence in the ranking was low. The results highlight the limited evidence for comparative effectiveness between exercise therapy, NSAIDs, and opioids for knee osteoarthritis pain. .
Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Exercise Therapy; Humans; Network Meta-Analysis; Osteoarthritis, Knee; Pain
PubMed: 35442752
DOI: 10.2519/jospt.2022.10490 -
Emergency Medicine Journal : EMJ Jul 2023Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to... (Meta-Analysis)
Meta-Analysis
Comparison of intravenous paracetamol (acetaminophen) to intravenously or intramuscularly administered non-steroidal anti-inflammatory drugs (NSAIDs) or opioids for patients presenting with moderate to severe acute pain conditions to the ED: systematic review and meta-analysis.
OBJECTIVE
Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to provide analgesia for patients with moderate to severe pain. This systematic review and meta-analysis evaluated the level of analgesia provided by intravenous paracetamol (IVP) alone compared with NSAIDs (intravenous or intramuscular), or opioids (intravenous) alone in adults attending the ED with acute pain.
METHODS
Two authors independently searched PubMed (MEDLINE), Web of Science, Embase (OVID), Cochrane Library, SCOPUS and Google Scholar (3 March 2021-20 May 2022) for randomised trials without any language or date restriction. Clinical trials were evaluated using the Risk of Bias V.2 tool. The primary outcome was mean difference (MD) for pain reduction at 30 min (T30) post analgesia delivery. The secondary outcomes were MD in pain reduction at 60, 90 and 120 min; the need for rescue analgesia; and the occurrence of adverse events (AEs).
RESULTS
Twenty-seven trials (5427 patients) were included in the systematic review and 25 trials (5006 patients) in the meta-analysis. There was no significant difference in pain reduction at T30 between the IVP group and opioids (MD -0.13, 95% CI -1.49 to 1.22) or IVP and NSAIDs (MD -0.27, 95% CI -1.0 to 1.54. There was also no difference at 60 min, IVP group versus opioid group (MD -0.09, 95% CI -2.69 to 2.52) or IVP versus NSAIDs (MD 0.51, 95% CI 0.11 to 0.91). The quality of the evidence using Grading of Recommendations, Assessments, Development and Evaluations methodology was low for MD in pain scores.The need for rescue analgesia at T30 was significantly higher in the IVP group compared with the NSAID group (risk ratio (RR): 1.50, 95% CI 1.23 to 1.83), with no difference found between the IVP group and the opioid group (RR: 1.07, 95% CI 0.67 to 1.70). AEs were 50% lower in the IVP group compared with the opioid group (RR: 0.50, 95% CI 0.40 to 0.62), whereas no difference was observed in the IVP group compared with the NSAID group (RR: 1.30, 95% CI 0.78 to 2.15).
CONCLUSION
In patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable alternative.
PROSPERO REGISTRATION NUMBER
CRD42021240099.
Topics: Adult; Humans; Acetaminophen; Acute Pain; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Administration, Intravenous; Injections, Intramuscular; Emergency Service, Hospital; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 37173122
DOI: 10.1136/emermed-2022-212869 -
American Journal of Obstetrics and... Jul 2023This meta-analysis was conducted to (1) assess the quantity and dose of perioperatively dispensed opioids for benign hysterectomy by procedure route and (2) identify the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This meta-analysis was conducted to (1) assess the quantity and dose of perioperatively dispensed opioids for benign hysterectomy by procedure route and (2) identify the predictors of persistent opioid use after the procedure.
DATA SOURCES
PubMed, Web of Science, and Embase were systematically searched from study inception to 25 March 2022.
STUDY ELIGIBILITY CRITERIA
Studies reporting data on opioid dispensing among patients undergoing benign hysterectomy were considered eligible. The primary outcome was the dosage of opioids dispensed perioperatively (from 30 preoperative days to 21 postoperative days). The secondary outcome was the predictors of persistent opioid use after benign hysterectomy (from 3 months to 3 years postoperatively). Total opioid dispensing was measured in morphine milligram equivalents units.
METHODS
The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals.
RESULTS
A total of 8 studies presenting data on 377,569 women undergoing benign hysterectomy were included. Of these women, 83% (95% confidence interval, 81-84) were dispensed opioids during the perioperative period. The average amount of perioperatively dispensed opioids was 143.5 morphine milligram equivalents (95% confidence interval, 40-247). Women undergoing vaginal hysterectomy were dispensed a significantly lower amount of opioids than those undergoing laparoscopic or abdominal hysterectomies. The overall rate of persistent opioid use after benign hysterectomy was 5% (95% confidence interval, 2-8). Younger patient age (odds ratio, 1.38; 95% confidence interval, 1.17-1.63), smoking history (odds ratio, 1.87; 95% confidence interval, 1.67-2.10), alcohol use (odds ratio, 3.16; 95% confidence interval, 2.34-4.27), back pain (odds ratio, 1.50; 95% confidence interval, 1.10-2.05), and fibromyalgia (odds ratio, 1.60; 95% confidence interval, 1.39-1.83) were significantly associated with a higher risk of persistent opioid use after benign hysterectomy. However, there was no significant effect of hysterectomy route and operative complexity on persistent opioid use postoperatively.
CONCLUSION
Perioperative opioid dispensing was significantly dependent on the route of hysterectomy, with the lowest dispensed morphine milligram equivalents of opioids for vaginal hysterectomy and the highest for abdominal hysterectomy. Nevertheless, hysterectomy route did not significantly predict persistent opioid use postoperatively, whereas younger age, smoking, alcohol use, back pain, and fibromyalgia were significantly associated with persistent opioid use.
Topics: Humans; Female; Analgesics, Opioid; Fibromyalgia; Pain, Postoperative; Hysterectomy; Opioid-Related Disorders; Morphine Derivatives
PubMed: 36539027
DOI: 10.1016/j.ajog.2022.12.015 -
Pharmacological Reviews Jan 2022A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies... (Review)
Review
A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration, and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones' role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and not a priori designed to detect sex differences. Additionally, imaging studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving but not cue- or cocaine-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or opioids in rodent models. SIGNIFICANCE STATEMENT: This systematic review summarizes clinical and preclinical studies on sex differences in psychostimulant and opioid craving and relapse. Results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. Results of preclinical studies reviewed provide evidence for sex differences in reinstatement and incubation of cocaine seeking but not for reinstatement or incubation of methamphetamine or opioid seeking.
Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Craving; Extinction, Psychological; Female; Humans; Male; Recurrence; Self Administration; Sex Characteristics
PubMed: 34987089
DOI: 10.1124/pharmrev.121.000367