-
European Journal of Clinical... Mar 2024Considering the conflicting effects of bupropion on parameters related to cardiovascular system including blood pressure and inflammation, in this meta-analysis study,... (Meta-Analysis)
Meta-Analysis Review
The effects of bupropion alone and combined with naltrexone on blood pressure and CRP concentration: A systematic review and meta-regression analysis of randomized controlled trials.
BACKGROUND
Considering the conflicting effects of bupropion on parameters related to cardiovascular system including blood pressure and inflammation, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on systolic (SBP) and diastolic blood pressure (DBP) and C-reactive protein (CRP).
METHODS
Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the BP and CRP. Pooled weighted mean difference and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes.
RESULTS
The pooled findings showed that that bupropion alone or in combination with naltrexone would significantly increase SBP (weighted mean difference (WMD): 1.34 mmHg, 95% CI: 0.38-2.29) and DBP (WMD: 0.93 mmHg, 95% CI 0.88-0.99) as well as decrease CRP (WMD: -0.89 mg/L, 95% CI -1.09 to -0.70). The findings of the subgroup also show the greater effect of bupropion on blood pressure (SBP and DBP) increase in a dose greater than 360 mg and a duration of intervention less equal to 26 weeks. In addition, the subgroup analysis showed that changes in SBP after receiving bupropion together with naltrexone were more compared to bupropion alone.
CONCLUSIONS
The addition of combination therapies such as bupropion and naltrexone can significantly improve CRP levels. However, its effect on blood pressure requires proper management of this drug.
Topics: Humans; Blood Pressure; C-Reactive Protein; Naltrexone; Bupropion; Randomized Controlled Trials as Topic; Regression Analysis; Hypertension
PubMed: 37924302
DOI: 10.1111/eci.14118 -
Neurogastroenterology and Motility Dec 2023Constipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally-active mu-opioid receptor antagonists (PAMORAs) are... (Meta-Analysis)
Meta-Analysis
Peripherally-active mu-opioid receptor antagonists for constipation in critically ill patients receiving opioids: A case-series and a systematic review and meta-analysis of the literature.
BACKGROUND
Constipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally-active mu-opioid receptor antagonists (PAMORAs) are approved for opioid-induced constipation, but information on their efficacy and safety in critically ill patients is limited. We present a single-center, retrospective, case-series of the use of naldemedine for opioid-associated constipation, and we systematically reviewed the use of PAMORAs in critically ill patients.
METHODS
Case-series included consecutive mechanically-ventilated patients; constipation was defined as absence of bowel movements for >3 days. Naldemedine was administered after failure of the local laxation protocol. Systematic review: PubMed was searched for studies of PAMORAs to treat opioid-induced constipation in adult critically ill patients.
PRIMARY OUTCOMES
time to laxation, and number of patients laxating at the shortest follow-up.
SECONDARY OUTCOMES
gastric residual volumes and adverse events.
KEY RESULTS
A total of 13 patients were included in the case-series; the most common diagnosis was COVID-19 ARDS. Patients had their first bowel movement 1 [0;2] day after naldemedine. Daily gastric residual volume was 725 [405;1805] before vs. 250 [45;1090] mL after naldemedine, p = 0.0078. Systematic review identified nine studies (two RCTs, one prospective case-series, three retrospective case-series and three case-reports). Outcomes were similar between groups, with a trend toward a lower gastric residual volume in PAMORAs group.
CONCLUSIONS & INFERENCES
In a highly-selected case-series of patients with refractory, opioid-associated constipation, naldemedine was safe and associated to reduced gastric residuals and promoting laxation. In the systematic review and meta-analysis, the use of PAMORAs (mainly methylnaltrexone) was safe and associated with a reduced intolerance to enteral feeding but no difference in the time to laxation.
Topics: Adult; Humans; Narcotic Antagonists; Analgesics, Opioid; Constipation; Opioid-Induced Constipation; Retrospective Studies; Critical Illness; Naltrexone; Laxatives
PubMed: 37869768
DOI: 10.1111/nmo.14694 -
European Journal of Psychotraumatology 2023The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system.
OBJECTIVE
To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders.
METHOD
The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases.
RESULTS
1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 ( < .001)] and there may have been publication bias.
CONCLUSIONS
Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate - large effect size in reducing these symptoms.
Topics: Humans; Narcotic Antagonists; Naltrexone; Naloxone; Dissociative Disorders
PubMed: 37860852
DOI: 10.1080/20008066.2023.2265184 -
Scientific Reports Oct 2023Rhabdomyolysis is a potentially life-threatening condition induced by diverse mechanisms including drugs and toxins. We aimed to investigate the incidence of... (Meta-Analysis)
Meta-Analysis
Rhabdomyolysis is a potentially life-threatening condition induced by diverse mechanisms including drugs and toxins. We aimed to investigate the incidence of rhabdomyolysis occurrence in intoxicated patients with psychoactive substances. In this review, three databases (PubMed, Scopus, Web of Science) and search engine (Google Scholar) were searched by various keywords. After the screening of retrieved documents, related data of included studies were extracted and analyzed with weighted mean difference (WMD) in random effect model. The highest incidence of rhabdomyolysis was observed in intoxication with heroin (57.2 [95% CI 22.6-91.8]), amphetamines (30.5 [95% CI 22.6-38.5]), and cocaine (26.6 [95% CI 11.1-42.1]). The pooled effect size for blood urea nitrogen (WMD = 8.78, p = 0.002), creatinine (WMD = 0.44, p < 0.001), and creatinine phosphokinase (WMD = 2590.9, p < 0.001) was high in patients with rhabdomyolysis compared to patients without rhabdomyolysis. Our results showed a high incidence of rhabdomyolysis induced by psychoactive substance intoxication in ICU patients when compared to total wards. Also, the incidence of rhabdomyolysis occurrence was high in ICU patients with heroin and amphetamine intoxication. Therefore, clinicians should anticipate this complication, monitor for rhabdomyolysis, and institute appropriate treatment protocols early in the patient's clinical course.
Topics: Humans; Heroin; Incidence; Creatinine; Rhabdomyolysis; Central Nervous System Agents
PubMed: 37848606
DOI: 10.1038/s41598-023-45031-4 -
The Australian and New Zealand Journal... Feb 2024Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is... (Review)
Review
OBJECTIVE
Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies.
METHODS
A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality.
RESULTS
A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%.
CONCLUSION
Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.
Topics: Humans; Alcoholism; Acamprosate; Cost-Benefit Analysis; Naltrexone; Alcohol Drinking; Ethanol
PubMed: 37822267
DOI: 10.1177/00048674231201541 -
European Addiction Research 2023The phenomenon of craving and attention bias towards drug cues is theorized to operate cooperatively, owing to the principles of associative learning. In this context,...
INTRODUCTION
The phenomenon of craving and attention bias towards drug cues is theorized to operate cooperatively, owing to the principles of associative learning. In this context, the conditioned response to drug-related stimuli activates reward mechanisms within the brain, consequently inducing craving and fostering the underlying mechanisms that contribute to relapse in individuals with substance use disorders. Multiple studies have assessed the relationship between attention to substance-related cues and subjective craving through electroencephalography (EEG), but their findings have yet to be synthesized and examined. This review summarizes the association between the amplitude of the P300 event-related potential (ERP) and substance use craving, compares discrepancies in results by type of substance, and discusses gaps in the literature to inform future research.
METHODS
A systematic search was conducted on Embase, Web of Science, CINAHL, and PsychINFO databases. Studies were published in English and included peer-reviewed human research investigating the relationship between EEG P300 ERP and self-reported substance use craving. The included study samples comprised of in treatment or non-treatment-seeking participants who use substances. The primary outcomes of interest were those derived from inferential statistics assessing P300 amplitude and substance use craving.
RESULTS
Ten studies were included in the final search and were organized by substance type: three alcohol, three cocaine, two tobacco, one heroin, and one cannabis. Results were mixed for alcohol and cocaine. Studies on tobacco, heroin, and cannabis use were congruent for associations between the P300 amplitude and craving.
CONCLUSIONS
Overall findings are mixed between studies addressing the association of the EEG P300 amplitude and craving. These results should be considered in the context of the limited sample size, underpowered analyses, and methodological differences that potentially contribute to discrepancies in outcomes. Further research is required to assess the role of craving assessment, EEG methodology, and substance-related factors on the association between P300 amplitude and self-reported craving.
Topics: Humans; Craving; Event-Related Potentials, P300; Self Report; Heroin; Substance-Related Disorders; Cocaine; Ethanol; Cues
PubMed: 37820586
DOI: 10.1159/000533147 -
Scandinavian Journal of Pain Jan 2024Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been... (Meta-Analysis)
Meta-Analysis
High-frequency, high-intensity transcutaneous electrical nerve stimulation compared with opioids for pain relief after gynecological surgery: a systematic review and meta-analysis.
OBJECTIVES
Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been used for acute pain treatment and has dose-dependent analgesic effects, and therefore presents an alternative to intravenous (iv) opioids for postoperative pain relief. The aim of this meta-analysis was to compare high-frequency, high-intensity (HFHI or intense) TENS to iv opioids with regard to postoperative pain intensity, recovery time in the Post Anesthesia Care Unit (PACU) and opioid consumption after elective gynecological surgery.
METHODS
We searched Medline, Embase, Web of Science, Cochrane, Amed and Cinahl for RCTs and quasi-experimental studies (2010-2022), and WHO and ClinicalTrials.gov for ongoing/unpublished studies. Meta-analysis and subsequent Trial Sequential Analysis (TSA) was performed for all stated outcomes. Quality of evidence was assessed according to GRADE.
RESULTS
Only three RCTs met the inclusion criteria (362 participants). The surgical procedures involved surgical abortion, gynecologic laparoscopy and hysteroscopy. The applied TENS frequency was 80 Hz and intensity 40-60 mA. There was no difference in pain intensity according to Visual Analogue Scale (VAS) at discharge from PACU between the TENS and opioid group (MD VAS -0.15, 95 % CI -0.38 to 0.09) (moderate level of evidence). Time in PACU was significantly shorter in the TENS group (MD -15.2, 95 % -22.75 to -7.67), and this finding was manifested by TSA (high-level of evidence). Opioid consumption in PACU was lower in the TENS group (MD Morphine equivalents per patient mg -3.42, 95 % -4.67 to -2.17) (high-level of evidence).
CONCLUSIONS
There was no detectable difference in postoperative pain relief between HFHI TENS and iv opioids after gynecological surgery. Moreover, HFHI TENS decreases recovery time and opioid consumption in PACU. HFHI TENS may be considered an opioid-sparing alternative for postoperative pain relief after gynecological surgery.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021231048.
Topics: Pregnancy; Female; Humans; Analgesics, Opioid; Transcutaneous Electric Nerve Stimulation; Gynecologic Surgical Procedures; Morphine; Pain, Postoperative
PubMed: 37819201
DOI: 10.1515/sjpain-2023-0068 -
Phytomedicine : International Journal... Dec 2023Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have... (Review)
Review
BACKGROUND
Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have been conducted to elucidate the pharmacological mechanisms of SIN in the treatment of RA. However, the molecular mechanism of SIN in RA has not been fully elucidated.
PURPOSE
To summarize the pharmacological effects and molecular mechanisms of SIN in RA and clarify the most valuable regulatory mechanisms of SIN to provide clues and a basis for basic research and clinical applications.
METHODS
We systematically searched SciFinder, Web of Science, PubMed, China National Knowledge Internet (CNKI), the Wanfang Databases, and the Chinese Scientific Journal Database (VIP). We organized our work based on the PRISMA statement and selected studies for review based on predefined selection criteria.
OUTCOME
After screening, we identified 201 relevant studies, including 88 clinical trials and 113 in vivo and in vitro studies on molecular mechanisms. Among these studies, we selected key results for reporting and analysis.
CONCLUSIONS
We found that most of the known pharmacological mechanisms of SIN are indirect effects on certain signaling pathways or proteins. SIN was manifested to reduce the release of inflammatory cytokines such as Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1β, thereby reducing the inflammatory response, and apparently blocking the destruction of bone and cartilage. The regulatory effects on inflammation and bone destruction make SIN a promising drug to treat RA. More notably, we believe that the modulation of α7nAChR and the regulation of methylation levels at specific GCG sites in the mPGES-1 promoter by SIN, and its mechanism of directly targeting GBP5, certainly enriches the possibilities and the underlying rationale for SIN in the treatment of inflammatory immune-related diseases.
Topics: Humans; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Morphinans; Signal Transduction
PubMed: 37816287
DOI: 10.1016/j.phymed.2023.155114 -
CNS Drugs Oct 2023A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as...
BACKGROUND
A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.
OBJECTIVES
The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.
METHODS
We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: "AXS-05" OR "dextromethorphan and bupropion" AND "depression". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.
RESULTS
The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.
CONCLUSION
Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.
Topics: Adult; Humans; Antidepressive Agents; Bupropion; Depression; Depressive Disorder, Major; Dextromethorphan; Clinical Trials as Topic
PubMed: 37792265
DOI: 10.1007/s40263-023-01032-5 -
British Journal of Anaesthesia Dec 2023Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of non-neuraxial analgesic techniques for midline laparotomy: a systematic review and frequentist network meta-analysis of randomised controlled trials.
BACKGROUND
Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events.
METHODS
We searched Ovid MEDLINE, Embase, Cochrane Central, and Scopus databases for studies comparing commonly used non-neuraxial analgesic techniques for midline laparotomy in adult patients. The co-primary outcomes of the study were 24-h cumulative opioid consumption and 24-h resting pain score, reported as i.v. morphine equivalents and 11-point numerical rating scale, respectively. We performed a frequentist meta-analysis using a random-effects model and a cluster-rank analysis of the co-primary outcomes.
RESULTS
Of 6115 studies screened, 67 eligible studies were included (n=4410). Interventions with the greatest reduction in 24-h cumulative opioid consumption compared with placebo/no intervention were single-injection quadratus lumborum block (sQLB; mean difference [MD] -16.1 mg, 95% confidence interval [CI] -29.9 to -2.3, very low certainty), continuous transversus abdominis plane block (cTAP; MD -14.0 mg, 95% CI -21.6 to -6.4, low certainty), single-injection transversus abdominis plane block (sTAP; MD -13.7 mg, 95% CI -17.4 to -10.0, low certainty), and continuous rectus sheath block (cRSB; MD -13.2 mg, 95% CI -20.3 to -6.1, low certainty). Interventions with the greatest reduction in 24-h resting pain score were cRSB (MD -1.2, 95% CI -1.8 to -0.6, low certainty), cTAP (MD -1.0, 95% CI -1.7 to -0.2, low certainty), and continuous wound infusion (cWI; MD -0.7, 95% CI -1.1 to -0.4, low certainty). Clustered-rank analysis including the co-primary outcomes showed cRSB and cTAP blocks to be the most efficacious interventions.
CONCLUSIONS
Based on current evidence, continuous rectus sheath block and continuous transversus abdominis plane block were the most efficacious non-neuraxial techniques at reducing 24-h cumulative opioid consumption and 24-h resting pain scores after midline laparotomy (low certainty). Future studies should compare techniques for upper vs lower midline laparotomy and other non-midline abdominal incisions.
CLINICAL TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021269044.
Topics: Adult; Humans; Analgesics, Opioid; Laparotomy; Network Meta-Analysis; Morphine; Pain; Pain, Postoperative
PubMed: 37770254
DOI: 10.1016/j.bja.2023.08.024