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Scientific Reports Jun 2024There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.
There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes.
Topics: Fluvoxamine; Humans; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Treatment Outcome; Clinical Deterioration; Selective Serotonin Reuptake Inhibitors
PubMed: 38862591
DOI: 10.1038/s41598-024-64260-9 -
Journal of Gastrointestinal and Liver... Jun 2020Multiple pharmacologic treatments are available for the management of irritable bowel syndrome (IBS), and a large body of evidence has been presented. However, the...
BACKGROUND AND AIMS
Multiple pharmacologic treatments are available for the management of irritable bowel syndrome (IBS), and a large body of evidence has been presented. However, the strength and credibility of the evidence have not been comprehensively evaluated. We aimed to review the systematic reviews and meta- analyses of pharmacologic treatments for IBS and evaluate the credibility of the findings.
METHODS
We searched MEDLINE, Embase, and Cochrane library from inception to September 2019 for systematic reviews evaluating the effectiveness of pharmacologic treatments for IBS. We summarized relative ratios (RR), evaluated the credibility of the evidence and classified the evidence into convincing, highly suggestive, suggestive, and weak.
RESULTS
We included 11 systematic reviews with 40 meta-analyses (330 randomized controlled trials and 86,459 participants) assessing 10 treatment categories and 2 drugs. Most of the pharmacologic treatments were significantly superior over placebo as reported by the included meta-analyses. The evidence for 5-hydroxytryptamine (5-HT)3 antagonists (RR=1.56, 95%CI: 1.43-1.71), antispasmodics (RR=1.19, 95%CI: 1.02-1.39), and alosetron (RR=1.46, 95%CI: 1.26-1.71) were highly suggestive for relieving global IBS symptoms. 5-HT4 agonists (RR= 1.26, 95%CI: 1.19-1.34) and guanylate cyclase-C (GCC) agonists (RR=1.73, 95%CI: 1.54-1.95) were found to give convincing evidence for the improvement of the responder rate. 5-HT3 antagonists (RR=1.32, 95%CI: 1.26-1.38) offered convincing evidence for relieving abdominal pain.
CONCLUSIONS
Evidence for 5-HT3 antagonists, 5-HT4 agonists and GCC agonists, antispasmodics, and alosetron were suggestive for the treatment of IBS. However, owing to the risk of bias in randomization methods, the results for GCC should be interpreted with caution.
Topics: Carbolines; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Humans; Irritable Bowel Syndrome; Parasympatholytics; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome
PubMed: 32530987
DOI: 10.15403/jgld-817 -
The Journal of Headache and Pain Jun 2020Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT) receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT) receptor agonist, appears more promising for the acute treatment of migraine because of considerably better effect profiles with no severe adverse events (AEs). This review aimed to systematically evaluate the efficacy and safety of lasmiditan from the results of randomized controlled trials (RCTs).
METHODS
PubMed, Cochrane Library, Embase were searched on lasmiditan for the acute treatment of migraine from inception of the databases to Feb 1, 2020. Pain free and pain relief, global impression (very much/much better), and no/mild disability at 2 h in efficacy; total treatment-emergent adverse events (TEAEs), dizziness, nausea, fatigue, paraesthesia and somnolence in safety were extracted from the included studies. A systematic review and meta-analysis was performed using Review Manager Software version 5.3 (RevMan 5.3).
RESULTS
Four RCTs with a total of 4960 subjects met our inclusion criteria. The overall effect estimate showed that lasmiditan was significantly superior to placebo in terms of pain free (RR 1.71, 95% CI 1.55-1.87), pain relief (RR 1.40, 95% CI 1.33-1.47), global impression (very much/much better) (RR 1.55, 95% CI 1.44-1.67), and no/mild disability (RR 1.15, 95% CI 1.10-1.20) at 2 h. For the safety, significant number of patients experienced TEAEs with lasmiditan than with placebo (RR 2.77, 95% CI 2.53-3.03), most TEAEs were central nervous system (CNS)-related and included dizziness (RR 5.81, 95% CI 4.72-7.14), nausea (RR 2.58, 95% CI 1.87-3.57), fatigue (RR 5.38, 95% CI 3.78-7.66), paraesthesia (RR 4.48, 95% CI 3.33-6.02), and somnolence (RR 2.82, 95% CI 2.18-3.66).
CONCLUSIONS
This meta-analysis suggests that lasmiditan is effective for the acute treatment of migraine with a higher incidence of CNS-related adverse reactions compared with placebo. Long-term, open-label, multi-dose trials are required to verify the current findings.
Topics: Benzamides; Dizziness; Humans; Migraine Disorders; Nausea; Piperidines; Pyridines; Receptors, Serotonin; Serotonin Receptor Agonists; Time Factors; Treatment Outcome; Vertigo; Receptor, Serotonin, 5-HT1F
PubMed: 32503415
DOI: 10.1186/s10194-020-01138-x -
ESMO Open Feb 2020We performed a pooled analysis to evaluate the efficacy and adverse events (AEs) of olanzapine combined with dexamethasone plus 5-hydroxytryptamine type 3 receptor... (Meta-Analysis)
Meta-Analysis
Olanzapine combined with 5-hydroxytryptamine type 3 receptor antagonist (5-HT3 RA) plus dexamethasone for prevention and treatment of chemotherapy-induced nausea and vomiting in high and moderate emetogenic chemotherapy: a systematic review and meta-analysis of randomised controlled trials.
We performed a pooled analysis to evaluate the efficacy and adverse events (AEs) of olanzapine combined with dexamethasone plus 5-hydroxytryptamine type 3 receptor antagonist (5-HT3 RA) compared with 5-HT3 RA plus dexamethasone for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in high and moderate emetogenic chemotherapy based on randomised controlled trials (RCTs). PubMed, EMBASE, Web of Science, the Cochrane Library, China Biomedical Literature database (CBM), WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP) (from their inception to April 2019) were searched to capture relevant articles. Relative risk with 95% confidence intervals for CINV and AEs were all extracted or calculated. Eleven studies with 1107 cancer patients were involved in this review. The pooled RR of delayed CINV (RR 0.50, 95% CI 0.38 to 0.66; p<0.01) were significantly decreased in the olanzapine group. The occurrence of insomnia was also statistically decreased, as was the rate of acute CINV (RR 0.60, 95% CI 0.48 to 0.75; p<0.01). However, only the percentages of CINV III and CINV IV were significantly decreased in the acute and delayed phases. Subgroup analysis demonstrated that the efficacy was not statistically significantly different between 5 mg and 10 mg olanzapine. Olanzapine significantly decreased the occurrence of CINV III and IV and insomnia in high and moderately emetogenic chemotherapy. Compared with 10 mg per day, 5 mg oral olanzapine may be more appropriate for patients with cancer.
Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Humans; Nausea; Olanzapine; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 32079622
DOI: 10.1136/esmoopen-2019-000621 -
BMJ Open Oct 2020Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT receptor... (Meta-Analysis)
Meta-Analysis
5-HT receptor antagonists for the prevention of perioperative shivering undergoing spinal anaesthesia: a systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT receptor antagonists in preventing POS following spinal anaesthesia.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Pubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019.
ELIGIBILITY CRITERIA
Randomised controlled trials that reported the effects of 5-HT receptor antagonists in the prevention of POS in patients after spinal anaesthesia.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated.
RESULTS
A total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p<0.01; I=0%). Subgroup analysis for different types of 5-HT receptor antagonists and timing of administration produced similar results. Also, patients had a lower incidence of postoperative nausea and vomiting after administrating 5-HT3 receptor antagonists. No statistically significant differences in drug-related adverse effects were observed. Grading of Recommendations Assessment, Development and Evaluation revealed a high level of evidence. The cumulative z-curve crossed the trial sequential monitoring boundary.
CONCLUSIONS
The present study revealed that prophylactic 5-HT receptor antagonists were an effective measure for reducing the incidence of POS in patients after spinal anaesthesia. However, further studies investigating the different types of surgeries are required.
PROSPERO REGISTRATION NUMBER
CRD42019148191.
Topics: Anesthesia, Spinal; Humans; Pharmaceutical Preparations; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Serotonin; Shivering
PubMed: 33020100
DOI: 10.1136/bmjopen-2020-038293 -
The American Surgeon Jun 2024Prolonged postoperative ileus (PPOI) contributes to morbidity and prolonged hospitalization. Prucalopride, a selective 5-hydroxytryptamine receptor agonist, may enhance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prolonged postoperative ileus (PPOI) contributes to morbidity and prolonged hospitalization. Prucalopride, a selective 5-hydroxytryptamine receptor agonist, may enhance bowel motility. This review assesses whether the perioperative use of prucalopride compared to placebo is associated with accelerated return of bowel function post gastrointestinal (GI) surgery.
METHODS
OVID, CENTRAL, and EMBASE were searched as of January 2024 to identify randomized controlled trials (RCTs) comparing prucalopride and placebo for prevention of PPOI in adult patients undergoing GI surgery. The primary outcomes were time to stool, time to flatus, and time to oral tolerance. The secondary outcomes were incidence of PPOI, length of stay (LOS), postoperative complications, adverse events, and overall costs. The Cochrane risk of bias tool for randomized trials and the Grading of Recommendations, Assessment, Development, and Evaluations framework were used. An inverse variance random effects model was used.
RESULTS
From 174 citations, 3 RCTs with 139 patients in each treatment group were included. Patients underwent a variety of GI surgeries. Patients treated with prucalopride had a decreased time to stool (mean difference 36.82 hours, 95% CI 59.4 to 14.24 hours lower, I = 62%, low certainty evidence). Other outcomes were not statistically significantly different (very low certainty evidence). Postoperative complications and adverse events could not be meta-analyzed due to heterogeneity; yet individual studies suggested no significant differences (very low certainty evidence).
DISCUSSION
Current RCT evidence suggests that prucalopride may enhance postoperative return of bowel function. Larger RCTs assessing patient important outcomes and associated costs are needed before routine use of this agent.
Topics: Humans; Benzofurans; Digestive System Surgical Procedures; Gastrointestinal Motility; Ileus; Length of Stay; Postoperative Complications; Randomized Controlled Trials as Topic; Serotonin 5-HT4 Receptor Agonists
PubMed: 38530772
DOI: 10.1177/00031348241241683 -
Clinical Psychopharmacology and... Feb 2024Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research... (Review)
Review
Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research into this compound is scarce with few FDA-approved clinical studies. Despite this, profound findings into its antidepressant effects (largely through its action on 5-HT1a receptors) in mental illnesses such as major depressive disorder have rapidly increased interest back into their potential therapeutic benefits. This systematic review provides an analysis of the studies examining the clinical use of psilocybin for major depressive disorder. In total 6 studies were selected, including 319 participants, with half being randomised controlled trials and half open label trials. In every study psychological support was included as an integral part of the treatment. It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects. This gives psilocybin an advantage over commonly prescribed selective serotonin reuptake inhibitors (SSRIs), which carry more risk and cause more adverse effects. This drug therefore shows promise for being used as a clinical treatment for major depressive disorder, however future research should develop a paradigm for its use, with the timing of sessions and type of psychological support specified to allow for more precise analysis of the clinical effects of the drug. Additionally, more studies into its clinical efficacy are needed for appropriate detection of any publication bias. With this, psilocybin could prove to be revolutionary in treating depression and become an alternative medication to SSRIs.
PubMed: 38247407
DOI: 10.9758/cpn.23.1120 -
Molecular Pain 2021Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions...
Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions for neuropathic pain often fail, insights into the underlying mechanism and role of identified receptors is of utmost importance. An important target for improving treatment of neuropathic pain is the descending serotonergic system as these projections modulate nociceptive signaling in the dorsal horn. Also with use of last resort treatments like spinal cord stimulation (SCS), the descending serotonergic projections are known to be involved in the pain relieving effect. This systematic review summarizes the involvement of the serotonergic system on nociceptive modulation in the healthy adult rodent and the chronic neuropathic rodent and summarizes all available literature on the serotonergic system in the SCS-treated neuropathic rodent. Medline, Embase and Pubmed databases were used in the search for articles. Descending serotonergic modulation of nociceptive signaling in spinal dorsal horn in normal adult rat is mainly inhibitory and mediated by 5-HT1a, 5-HT1b, 5-HT2c, 5-HT3 and 5-HT4 receptors. Upon injury and in the neuropathic rat, this descending serotonergic modulation becomes facilitatory via activation of the 5-HT2a, 5-HT2b and 5-HT3 receptors. Analgesia due to neuromodulatory intervention like SCS restores the inhibitory function of the descending serotonergic system and involves 5-HT2, 5-HT3 and 5-HT4 receptors. The results of this systematic review provide insights and suggestions for further pharmacological and or neuromodulatory treatment of neuropathic pain based on targeting selected serotonergic receptors related to descending modulation of nociceptive signaling in spinal dorsal horn. With the novel developed SCS paradigms, the descending serotonergic system will be an important target for mechanism-based stimulation induced analgesia.
Topics: Animals; Humans; Neuralgia; Nociception; Rats; Receptors, Serotonin, 5-HT3; Spinal Cord; Spinal Cord Dorsal Horn; Spinal Cord Stimulation
PubMed: 34662215
DOI: 10.1177/17448069211043965 -
Frontiers in Psychiatry 2020Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be...
Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies.
PubMed: 32256403
DOI: 10.3389/fpsyt.2020.00172 -
Eating and Weight Disorders : EWD Oct 2019To evaluate and understand the genetic and epigenetic basis of bulimia nervosa/bulimia spectrum disorder and comorbid borderline personality disorder (BN/BSD-BPD).
PURPOSE
To evaluate and understand the genetic and epigenetic basis of bulimia nervosa/bulimia spectrum disorder and comorbid borderline personality disorder (BN/BSD-BPD).
METHODS
The present systematic review was conducted in accordance to PRISMA guidelines. Advanced systematic searches of Medline, EMBASE, PsychINFO, Web of Science, Scopus, CINHAL plus, and the Cochrane Library were conducted using the search terms 'bulimia nervosa', 'bulimia spectrum disorder', 'borderline personality disorder', 'genes', and 'genetics'. The search strategy garnered seven studies for inclusion in the present review.
RESULTS
Women with BN/BSD-BPD had significantly lower serotonin and monoamine oxidise activity compared to women with BN/BSD or healthy controls (HC). As well, women with BN/BSD-BPD displayed elevated methylation of the dopamine receptor gene promoter, brain-derived neurotrophic factor, and changes in the methylation of the glucocorticoid receptor gene promoter (NR3C1) compared to women with BN/BSD and HC. The results also demonstrated that rates of childhood sexual abuse and childhood physical abuse are higher in those with BN/BSD-BPD than those with BN/BSD and HC, and that these types of abuse are often correlated with the methylation differences seen in BN/BSD-BPD women.
CONCLUSION
Due to the differences observed between individuals with BN/BSD-BPD and those with BN/BSD and HC a genetic/epigenetic aetiological model of BN/BSD-BPD was developed and is proposed in this review. This evidence-based model visually illustrates the current state of the field and draws attention to the need for subsequent research.
Topics: Adult Survivors of Child Abuse; Borderline Personality Disorder; Bulimia; Bulimia Nervosa; Epigenesis, Genetic; Humans
PubMed: 31119586
DOI: 10.1007/s40519-019-00688-7