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BMC Medicine Jun 2015Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative efficacy of 5-HT3 receptor antagonists.
METHODS
Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 receptor antagonists with each other, placebo, and/or combined with other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564.
RESULTS
Overall, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients.
CONCLUSIONS
Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine.
Topics: Antiemetics; Humans; Postoperative Nausea and Vomiting; Registries; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 26084277
DOI: 10.1186/s12916-015-0371-y -
Biological Research For Nursing Jan 2015Coping refers to the way that an individual manages stress. Coping strategies vary; for example, problem-focused coping is directed at reducing or removing a stressor,... (Review)
Review
Coping refers to the way that an individual manages stress. Coping strategies vary; for example, problem-focused coping is directed at reducing or removing a stressor, while emotion-focused coping is directed more at managing reactions that accompany the stressor. How individuals cope with stress can impact their health, but the physiological effects of coping are not well understood. The field of genetics provides tools that could help illuminate the physiology of coping. This review of the literature was conducted to determine what is currently known about the phenotype of coping from a genetic perspective. PubMed, HubMed, PsychInfo, Medline, Scopus, and Google Scholar databases were used to conduct the search, and reference lists were reviewed to identify additional publications. Only studies that measured coping style or a coping domain specifically, were written in English language, and were human-subject focused were included in the review. We identified 19 studies that met these criteria, and 2 types of genetic studies emerged for the review: heritability (n = 9) and candidate gene association (n = 10) studies. Heritability estimates of .68-.76 support a nonadditive genetic component to coping. Replication of association was found for the serotonin transporter and adrenergic receptor beta 2 genes. In addition to finding evidence supporting a role for genetic variability with coping phenotype, it is worth noting that the review revealed a lack of consistency in instruments used to phenotype coping across studies.
Topics: Adaptation, Psychological; Humans; Stress, Psychological
PubMed: 25504954
DOI: 10.1177/1099800414527340 -
Journal of Psychopharmacology (Oxford,... Nov 2023Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies.
METHODS
Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted.
RESULTS
We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D receptor availability ( = 0.06, = 0.620), or combined dopamine synthesis and release capacity ( = 0.19, = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( = -0.56, = 0.006), but not when tracers with an affinity for serotonin transporters were included ( = -0.21, = 0.420). Subgroup analysis showed greater dopamine release ( = 0.49, = 0.030), but no difference in dopamine synthesis capacity ( = -0.21, = 0.434) in the MDD group. Striatal D receptor availability was lower in patients with MDD in two studies.
CONCLUSIONS
The meta-analysis indicates striatal DAT availability is lower, but D receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.
Topics: Humans; Dopamine; Depressive Disorder, Major; Tomography, Emission-Computed, Single-Photon; Positron-Emission Tomography; Receptors, Dopamine D2; Dopamine Plasma Membrane Transport Proteins
PubMed: 37811803
DOI: 10.1177/02698811231200881 -
Annals of Palliative Medicine Apr 2018Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's... (Comparative Study)
Comparative Study Review
Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments.
METHODS
A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases.
RESULTS
A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting.
CONCLUSIONS
The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.
Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Dexamethasone; Drug Combinations; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Radiotherapy; Randomized Controlled Trials as Topic; Serotonin Antagonists; Vomiting
PubMed: 29764184
DOI: 10.21037/apm.2018.03.09 -
Nutrients Jun 2023Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered... (Meta-Analysis)
Meta-Analysis Review
The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome.
Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered intestinal tryptophan metabolism in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls. Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites. Integration of the transcriptome and metabolome identified various alterations in intestinal tryptophan metabolism during active disease in IBD patients, including decreased intestinal tryptophan absorption, enhanced kynurenine pathway, increased interstitial serotonin availability, changed indole pathway, and activated aryl hydrocarbon receptor signaling. Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.
Topics: Humans; Tryptophan; Transcriptome; Inflammatory Bowel Diseases; Intestines; Metabolome
PubMed: 37447212
DOI: 10.3390/nu15132886 -
BMC Pharmacology & Toxicology Jan 2015Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists... (Review)
Review
BACKGROUND
Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists are effective antiemetics, yet may cause adverse cardiac events, such as arrhythmia. We aimed to identify interventions that mitigate the cardiac risk of 5-HT3 receptor antagonists.
METHODS
Electronic databases, trial registries, and references were searched. Studies on patients undergoing chemotherapy or surgery examining interventions to monitor cardiac risk of 5-HT3 receptor antagonists were included. Search results were screened and data from relevant studies were abstracted in duplicate. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) group's risk-of-bias tool. Due to a dearth of included studies, meta-analysis was not conducted.
RESULTS
Two randomized clinical trials (RCT) and 1 non-randomized clinical trial (NRCT) were included after screening 7,637 titles and abstracts and 1,554 full-text articles. Intravenous administration of different dolasetron doses was examined in the NRCT, while dolasetron versus ondansetron and palonosetron versus ondansetron were examined in the RCT. Electrocardiogram (ECG) was the only intervention examined to mitigate cardiac harm. No differences in ECG evaluations were observed between dolasetron or palonosetron versus ondansetron after 15 minutes, 24 hours, and 1 week post-administration in the 2 RCTs. Four deaths were observed in one RCT, which were deemed unrelated to palonosetron or ondansetron administration. Minor increases in PR and QT intervals were observed in the NRCT for dolasetron dosages greater than 1.2 mg/kg 1-2 hours post-administration, but were deemed not clinically relevant.
CONCLUSIONS
ECG monitoring of chemotherapy patients administered with 5-HT3 receptor antagonists did not reveal clinically significant differences in arrhythmia between the medications at the examined time periods. The usefulness of ECG to monitor chemotherapy patients administered with 5-HT3 receptor antagonists remains unclear, as all patients received ECG monitoring.
TRIAL REGISTRATION
PROSPERO registry number: CRD42013003565.
Topics: Antiemetics; Antineoplastic Agents; Arrhythmias, Cardiac; Drug Therapy, Combination; Electrocardiography; Humans; Indoles; Isoquinolines; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists
PubMed: 25623303
DOI: 10.1186/2050-6511-16-1 -
Current Neuropharmacology 2017Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at... (Review)
Review
BACKGROUND
Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment.
METHODS
We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel.
RESULTS
SNPs in 22 human genes have been linked to PTSD. These genes encode proteins acting as neurotransmitters and receptors, downstream signal transducers and metabolizing enzymes. Pharmacological inhibitors may serve as drug candidates for PTSD treatment, e.g. β2 adrenoreceptor antagonists, dopamine antagonists, partial dopamine D2 receptor agonists, dopamine β hydroxylase inhibitors, fatty acid amid hydrolase antagonists, glucocorticoid receptor agonists, tropomyosin receptor kinase B agonists, selective serotonin reuptake inhibitors, catechol-O-methyltransferase inhibitors, gamma-amino butyric acid receptor agonists, glutamate receptor inhibitors, monoaminoxidase B inhibitors, N-methyl-d-aspartate receptor antagonists.
CONCLUSION
The combination of genetic and pharmacological research may lead to novel targetbased drug developments with improved specificity and efficacy to treat PTSD. Specific SNPs may be identified as reliable biomarkers to assess individual disease risk. Focusing on soldiers suffering from PTSD will not only help to improve treatment options for this specific group, but for all PTSD patients and the general population.
Topics: Animals; Clinical Trials as Topic; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Military Personnel; Stress Disorders, Post-Traumatic
PubMed: 27834145
DOI: 10.2174/1570159X15666161111113514 -
PloS One 2017We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or... (Meta-Analysis)
Meta-Analysis Review
AIM
We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D).
METHODS
We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software.
RESULTS
We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43-1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26-1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98-4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]).
CONCLUSIONS
Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.
Topics: Humans; Irritable Bowel Syndrome; Placebos; Serotonin 5-HT3 Receptor Antagonists
PubMed: 28291778
DOI: 10.1371/journal.pone.0172846 -
The International Journal of... Dec 2022Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.
METHODS
We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.
RESULTS
Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.
CONCLUSIONS
Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Piperazines; Sulfides; Randomized Controlled Trials as Topic; Cognitive Dysfunction; Treatment Outcome; Double-Blind Method
PubMed: 35981958
DOI: 10.1093/ijnp/pyac054 -
Neuromuscular Disorders : NMD Dec 2020Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with...
Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with other syndromes that have a clear genetic background, in particular RYR1-related malignant hyperthermia. Through a literature review, performed according to the PRISMA guidelines, we aimed to report the clinical features of both syndromes, and the results of genetic testing performed. 10 case series and 99 case reports were included, comprising 134 patients. A male predominance of 58% was found. The median age was 35 (range 4-84) years. Eight patients experienced recurrent episodes of rhabdomyolysis. Genetic analysis was performed in eleven patients (8%), revealing four RYR1 variants, three likely benign (p.Asp849Asn, p.Arg4645Gln, p.Arg4645Gln) and one variant of uncertain significance (p.Ala612Thr). This review underlines that a subset of patients with neuroleptic malignant syndrome and serotonin syndrome develop recurrent episodes of rhabdomyolysis. This recurrent pattern suggests a possible underlying (genetic) susceptibility. However, the genetic background of neuroleptic malignant syndrome and serotonin syndrome has only been investigated to a very limited degree so far. The increasing availability of next generation sequencing offers an opportunity to identify potentially associated genetic backgrounds, especially in patients with recurrent episodes or a positive family history.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Malignant Hyperthermia; Middle Aged; Mutation; Neuroleptic Malignant Syndrome; Phenotype; Rhabdomyolysis; Ryanodine Receptor Calcium Release Channel; Serotonin Syndrome; Young Adult
PubMed: 33250373
DOI: 10.1016/j.nmd.2020.10.010