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Obesity Reviews : An Official Journal... Nov 2023This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed... (Review)
Review
Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies.
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for C-raclopride, F-fallypride, I-IBZM; one for dopamine transporter, I-FP-CIT; one used tracer for serotonin 5-HT receptor, F-altanserin; two used tracers for serotonin transporter, C-DASB or I-FP-CIT; two used tracer for μ-opioid receptor, C-carfentanil; one used tracer for noradrenaline transporter, C-MRB); seven studies assessed glucose uptake using F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using O-H O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using F-FTHA and one using C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
Topics: Humans; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Bariatric Surgery; Brain; Obesity; Neurotransmitter Agents
PubMed: 37699864
DOI: 10.1111/obr.13620 -
Schizophrenia Research. Cognition Dec 2023In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on...
BACKGROUND
In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT partial agonists in improving other domains of neurocognitive function in schizophrenia patients.
METHODS
A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis.
RESULTS
5-HT partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = -0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = -0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = -0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = -0.10, 95 % CI = -0.53 to 0.33).
CONCLUSIONS
The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.
PubMed: 37732133
DOI: 10.1016/j.scog.2023.100290 -
Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis.The Egyptian Heart Journal : (EHJ) :... Jul 2023Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for...
BACKGROUND
Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron.
METHODS
A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020).
RESULTS
A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18-50 years and among patients older than 50 years.
CONCLUSIONS
The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.
PubMed: 37395900
DOI: 10.1186/s43044-023-00385-y -
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 -
CNS & Neurological Disorders Drug... Jun 2024Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin... (Meta-Analysis)
Meta-Analysis
Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.
BACKGROUND
Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far.
METHODS
The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia).
RESULTS
The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan.
CONCLUSION
The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.
PubMed: 38847252
DOI: 10.2174/0118715273304677240529062909 -
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 -
European Journal of Surgical Oncology :... Jun 2024There has been a lack of research comparing the efficacy of various treatments for low anterior resection syndrome (LARS). (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There has been a lack of research comparing the efficacy of various treatments for low anterior resection syndrome (LARS).
METHODS
We conducted a comprehensive search across six electronic databases and a paired meta-analysis was undertaken to assess the effectiveness of the interventions. Furthermore, a network meta-analysis was utilized to compare the efficacy of different treatments for LARS.
RESULTS
This study encompassed nine randomized controlled trials, involving a total of 450 patients. Compared to routine care, 5-HT3 receptor antagonists (follow-up<3 months) and percutaneous tibial nerve stimulation (3 months ≤ follow-up <6 months) were effective in reducing the LARS score. Pelvic floor rehabilitation (follow-up≤3 months) was effective in decreasing daily number of bowel movements when compared to routine care. The network meta-analysis indicated that 5-HT3 receptor antagonists (follow-up<3 months) were the most effective in reducing both the LARS score and the daily number of bowel movements. Transanal irrigation (3 months ≤ follow-up ≤ 12 months) was most effective in reducing the LARS score. Additionally, 5-HT3 receptor antagonists demonstrated relative efficacy in improving patients' quality of life (follow-up ≤ 1 month).
CONCLUSIONS
This review indicates that 5-HT3 receptor antagonists and anal irrigation show significant promise in the treatment of LARS. Nevertheless, the contributions of percutaneous tibial nerve stimulation and pelvic floor rehabilitation to LARS treatment should not be overlooked. Given the clinical heterogeneity observed among the studies, the results should be interpreted with caution.
Topics: Humans; Network Meta-Analysis; Pelvic Floor; Postoperative Complications; Proctectomy; Randomized Controlled Trials as Topic; Rectal Neoplasms; Serotonin 5-HT3 Receptor Antagonists; Tibial Nerve; Transcutaneous Electric Nerve Stimulation
PubMed: 38626589
DOI: 10.1016/j.ejso.2024.108336 -
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 -
Asian Journal of Psychiatry May 2024Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD.... (Meta-Analysis)
Meta-Analysis Review
Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace.
METHODS
PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes.
RESULTS
A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo.
CONCLUSION
Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.
Topics: Humans; Randomized Controlled Trials as Topic; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Piperazines; Drug Therapy, Combination; Antidepressive Agents; Outcome Assessment, Health Care
PubMed: 38513509
DOI: 10.1016/j.ajp.2024.104005