-
Frontiers in Pharmacology 2023Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women...
Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women suffer from morning sickness, a condition characterized by nausea and vomiting. However, it is still controversial regarding its safety during pregnancy, and continued research will be necessary to fully understand the risks and benefits associated with its use. Therefore, we aimed to identify and provide details of the efficacy and safety of ondansetron in clinical trials. A search was conducted of the ClinicalTrials.gov database on 13 April 2023, using the search term "ondansetron and pregnancy." Inclusion and exclusion criteria were defined to identify relevant clinical trials. The inclusion criteria encompassed clinical trials related to pregnancy that utilized ondansetron as a treatment, while other clinical trials were excluded from consideration. All data extractions such as study title, study status, study type, intervention details, and outcome were collected. A total of 18 clinical trials were identified, of which only 6 focused on studying the effects of ondansetron. Their respective study titles, statuses, conditions, interventions, outcome measures, and enrollment sizes have been written in detail. The information collected from these trials will contribute to our understanding of the potential benefits and risks of ondansetron in the context of pregnancy and its complications. Ondansetron has been shown to be an effective treatment for nausea and vomiting, including pregnancy-related morning sickness. Further research is needed to better understand the potential risks and benefits associated with its use in pregnant women. ClinicalTrials.gov, identifier.
PubMed: 37936910
DOI: 10.3389/fphar.2023.1291235 -
Diseases (Basel, Switzerland) Dec 2022There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin...
There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81-3.50, 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27-2.96, 96.46%), NSAIDs (OR 2.02, 95% CI 1.33-2.70, 92.70%) and Statins (OR 1.74, 95% CI 1.19-2.30, 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32-5.08, 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90-6.19, 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54-4.92, 98.31%), NSAIDs (OR 3.27, 95% CI 2.06-4.48, 95.38%), and Statins (OR 2.23, 95% CI 1.41-3.06, 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48-0.88, 7.26%), (OR 0.46, 95% CI 0.14-0.78, 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49-1.42, 37.89%), NSAIDs (OR 1.13, 95% CI 0.49-1.76, 59.37%) Statins (OR 0.91, 95% 0.66-1.17, 0%) and H2RA (OR 3.48, 95% CI -0.41-7.36, 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50-1.72, 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group.
PubMed: 36648871
DOI: 10.3390/diseases11010006 -
BMC Medicine Dec 2016Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.
RESULTS
After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.
CONCLUSIONS
Most 5-HT receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.
TRIAL REGISTRATION
This study was registered at PROSPERO: ( CRD42013003564 ).
Topics: Adult; Antiemetics; Antineoplastic Agents; Drug Therapy, Combination; Glucocorticoids; Humans; Nausea; Network Meta-Analysis; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 28007031
DOI: 10.1186/s12916-016-0761-9 -
The Cochrane Database of Systematic... Mar 2017Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children.
OBJECTIVES
To determine the effectiveness of pharmacological interventions for RAP in children of school age.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies.
SELECTION CRITERIA
Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results.
MAIN RESULTS
This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies.
AUTHORS' CONCLUSIONS
There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.
Topics: Abdominal Pain; Adolescent; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome
PubMed: 28262913
DOI: 10.1002/14651858.CD010973.pub2 -
Neuroscience and Biobehavioral Reviews Aug 2022The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain... (Review)
Review
The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain information about personal experiences, general facts, and events. Several psychiatric or neurological diseases, such as depression, attention-deficit-hyperactivity disorder (ADHD), and dementia, show alterations in serotonergic signalling and attendant memory disorders. Nevertheless, understanding serotonergic neurotransmission and its influence on memory remained a challenge until today. In this systematic review, we summarize recent psychopharmacological studies in animals and humans from a psychological memory perspective, in consideration of task-specific requirements. This approach has the advantage that comparisons between serotonin (5-HT)-related neurochemical mechanisms and manipulations are each addressing specific mnemonic circuits. We conclude that applications of the same 5-HT-related treatments can differentially affect unrelated tasks of declarative memories. Moreover, the analysis of specific mnemonic phases (e.g., encoding vs. consolidation) reveals opposing impacts of increased or decreased 5-HT tones, with low 5-HT supporting spatial encoding but impairing the consolidation of objects and verbal memories. Promising targets for protein synthesis-dependent consolidation enhancements include 5-HT receptor agonists and 5-HT receptor antagonists, with the latter being of special interest for the treatment of age-related decline. Further implications are pointed out as base for the development of novel therapeutic targets for memory impairment of neuropsychiatric disorders.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Humans; Memory; Memory Disorders; Serotonin
PubMed: 35691469
DOI: 10.1016/j.neubiorev.2022.104729 -
Neuroscience and Biobehavioral Reviews Dec 2016Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as... (Review)
Review
Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: "ayahuasca", "DMT", "psilocybin", "LSD", "mescaline" crossed one by one with the terms "mri", "fmri", "pet", "spect", "imaging" and "neuroimaging". Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.
Topics: Cerebral Cortex; Hallucinogens; Humans; Male; Neuroimaging; Psilocybin; Receptor, Serotonin, 5-HT2A
PubMed: 27810345
DOI: 10.1016/j.neubiorev.2016.10.026 -
Indian Pediatrics Aug 2023Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with...
BACKGROUND
Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with migraines. Even though triptans are often used to treat acute migraines, there is some debate over their effectiveness.
OBJECTIVE
Our systematic review aimed to evaluate the effectiveness of triptans for acute treatment of migraine in young individuals.
METHODS
Utilizing the databases of Google Scholar, Cochrane Library, and PubMed, a literature search was conducted, and all papers published till July 2022 were included. This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. In addition to the Boolean operators AND, OR, and NOT, the following descriptive terms were also used: "Triptans," "Pediatric Migraine," "Migraine disorders," "Headache," "Children," and "Adolescent."
RESULTS
A total of 1047 studies were identified, and 25 articles were finally included in the study. 17 of them were RCTs while the remaining were non-randomized trials. Most studies recruited participants aged between 12-17 years. Among 25 studies, 7 reported sumatriptan use, 3 assessed a combination of sumatriptan and naproxen, 4 were on almotriptan, 1 on eletriptan, 6 on rizatriptan, and 4 on zolmitriptan use.
CONCLUSION
We found that rizatriptan (good tolerability profile with a dose of 5 mg) and sumatriptan (nasal spray, 10 mg and 20 mg) had higher efficiency as compared to other triptans. Regardless of type or dose, all triptans are generally well tolerated by patients, but a few adverse effects such as light-headedness (sumatriptan), nasopharyngitis, and, muscular spasms (sumatriptan/ naproxen), somnolence, and dry mouth (rizatriptan), and dizziness (zolmitriptan group) were reported with the triptans.
Topics: Adolescent; Humans; Child; Sumatriptan; Naproxen; Tryptamines; Migraine Disorders; Headache
PubMed: 37209053
DOI: No ID Found -
Pharmacology, Biochemistry, and Behavior Feb 2023Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are... (Review)
Review
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Topics: Humans; Ketamine; Depression; Depressive Disorder, Major; Systems Biology; Antidepressive Agents; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 36731751
DOI: 10.1016/j.pbb.2023.173523 -
BMC Medicine Jun 2015Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic review on the comparative safety 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 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, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles. Significantly more patients receiving granisetron plus dexamethasone experienced an arrhythmia relative to placebo (odds ratio (OR) 2.96, 95 % confidence interval (CI) 1.11-7.94), ondansetron (OR 3.23, 95 % CI 1.17-8.95), dolasetron (OR 4.37, 95 % CI 1.51-12.62), tropisetron (OR 3.27, 95 % CI 1.02-10.43), and ondansetron plus dexamethasone (OR 5.75, 95 % CI 1.71-19.34) in a NMA including 31 randomized clinical trials (RCTs) and 6,623 patients of all ages. No statistically significant differences in delirium frequency were observed across all treatment comparisons in a NMA including 18 RCTs and 3,652 patients.
CONCLUSION
Granisetron plus dexamethasone increases the risk of arrhythmia.
Topics: Antiemetics; Humans; Postoperative Nausea and Vomiting; Registries; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 26084332
DOI: 10.1186/s12916-015-0379-3 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159