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Therapeutic Advances in... 2021Many older adults experience a deterioration in cognitive function with aging, and this can have a negative impact on quality of life. Late-life depression has been... (Review)
Review
Many older adults experience a deterioration in cognitive function with aging, and this can have a negative impact on quality of life. Late-life depression has been linked to mild cognitive impairment and dementia, and treating depression with an agent that has procognitive effects could be beneficial. Vortioxetine is a novel antidepressant with a multimodal mechanism of action that works primarily serotonin transporter inhibition, 5-HT receptor agonism and 5-HT receptor antagonism. A recent systematic review demonstrated procognitive effects of vortioxetine when indirectly compared with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in adults aged 18-65 years with major depressive disorder. While this systematic review demonstrated promising procognitive effects from vortioxetine, the included studies did not enroll older adults, who are at the highest risk of cognitive impairment. Therefore, our systematic review sought to investigate the effects of vortioxetine on cognitive functioning in patients over the age of 65 years. Three studies met the prespecified search criteria and were evaluated. Overall, these preliminary data suggest that vortioxetine has promising effects in improving cognition in older adults with depressive symptoms and may have a place in therapy in older adults with depression and/or cognitive impairment, including Alzheimer's disease. Additional long-term studies that include more diverse populations with comorbidities and direct comparisons with other antidepressants are needed to fully understand the potential cognitive benefits in older adults.
PubMed: 35186260
DOI: 10.1177/20451253211026796 -
Neuroscience and Biobehavioral Reviews Sep 2014Serotonergic dysfunction is thought to contribute to the pathophysiology of schizophrenia but the evidence has not been systematically synthesised before. We therefore... (Meta-Analysis)
Meta-Analysis Review
Serotonergic dysfunction is thought to contribute to the pathophysiology of schizophrenia but the evidence has not been systematically synthesised before. We therefore systematically reviewed postmortem and in vivo molecular imaging studies of serotonin function in schizophrenia. We identified fifty relevant studies investigating eight different serotonin receptor systems in a total of 684 patients and 675 controls. Meta-analysis of postmortem studies found an elevation in prefrontal 5-HT1A receptors with a moderate to large effect size (N=8, 85 patients and 94 controls, SMD=0.60; CI: 0.17-1.03; p=0.007) and a reduction with a large effect size in prefrontal 5-HT2A receptors (N=8, 168 patients and 163 controls, SMD=-0.73; CI: -1.33, -0.12; p=0.019) in schizophrenia vs healthy controls. The evidence for alterations in serotonin transporter availability or other serotonin receptors (5-HT1B; 5-HT1D; 5-HT3; 5-HT4; 5-HT7) is limited. There are fewer studies investigating 5-HT receptors in schizophrenia with neuroimaging. Findings indicated possible 5-HT alterations at psychosis onset, although due to the limited number it was not possible to combine studies in a meta-analysis. Further in vivo studies, particularly in drug naive patients using radiotracers that can index high affinity states, will help determine if the postmortem findings are primary or secondary to other factors.
Topics: Brain; Humans; Molecular Imaging; Receptors, Serotonin; Schizophrenia
PubMed: 24971825
DOI: 10.1016/j.neubiorev.2014.06.005 -
European Archives of Psychiatry and... Mar 2013The serotonin 1A receptor gene (HTR1A) has been associated with mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Therefore, we... (Meta-Analysis)
Meta-Analysis Review
The serotonin 1A receptor gene (HTR1A) has been associated with mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Therefore, we conducted a systematic review and meta-analysis between rs6295 (C-1019G) as well as rs878567 in HTR1A and MDs. Searching PubMed through May 2012, 15 studies, including our own, previously unpublished association study (135 MDD patients and 107 healthy controls), met inclusion criteria for the meta-analysis of rs6295 (4,297 MDs patients and 5,435 controls). Five association studies met criteria for the meta-analysis of rs878567 (2041MDs patients and 2,734 controls). rs6295 was associated with combined MDs (P allele model = 0.007 and P recessive model = 0.01). When divided by diagnostic subgroup (MDD = 3,119 patients and 4,380 controls or BP = 1,170 patients and 2,252 controls), rs6295 was associated with each MDs separately (MDD: P allele model = 0.006, P recessive model = 0.01; BP: P dominant model = 0.003). Likewise, rs878567 was associated with combined MDs (2,041 patients and 2,734 controls (P allele model = 0.0002, P dominant model = 0.0008, and P recessive model = 0.01). When divided by diagnostic subgroup (MDD = 1,013 patients and 1,728 controls or BP = 1,051 patients and 2,099 controls), rs878567 was associated with MDD (P allele model = 0.0007 and P dominant model = 0.01), while only one BP study had such data, precluding a meta-analysis. All of these significances survived correction for multiple comparisons. Results from this expanded meta-analysis, which included our own new study, suggest that rs6295 (C-1019G) and rs878567 in HTR1A are related to the pathophysiology of MDs, with overlap between MDD and BP. Findings provide additional clues to the underlying biology and treatment targets in MDs.
Topics: Adult; Aged; Bipolar Disorder; Case-Control Studies; Depressive Disorder, Major; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT1A
PubMed: 22752684
DOI: 10.1007/s00406-012-0337-4 -
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 -
Gene Nov 2013Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a common disorder with several predisposing factors, which may include genetic causes. Studies of the... (Meta-Analysis)
Meta-Analysis Review
Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a common disorder with several predisposing factors, which may include genetic causes. Studies of the association of susceptibility to and severity of OSAHS with the polymorphisms of the 5-HTR 2A/2C genes have had low statistical power and have yielded inconsistent results. To clarify the association we perform a meta-analysis that combines the genotyping data from all eligible published studies. We quantitatively analyzed five publications, which included a pool of 633 cases and 512 controls, addressing the 5-HT receptor polymorphism and the risk of OSAHS. Hardy-Weinberg equilibrium (HWE) and the minor allele frequency of genetic frequency distributions for the controls were calculated. Differences in the distribution of genotypes between cases and controls were compared by odds ratios (ORs) with their 95% confidence intervals (CIs). For each genetic model, data were pooled using fixed- or random-effects models, depending on the inter-publication heterogeneity. Our results from pooled data showed that individuals carrying the 5-HTR 2A -1438G/A AA genotype had an increased risk of OSAHS (OR=3.69, 95% CI=1.92-7.08) compared with those carrying the GG genotype. Significant results were also reached under a recessive model (OR=3.16, 95% CI=2.33-4.30, p<0.01). However, the results declined to an OR of 2.16 (95% CI=0.9-5.21) in a homozygote model when the studies were restricted to HWE. No statistically significant results concerning an association of the 102C/T polymorphism of the 5-HTR 2A gene with OSAHS were reached (p>0.05 for each genetic model). This meta-analysis suggested that the 5-HTR 2A -1438G/A genotype might modulate an elevated risk of OSAHS. No association of the 5-HTR 2A 102C/T genotype polymorphism with OSAHS was established. However, some publications exhibited HWE bias, which might influence the reliability of pooled data. Further studies in this field, using larger samples, better designs and additional ethnicities, are warranted.
Topics: Adult; Alleles; Case-Control Studies; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Models, Genetic; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Risk; Sleep Apnea, Obstructive
PubMed: 23988500
DOI: 10.1016/j.gene.2013.08.012 -
Annals of Palliative Medicine Apr 2021Researchers have not clearly determined whether adding aprepitant (ADH) to dexamethasone and one 5-HT3 receptor antagonist (DH) is clinically effective at preventing... (Meta-Analysis)
Meta-Analysis
Use of dexamethasone and a 5-HT3 receptor antagonist with or without aprepitant to prevent chemotherapy-induced nausea and vomiting among patients with lung cancer who are treated with platinum-based chemotherapy: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Researchers have not clearly determined whether adding aprepitant (ADH) to dexamethasone and one 5-HT3 receptor antagonist (DH) is clinically effective at preventing chemotherapy-induced nausea and vomiting (CINV) among patients with lung cancer (LC) treated with platinum-based chemotherapy (PBC). Therefore, we conducted a meta-analysis to examine the efficacy and safety of ADH and DH.
METHODS
We searched the PubMed, ScienceDirect, Cochrane Library, and Scopus databases, among others, for relevant studies. The primary outcomes were the complete response (CR) and the no nausea rate (NNR). The secondary endpoints were the number of patients who needed rescue antiemetic treatment (RAT), adverse events (AEs), and the Functional Living Index Emesis (FLIE) score.
RESULTS
We initially screened 2,118 articles; ultimately, four randomized controlled trials (RCTs) with 518 patients were included. The ADH group had a superior overall CR [risk ratio (RR): 1.16 (1.06, 1.27), P=0.002] and a lower number of patients who needed RAT [RR: 0.44 (0.29, 0.65), P<0.0001]. The ADH group also had a better overall NNR [RR: 1.11 (0.97, 1.26), P=0.12] and delayed CR [RR: 1.12 (0.97, 1.31), P=0.13]. No significant differences were observed in acute CR, acute NNR, or delayed NNR. In the subgroup analysis of the overall CR and NNR, ADH was superior in certain clinical characteristics (China, cisplatin-based chemotherapy, 2nd-generation 5-HT3 receptor antagonist, ADC <50%, and Eastern Cooperative Oncology Group (ECOG) score of 0-2). No significant differences in the AEs characterized as hematological or nonhematological toxicity were observed between the groups.
CONCLUSIONS
Compared with DH, ADH appears to be superior at preventing CINV and achieving a better CR among patients with LC treated with PBC.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; China; Dexamethasone; Humans; Lung Neoplasms; Morpholines; Nausea; Platinum; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Vomiting
PubMed: 33894731
DOI: 10.21037/apm-20-2290 -
Molecular Psychiatry Jul 2003The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they... (Meta-Analysis)
Meta-Analysis Review
The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite conclusions are difficult to establish. A reliable method for assessing individual studies and generating combined results is provided by systematic reviews using meta-analytical techniques. In this study, we carried out a systematic review of studies investigating 5-HT receptors and the 5-HTT in suicidal behavior. Studies were identified by means of MEDLINE database searches and by scanning reference lists. More than 190 articles were reviewed and 26 met the inclusion criteria. In all, 14 studies investigated six different 5-HT receptor loci and 12 studies investigated the 5-HTT promoter 44 bp insertion/deletion polymorphism. Two specific meta-analyses were carried out, pooling studies investigating the 5-HT2A 102 T/C and the 5-HTT promoter loci that included, respectively, a total of 1599 and 2539 subjects. The combined evidence was significant for association with the 5-HTT locus (Mantel-Haenszel weighted odds ratio (M-H(w) OR)=1.17 CI : 1.04-1.32, P=0.009), but not for the 5-HT2A 102 T/C variant (M-H(w) OR)=1.09 CI : 0.93-1.27, P=0.319). The 5-HTT result was robust and remained significant following sensitivity analysis, suggesting that 5-HTT may play a role in the predisposition to suicide.
Topics: Alleles; Amino Acid Substitution; Carrier Proteins; Case-Control Studies; Depression; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Polymorphism, Genetic; Promoter Regions, Genetic; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Self-Injurious Behavior; Serotonin Plasma Membrane Transport Proteins; Suicide; Suicide, Attempted
PubMed: 12874600
DOI: 10.1038/sj.mp.4001336 -
Neuroscience and Biobehavioral Reviews Mar 2023Cigarette smoking is often initiated during adolescence and an earlier age of onset is associated with worse health outcomes later in life. Paradoxically, the transition... (Review)
Review
Cigarette smoking is often initiated during adolescence and an earlier age of onset is associated with worse health outcomes later in life. Paradoxically, the transition towards adulthood also marks the potential for recovery, as the majority of adolescents are able to quit smoking when adulthood emerges. This systematic review aimed to evaluate the evidence from both human and animal studies for the differential impact of adolescent versus adult repeated and long-term tobacco and nicotine exposure on cognitive and brain outcomes. The limited human studies and more extensive yet heterogeneous animal studies, provide preliminary evidence of heightened fear learning, anxiety-related behaviour, reward processing, nicotinic acetylcholinergic receptors expression, dopamine expression and serotonin functioning after adolescent compared to adult exposure. Effects of nicotine or tobacco use on impulsivity were comparable across age groups. These findings provide novel insights into the mechanisms underlying adolescents' vulnerability to tobacco and nicotine. Future research is needed to translate animal to human findings, with a focus on directly linking a broader spectrum of brain and behavioural outcomes.
Topics: Animals; Humans; Adolescent; Adult; Nicotine; Tobacco Smoke Pollution; Nicotiana; Brain; Cognition
PubMed: 36627063
DOI: 10.1016/j.neubiorev.2023.105038 -
Molecular Psychiatry Jun 2003The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD)... (Review)
Review
The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). They have been investigated in a number of allelic association studies where the individual results have been inconsistent, and therefore, definite conclusions are difficult to make. Systematic reviews using meta-analytical techniques are a reliable method for objectively and reproducibly assessing individual studies and generating combined result. This study aimed at reviewing published studies investigating the association between affective disorders (MDD and BD) and variation at genes coding for serotonin receptors and the serotonin transporter. We performed National Library of Medicine database searches to identify potential studies. More than 430 articles were reviewed and 86 studies met the inclusion criteria for participation in our review. Of these, 41 studies investigated 45 different 5-HT receptor variants and 45 studies investigated at least one of two commonly studied 5-HTT polymorphisms in MDD. Many studies investigated the association between MDD and BD with the 5-HT2A 102 T/C, the 5-HTT promoter 44 bp insertion/deletion and the intron 2 VNTR polymorphisms, and thus, these could be pooled using meta-analytic techniques. The overall odds ratio (OR) for the combined individual results was significant for BD and the two 5-HTT polymorphisms: Mantel-Haenszel weighted OR=1.14, CI: 1.03-1.26, P=0.015 for the promoter locus (N=3467) and Mantel-Haenszel Weighted odds ratio OR=1.18, CI: 1.05-1.32, P=0.004 for the VNTR locus (N=3620). However, sensitivity analysis indicated that, in each case, the overall positive association could be mostly attributed to the large effect of one individual study. Therefore, these results suggest that, although promising, further studies are required to assess appropriately the evidence suggesting an association between BD and 5-HTT.
Topics: Carrier Proteins; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Mood Disorders; Nerve Tissue Proteins; Receptors, Serotonin; Serotonin Plasma Membrane Transport Proteins
PubMed: 12851635
DOI: 10.1038/sj.mp.4001328 -
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