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Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.
Antidepressive agents are one of the fastest-growing classes of prescribed drugs. However, the effects of antidepressive agents on bone density are controversial. The aim of this meta-analysis is to evaluate the state of research on the relationship between the use of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) and bone mineral density (BMD) in women. The database searched was Pubmed. The meta-analysis included human studies in women fulfilling the following criteria: (i) an assessment of bone mineral density in the lumbar spine, the femoral neck or the total hip; (ii) a comparison of the BMD of depressed individuals using antidepressive agents (SSRIs or TCAs), and a control group that did not use antidepressive agents; (iii) measurement of BMD using dual-energy X-ray absorptiometry (DXA); and (iv) calculations of the mean BMD and standard deviation or standard error. Four studies were identified, which, in total, included 934 women using antidepressive agents and 5767 non-using individuals. The results showed that no significant negative composite weighted mean effect sizes were identified for the comparisons between SSRI users and non-users. Similarly, no significant negative composite weighted mean effect sizes were identified for the comparisons between TCA users and non-users, indicating similar BMD in SSRI or TCA users and non-users. The meta-analysis shows that the association between antidepressant medication and bone mineral density has not been extensively researched. Only four studies fulfilled the inclusion criteria. The global result of the literature review and meta-analysis was that the use of antidepressive agents was not associated with lower or higher BMD. This result applies to both SSRIs and TCAs and to all measurement locations (lumbar spine, femoral neck and total hip).
Escitalopram is selective serotonin reuptake inhibitors (SSRIs) and one of the most commonly prescribed newer antidepressants (ADs) worldwide. We aimed to explore the efficacy, acceptability and tolerability of escitalopram in comparison with other ADs in the acute-phase treatment of major depressive disorder (MDD).
This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT₆, 5-HT1A, 5-HT2A, 5-HT₇, and dopamine D₂ receptors were evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT₆ receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as "druglikeness" in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as the most active 5-HT₆R agents within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, the most active one in the series (5-HT₆R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6⁻197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds form with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro.
Lavandula pubescens Decne (LP) is one of the three Lavandula species growing wildly in the Dead Sea Valley, Palestine. The products derived from the plant, including the essential oil (EO), have been used in Traditional Arabic Palestinian Herbal Medicine (TAPHM) for centuries as therapeutic agents. The EO is traditionally believed to have sedative, anti-inflammatory, antiseptic, antidepressive, antiamnesia, and antiobesity properties. This study was therefore aimed to assess the in vitro bioactivities associated with the LP EO. The EO was separated by hydrodistillation from the aerial parts of LP plants and analyzed for its antioxidant, antimicrobial, anticholinesterase, and antilipase activities. GC-MS was used for phytochemical analysis. The chemical analysis of the EO composition revealed 25 constituents, of which carvacrol (65.27%) was the most abundant. EO exhibited strong antioxidant (IC50 0.16-0.18 μL/mL), antiacetylcholinesterase (IC50 0.9 μL/mL), antibutyrylcholinesterase (IC50 6.82 μL/mL), and antilipase (IC50 1.08 μL/mL) effects. The EO also demonstrated high antibacterial activity with the highest susceptibility observed for Staphylococcus aureus with 95.7% inhibition. The EO was shown to exhibit strong inhibitory activity against Candida albicans (MIC 0.47 μL/mL). The EO was also shown to possess strong antidermatophyte activity against Microsporum canis, Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum (EC50 0.05-0.06 μL/mL). The high antioxidant, enzyme inhibitory, and antimicrobial potentials of the EO can, therefore, be correlated with its high content of monoterpenes, especially carvacrol, as shown by its comparable bioactivities indicators results. This study provided new insights into the composition and bioactivities of LP EO. Our finding revealed evidence that LP EO makes a valuable natural source of bioactive molecules showing substantial potential as antioxidant, neuroprotective, antihyperlipidemic, and antimicrobial agents. This study demonstrates, for the first time, that LP EO might be useful for further investigation aiming at integrative CAM and clinical applications in the management of dermatophytosis, Alzheimer's disease, and obesity.
Studies have investigated the risk of autism spectrum disorder (ASD) in children exposed in utero to antidepressant, with inconsistent results. Given the substantial public health implications on this topic, here, we presented an updated meta-analysis of the association between maternal antidepressant use during pregnancy and ASD. Cochrane Library, EMBASE, PsycINFO, and PubMed databases were systematically searched. A random effects model was used to pool the adjusted relative risk (RR) for cohort studies and the adjusted odds ratio (OR) for case-control studies as well as their corresponding 95% confidence intervals (CIs). Meta-analysis restricted to sibling studies was also conducted. Publication bias was systematically assessed. Fourteen studies were identified (eight cohort studies and six case-control studies). Pooled adjusted RR for cohort studies (n = 2,839,980) was 1.13 (0.93-1.39) showed a non-significant association; while two studies were potentially missing from the test of publication bias, filled estimates also showed a non-significant association (filled RR 0.97, 95% CI 0.79-1.19). Pooled OR was 1.51 (1.15-1.99) for case-control studies (n = 117,737) showed a significant association; two studies were potentially missing; however, the filled estimates suggested a non-significant association (filled OR 1.26, 95% CI 0.98-1.62). Analyses restricted to sibling studies also showed a non-significant association (RR 0.99, 95% CI 0.81-1.22). In summary, we did not evidence a significant association between maternal antidepressant use during pregnancy and ASD.
The second generation antipsychotic drug risperidone is widely used in the field of child and adolescent psychiatry to treat conditions associated with disruptive behavior, aggression and irritability, such as autism spectrum disorders. While risperidone can provide symptomatic relief for many patients, there is considerable individual variability in the therapeutic response and side-effect profile of the medication. One well established biological factor that contributes to these individual differences is genetic variation in the cytochrome P450 enzyme 2D6. The 2D6 enzyme metabolizes risperidone and therefore affects drug levels and dosing. In the present review, we summarize the current literature on 2D6 variants and their effects on risperidone responses, specifically in children and adolescents. Relevant articles were identified through systematic review, and after irrelevant articles were discarded, ten studies were included in the review. Most prospective studies were well controlled, but often did not have a large enough sample size to make robust statements about rarer variants, including those categorized as ultra-rapid and poor metabolizers. Individual studies demonstrated a role for different genetic variants in risperidone drug efficacy, pharmacokinetics, hyperprolactinemia, weight gain, extrapyramidal symptoms and drug-drug interactions. Where studies overlapped in measurements, there was typically a consensus between results. These findings indicate that the value of 2D6 genotyping in the youth population treated with risperidone requires further study, in particular with the less common variants.
Mounting evidence has shown that the risk of metabolic syndrome (MetS) is substantially overlapping in the diagnostic subgroups of psychiatric disorders. While it is widely acknowledged that patients receiving antipsychotic medications are at higher risk of MetS than antipsychotic-naive ones, the association between antidepressants and MetS is still debated. The goal of our mini review was to analyse the relationship among depressive symptoms, antidepressant use and the occurrence of MetS. Adhering to PRISMA guidelines, we searched MEDLINE, reference lists and journals, using the following search string: ((("Mental Disorders"[Mesh]) AND "Metabolic Syndrome"[Mesh]) AND "Antidepressive Agents"[Mesh]), and retrieved 36 records. Two reviewers independently assessed records and the mini review eventually included the data extracted from 8 studies. The Newcastle-Ottawa Scale was used to assess the quality of the selected studies. Overall, the results of the mini review seem to support the association among depressive symptoms, antidepressants therapy and MetS. Except for H1-R high-affinity ones, the relationship between antidepressants and MetS still needs to be clarified. Considering the widespread prescription of antidepressants, both on behalf of psychiatrists and primary care physicians, further research on this topic is recommended.
Gallic acid (GA) is a phenolic molecule found naturally in a wide range of fruits as well as in medicinal plants. It has many health benefits due to its antioxidant properties. This study focused on finding out the neurobiological effects and mechanisms of GA using published data from reputed databases. For this, data were collected from various sources, such as PubMed/Medline, Science Direct, Scopus, Google Scholar, SpringerLink, and Web of Science. The findings suggest that GA can be used to manage several neurological diseases and disorders, such as Alzheimer's disease, Parkinson's disease, strokes, sedation, depression, psychosis, neuropathic pain, anxiety, and memory loss, as well as neuroinflammation. According to database reports and this current literature-based study, GA may be considered one of the potential lead compounds to treat neurological diseases and disorders. More preclinical and clinical studies are required to establish GA as a neuroprotective drug.
Antidepressant drugs are mainly used to treat depression clinically. ABCB1 affects the P-glycoprotein activity and changes the amount of drugs in the blood tissue barrier that can be squeezed back into the blood, thus affecting the efficacy of antidepressants. In this present study, Meta-analysis was performed to further investigate the influences of ABCB1 gene polymorphism on antidepressant response.
Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy.
Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective.
Mapping non-canonical cellular pathways affected by approved medications can accelerate drug repurposing efforts, which are crucial in situations with a global impact such as the COVID-19 pandemic. Fluoxetine and fluvoxamine are well-established and widely-used antidepressive agents that act as serotonin reuptake inhibitors (SSRI-s). Interestingly, these drugs have been reported earlier to act as lysosomotropic agents, inhibitors of acid sphingomyelinase in the lysosomes, and as ligands of sigma-1 receptors, mechanisms that might be used to fight severe outcomes of COVID-19. In certain cases, these drugs were administered for selected COVID-19 patients because of their antidepressive effects, while in other cases, clinical studies were performed to assess the effect of these drugs on treating COVID-19 patients. Clinical studies produced promising data that encourage the further investigation of fluoxetine and fluvoxamine regarding their use in COVID-19. In this review, we summarize experimental data and the results of the performed clinical studies. We also provide an overview of previous knowledge on the tissue distribution of these drugs and by integrating this information with the published experimental results, we highlight the real opportunity of using these drugs in our fight against COVID-19.
Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The purpose of the current systematic review is to evaluate the therapeutic efficacy of pharmacological treatments on measures of anhedonia in adults with MDD. Electronic databases Cochrane Library (CENTRAL), Ovid MEDLINE, PubMed, PsycINFO, and Google Scholar were searched from inception to June 1, 2018 for longitudinal studies utilizing pharmacotherapy for the treatment of anhedonia in patients with MDD. A total of 17 eligible studies were identified (i.e., evaluated the effects of pharmacotherapy on a measure of anhedonia). Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Based on the available evidence, most antidepressants demonstrated beneficial effects on measures of anhedonia as well as the other depressive symptoms. Only escitalopram/riluzole combination treatment was ineffective in treating symptoms of anhedonia in MDD. Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms.
Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41-50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01-1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10-54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35-37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment-if ethically permissible-to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the verum effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings.
Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness information from randomised controlled trials (RCTs) of ADM versus psychotherapy for MDD at the symptom level and develops and tests the Symptom-Oriented Therapy (SOrT) metric for precision treatment allocation.
To analyse to what extent clinical practice guidelines on drug treatment of depression in children and adolescents mention the risk of adverse effects, to characterise the citations in the guidelines and to assess to what extent data from a major study (Treatment for Adolescents With Depression Study, TADS) was used as basis for information about adverse effects.
Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1-10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1-15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5-HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.
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