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Aims Methods Results Conclusions This study aimed to provide a comprehensive view of cardiovascular adverse events (AEs) associated with venlafaxine (VEN) therapy.Cardiovascular AE reports for patients receiving VEN therapy were retrieved from January 2004 to December 2023 from the FDA Adverse Event Reporting System database. Effects of age, sex and daily VEN dose on the occurrence of different types of cardiovascular AEs and the influence of demographics, VEN dose, comorbidity and co‐medication on death in patients with cardiovascular AEs were analysed by multivariate logistic regression analysis.The study included 16 110 AE reports following VEN treatment (median age: 51 years, females: 69.78%, median VEN daily dose: 100 mg/day). VEN daily dose was associated with increased risks of cardiac arrhythmias, embolic and thrombotic events, torsade de pointes/QT prolongation, ischaemic heart disease, cardiac failure, cardiomyopathy and overall cardiovascular events. The elderly (≥ 75 years), male sex, comorbidity (infections and infestations, cardiac disorders, nervous system disorders) and co‐medication (quetiapine and clozapine) were related to death following VEN‐associated cardiovascular AEs; however, the risk of cardiovascular death did not increase with regular VEN doses.Our study confirmed the association of cardiovascular AEs with VEN therapy and revealed the influencing factors for the risk of VEN‐related cardiovascular AEs and death due to these events. Based on the obtained evidence, the cardiovascular health of late‐elderly patients with complex comorbidity and polytherapy should be closely monitored when they receive VEN therapy. As an exploratory study, prospective studies are needed to validate our findings in the future. [ABSTRACT FROM AUTHOR]

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPSinduced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels. [ABSTRACT FROM AUTHOR]

The task of a psychiatrist is to select the most appropriate medication or combination of drugs to treat the symptoms of schizophrenia while minimizing the risk of side effects and ensuring the patient achieves the highest level of functioning possible. This is a challenging task as the action of each drug or group of drugs is different. The efficacy of cariprazine, which affects D3 receptors as a D3/D2 receptor partial agonist, has been extensively studied and is one of the first medication choices by practicing psychiatrists when treating patients with negative symptomatology. In this clinical case, we demonstrate the effective and safe treatment of a patient's positive and affective symptoms using a combination of cariprazine, clozapine, and venlafaxine. [ABSTRACT FROM AUTHOR]

Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP. [ABSTRACT FROM AUTHOR]

Over the past three decades, oral controlled-release dosage forms have been developed due to their therapeutic advantages, such as ease of administration, patient compliance, and flexibility in formulation. However, this approach has faced physiological difficulties, such as the inability to contain and position the controlled drug delivery system within the desired region of the gastrointestinal tract (GIT) due to variable gastric emptying and motility. Venlafaxine is an antidepressant and a serotonin and norepinephrine reuptake inhibitor (SNRI). Its active metabolite, desvenlafaxine, works by blocking the reuptake of serotonin and norepinephrine, which are key neurotransmitters in mood regulation. Gastroretentive dosage forms can stay in the gastric region for several hours and significantly prolong the gastric residence time of drugs. Natural materials have been extensively used in drug delivery because they are readily available, cost-effective, eco-friendly, capable of many chemical modifications, potentially degradable, and compatible due to their natural origin. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P＜0.001) and low spontaneous alteration(P＜0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P＜0.001) and more spontaneous alteration(P＜0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P＜0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P＜0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus.

Objective To observe the effects of 20 Hz repetitive transcranial magnetic stimulation (rTMS) combined with venlafaxine in the treatment of adult generalized anxiety disorder (GAD) and its impact on cognitive function and negative emotions. Methods A total of 75 adult patients with GAD admitted to the hospital from March 2021 to April 2023 were randomly divided into two groups using the random number table method. The control group (37 cases) received venlafaxine treatment, while the study group (38 cases) received rTMS on the basis of venlafaxine. The clinical efficacy of the two groups was compared. Results The total effective rate eye movement measurement. Montreal Cognitive Assessment Scale (MOCA) scores in the study group were higher than those in the control group and the event-related potential latency, as well as the scores of GAD-7 scale, Hamilton Anxiety Scale and Hamilton Depression Scale were significantly lower than those of the control group, with statistical significance (P<0.05). Conclusion The 20 Hz repetitive transcranial magnetic stimulation combined with venlafaxine therapy can improve the clinical efficacy, cognitive function, and alleviate negative emotions in adult patients with GAD, with high therapeutic practicality. [ABSTRACT FROM AUTHOR]

Schematic representation of the role of reactive astrocyte-activated microglia crosstalk in triggering neuroinflammation and neuronal endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in astrocytic σ-1 receptor inhibition mice. Astrocyte σ-1 receptor deficiency leads to NF-κB entry into the nucleus to activate inflammation-related pathways, which will produce and release large amounts of inflammatory mediators (TNF, IL-6, etc.). These inflammatory mediators may lead to the activation of microglia to produce more pro-inflammatory mediators, which, in turn, may promote the astrocytes to further release more inflammatory factors. This crosstalk appears to amplify neuroinflammation, and ultimately, this powerful inflammatory storm leads to neuronal stress, resulting in excessive neuronal apoptosis and causing depressive-like behavior in mice. YL-0919 treatment not only disrupts the amplification of inflammation caused by this mutual crosstalk, but also alleviates neuronal apoptosis, ultimately relieving depressive-like behavior in mice. (Created by Biorender). [Display omitted] • Selective σ-1 receptor agonist, YL-0919 alleviates depressive-like behavior in CRS-induced mice within 1 week. • Astrocytes underly the faster onset antidepressant effect of YL-0919. • mPFC astrocytic σ-1 receptor deficiency induces depressive-like behaviors in mice. • Reactive astrocyte and activated microglia crosstalk amplify neuroinflammation. • Sigma-1 receptor is a key regulator that maintains inflammatory homeostasis in the brain. Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs. [ABSTRACT FROM AUTHOR]

Background: Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement. Methods: Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant‐free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment. Results: A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness. Conclusion: Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes. [ABSTRACT FROM AUTHOR]

Background: Venlafaxine dose regimens vary considerably between individuals, requiring personalized dosing. Aim: This study aimed to identify dose-related influencing factors of venlafaxine through real-world data analysis and to construct a personalized dose model using advanced artificial intelligence techniques. Method: We conducted a retrospective study on patients with depression treated with venlafaxine. Significant variables were selected through a univariate analysis. Subsequently, the predictive performance of seven models (XGBoost, LightGBM, CatBoost, GBDT, ANN, TabNet, and DT) was compared. The algorithm that demonstrated optimal performance was chosen to establish the dose prediction model. Model validation used confusion matrices and ROC analysis. Additionally, a dose subgroup analysis was conducted. Results: A total of 298 patients were included. TabNet was selected to establish the venlafaxine dose prediction model, which exhibited the highest performance with an accuracy of 0.80. The analysis identified seven crucial variables correlated with venlafaxine daily dose, including blood venlafaxine concentration, total protein, lymphocytes, age, globulin, cholinesterase, and blood platelet count. The area under the curve (AUC) for predicting venlafaxine doses of 75 mg, 150 mg, and 225 mg were 0.90, 0.85, and 0.90, respectively. Conclusion: We successfully developed a TabNet model to predict venlafaxine doses using real-world data. This model demonstrated substantial predictive accuracy, offering a personalized dosing regimen for venlafaxine. These findings provide valuable guidance for the clinical use of the drug. [ABSTRACT FROM AUTHOR]

Background: Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary. Aim: Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques. Method: Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations. Results: A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value. Conclusion: The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are reported to cause stress cardiomyopathy (SC). This study evaluated the association between SSRI/SNRI use and the occurrence of cardiomyopathy in the publicly available U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionate analysis and likelihood ratio tests were used to identify risk associated with SSRIs or SNRIs and the incidence of SC, using data from between from 2012 to 2022 acquired from the FAERS database. The study identified 132 individual case safety reports (ICSRs) of SC associated with SSRIs or SNRIs. Venlafaxine (48%) and fluoxetine (27%) were the most common antidepressants of the ICSRs. Approximately 80% of SC cases were reported in females, with individuals aged 45–65 years identified as a high-risk population. Both venlafaxine (ratio-scale information component [RSIC] 2.54, 95% CI 2.06–3.04) and fluoxetine (RSIC 3.20, 95% CI 2.31–4.47) were associated with SC, with likelihood ratio estimates of 3.55 (p = 0.02) for venlafaxine and 4.82 (p = 0.008) for fluoxetine. The median time to cardiomyopathy onset was 20 days, with hospitalization reported in 48.33% of patients. Venlafaxine and fluoxetine were associated with SC risk, particularly in middle-aged women. Caution should be exercised when using SSRIs or SNRIs combined with other serotonergic medications. [ABSTRACT FROM AUTHOR]

Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin–norephinephrine reuptake inhibitor antidepressant) to freshwater ecosystems at levels causing adverse metabolic effects on fish. Changes to fish metabolism can be regulated by epigenetic mechanisms like microRNA (small RNA molecules that regulate mRNA translation), including regulating mitochondrial mRNAs. Nuclear‐encoded microRNAs regulate mitochondrial gene expression in mammals, and have predicted effects in fish. We aimed to identify whether venlafaxine exposure changed mitochondrial respiration and resulted in differentially abundant mitochondrial microRNA (mitomiRs) in zebrafish brains. In vitro exposure of brain homogenate to below environmentally relevant concentrations of venlafaxine (<1 µg/L) caused a decrease in mitochondrial respiration, although this was not driven by changes to mitochondrial Complex I or II function. To identify whether these effects occur in vivo, zebrafish were exposed to 1 µg/L venlafaxine for 0, 1, 6, 12, 24, and 96 h. In vivo, venlafaxine exposure had no significant effects on brain mitochondrial respiration; however, select mitomiRs (dre‐miR‐301a‐5p, dre‐miR‐301b‐3p, and dre‐miR‐301c‐3p) were also measured, because they were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI) abundance. These mitomiRs were differentially regulated based on venlafaxine exposure (with miR‐301c‐3p abundance differing during the day and miR‐301b‐3p being lower in exposed fish at night), and with respect to sex and time sampled. Overall, the results demonstrated that in vitro venlafaxine exposure to zebrafish brain caused a decrease in mitochondrial respiration, but these effects were not seen after acute in vivo exposure. Results may have differed because in vivo exposure allows for fish to mitigate effects through mechanisms that could include mitomiR regulation, and because fish were only acutely exposed. Environ Toxicol Chem 2024;43:1569–1582. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Background: Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZtreated mice are largely unclear. Methods: Male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage fromthe third week onward during CPZ treatment. Results: CPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of Lactobacillus and Bifidobacterium in CPZ-treated mice. Conclusion: The anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice. [ABSTRACT FROM AUTHOR]

Objectives: Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination." Results: A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58–0.77) and 0.63 (95%CI 0.43–0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49–2.13). Conclusions: This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P＜0.001) and low spontaneous alteration(P＜0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P＜0.001) and more spontaneous alteration(P＜0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P＜0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P＜0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus. [ABSTRACT FROM AUTHOR]

Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000−2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18–80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95–1.00), fluoxetine (0.94, 95 % CI, 0.92–0.95), and venlafaxine (0.90, 95 % CI, 0.87–0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82–0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram. • Users of all study antidepressants had similar infection risks compared to citalopram. • Healthcare utilization causes significant residual surveillance bias. • Use of antidepressants was not associated with an altered risk of SARS-CoV-2 infection compared to citalopram. [ABSTRACT FROM AUTHOR]

Background and Objective: Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. Methods: A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration–time curve from time zero to the last sampling time (AUC0–t) and the maximum observed concentration (Cmax). Results: A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0–t and Cmax of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80–125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. Conclusions: Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. Clinical Trials Registration: This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform (http://www.chinadrugtrials.org.cn/index.html) with registration number CTR20211243, date: June 1, 2021. [ABSTRACT FROM AUTHOR]

The article focuses on a study comparing weight gain risk across eight commonly used antidepressants, finding bupropion associated with the least weight gain and varying weight effects for other drugs over 6, 12, and 24 months.

Abstract The new era of solid contact ion selective electrodes (SC-ISEs) miniaturized design has received an extensive amount of concern. Because it eliminated the requirement for ongoing internal solution composition optimization and created a two-phase system with stronger detection limitations. Herein, the determination of venlafaxine HCl is based on a comparison study between different ion- to electron transduction materials (such as; multiwalled carbon nanotubes (MWCNTs), polyaniline (PANi), and ferrocene) and illustrating their mechanisms in their applied sensors. Their different electrochemical features (such as bulk resistance (Rb**), double-layer capacitance (Cdl), geometric capacitance (Cg), and specific capacitance (Cp)) were evaluated and discussed by using the Electrochemical Impedance Spectroscopy (EIS), Chronopotentiometry (CP), and Cyclic Voltammetry (CV) experiments. The results indicated that each transducer's influence on the proposed sensor's electrochemical characteristics is determined by their unique chemical and physical properties. The electrochemical features vary for different solid contact materials used in transduction mechanisms. The results confirm that the MWCNT sensor revealed the best electrochemical behavior with the potentiometric response of a near-Nernestian slope of 56.1 ± 0.8 mV/decade with detection limits of 3.8 × 10−6 mol/L (r2 = 0.999) and a low potential drift (∆E/∆t) of 34.6 µV/s. Also, the selectivity study was performed in the presence of different interfering species either in single or complex matrices. This demonstrates excellent selectivity, stability, conductivity, and reliability as a VEN-TPB ion pair sensor for accurately measuring VEN in its various formulations. The proposed method was compared to HPLC reported technique and confirmed no significant difference between them. So, the proposed sensors fulfill their solutions' demand features for VEN appraisal.

Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group (p < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine (p < 0.05 central zone; p ≤ 0.05 periphery zone) and SMe1EC2M3 (p < 0.05 central zone; p < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST (p < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group (p < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group (p < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD. [ABSTRACT FROM AUTHOR]

Research on long-term pharmacotherapy for trauma-affected refugees is scarce. The purpose of this follow-up study of a randomised trial was to investigate the effects of sertraline compared to venlafaxine in combination with psychotherapy, 6 and 18 months after end of trial. The primary outcome was PTSD symptoms, measured by the Harvard Trauma Questionnaire (HTQ). The secondary outcomes included: Hopkins Symptom Checklist-25 (HSCL-25), somatisation items of the Symptoms Checklist-90 (SCL), pain on a visual analogue scale, well-being on the WHO-5, Sheehan Disability Scale, Hamilton Depression and Anxiety scales and Global Assessment of Functioning. Moreover, the shorter version of the Recent Life Events (IRLE) was adopted to obtain information regarding the patients' treatment and life events between the follow-up periods. Out of 195 patients eligible for intention-to-treat analyses during trial, 116 participated in the 6-month follow-up and 97 participated in the 18-month follow-up. The results of our intention-to-treat analyses revealed no significant long-term differences between the groups on the primary outcome assessing PTSD symptoms (HTQ). For the secondary outcomes significant differences were found at the 18-month follow-up in favour of venlafaxine assessing symptoms of anxiety, depression and somatisation (HSCL-25 and SCL), although only in intention-to-treat and not per-protocol analyses. No conclusions could be drawn due to conflicting results between our intention-to-treat and per-protocol analyses. [ABSTRACT FROM AUTHOR]

Background: Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega‐analyses of prospective trials of individual participant‐level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy. Methods: Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (n = 393) were aggregated into an IPD dataset (i.e., mega‐analysis). Hierarchical log‐linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI/S) and change (CGI/C) scores, and change over time in Young Mania Rating (YMR) scores. Results: Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (b = −2.33, t = −6.68, p < 0.0001), significantly greater symptom reduction on the CGI/S across time (b = −0.414, t = −6.32, p < 0.001), and a significant improvement in CGI/C across time (b = −0.47, t = −7.43, p < 0.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (b = 0.06, t = 0.49, p = 0.62). Conclusion: Findings from this IPD mega‐analysis of bipolar II depression trials suggest a divergence from current evidence‐based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega‐analysis suggests that antidepressant monotherapy may provide superior short‐term effectiveness without clinically meaningful increase in treatment‐emergent hypomanic symptoms compared to lithium monotherapy. [ABSTRACT FROM AUTHOR]

• Territorial aggression in a 2-year-old dog. • Treatment with venlafaxine and clonidine. • Did not respond to fluoxetine or sertraline. • Positive outcome. A 2-year-old intact male German Shepherd dog was presented for aggressive behavior toward unfamiliar people. The aggressive behavior was limited to the yard and home of the owner. The dog was diagnosed with territorial aggression. The patient had not responded to two different selective serotonin reuptake inhibitors (fluoxetine, sertraline) before responding to a combination of venlafaxine extended release and clonidine. [ABSTRACT FROM AUTHOR]

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is indicated for the treatment of major depressive disorder, social anxiety disorder, generalized anxiety disorder, and panic disorder. Venlafaxine is metabolized to the active metabolite desvenlafaxine mainly by CYP2D6. Genetic polymorphism of CYP2D6 and coadministration with other medications can significantly affect the pharmacokinetics and/or pharmacodynamics of venlafaxine and its active metabolite. This study aimed to establish the PBPK models of venlafaxine and its active metabolite related to CYP2D6 genetic polymorphism and to predict drug–drug interactions (DDIs) with clarithromycin and paroxetine in different CYP2D6 genotypes. Clinical pharmacogenomic data for venlafaxine and desvenlafaxine were collected to build the PBPK model. Physicochemical and absorption, distribution, metabolism, and excretion (ADME) characteristics of respective compounds were obtained from previously reported data, predicted by the PK-Sim® software, or optimized to capture the plasma concentration–time profiles. Model evaluation was performed by comparing the predicted pharmacokinetic parameters and plasma concentration–time profiles to the observed data. Predicted plasma concentration–time profiles of venlafaxine and its active metabolite were visually similar to the observed profiles and all predicted AUC and Cmax values for respective compounds were included in the twofold error range of observed values in non-genotyped populations and different CYP2D6 genotypes. When clarithromycin or clarithromycin plus paroxetine was concomitantly administered, predicted plasma concentration–time profiles of venlafaxine properly captured the observed profiles in two different CYP2D6 genotypes and all predicted DDI ratios for AUC and Cmax were included within the acceptance range. Consequently, the present model successfully captured the pharmacokinetic alterations of venlafaxine and its active metabolite according to CYP2D6 genetic polymorphism as well as the DDIs between venlafaxine and two CYP inhibitors. The present model can be used to predict the pharmacokinetics of venlafaxine and its active metabolite considering different races, ages, coadministered drugs, and CYP2D6 activity of individuals and it can contribute to individualized pharmacotherapy of venlafaxine. [ABSTRACT FROM AUTHOR]

In this study, we aimed to improve upon a published population pharmacokinetic (PK) model for venlafaxine (VEN) in the treatment of depression in older adults, then investigate whether CYP2D6 metabolizer status affected model‐estimated PK parameters of VEN and its active metabolite O‐desmethylvenlafaxine. The model included 325 participants from a clinical trial in which older adults with depression were treated with open‐label VEN (maximum 300 mg/day) for 12 weeks and plasma levels of VEN and O‐desmethylvenlafaxine were assessed at weeks 4 and 12. We fitted a nonlinear mixed‐effect PK model using NONMEM to estimate PK parameters for VEN and O‐desmethylvenlafaxine adjusted for CYP2D6 metabolizer status and age. At both lower doses (up to 150 mg/day) and higher doses (up to 300 mg/day), CYP2D6 metabolizers impacted PK model‐estimated VEN clearance, VEN exposure, and active moiety (VEN + O‐desmethylvenlafaxine) exposure. Specifically, compared with CYP2D6 normal metabolizers, (i) CYP2D6 ultra‐rapid metabolizers had higher VEN clearance; (ii) CYP2D6 intermediate metabolizers had lower VEN clearance; (iii) CYP2D6 poor metabolizers had lower VEN clearance, higher VEN exposure, and higher active moiety exposure. Overall, our study showed that including a pharmacogenetic factor in a population PK model could increase model fit, and this improved model demonstrated how CYP2D6 metabolizer status affected VEN‐related PK parameters, highlighting the importance of genetic factors in personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Venlafaxine (VEN) is a commonly utilized medication for alleviating depression and anxiety disorders. The presence of genetic polymorphisms gives rise to considerable variations in plasma concentrations across different phenotypes. This divergence in phenotypic responses leads to notable differences in both the efficacy and tolerance of the drug. Purpose: A physiologically based pharmacokinetic (PBPK) model for VEN and its metabolite O-desmethylvenlafaxine (ODV) to predict the impact of CYP2D6 and CYP2C19 gene polymorphisms on VEN pharmacokinetics (PK). Methods: The parent-metabolite PBPK models for VEN and ODV were developed using PK-Sim® and MoBi®. Leveraging prior research, derived and implemented CYP2D6 and CYP2C19 activity score (AS)-dependent metabolism to simulate exposure in the drug-gene interactions (DGIs) scenarios. The model's performance was evaluated by comparing predicted and observed values of plasma concentration–time (PCT) curves and PK parameters values. Results: In the base models, 91.1%, 94.8%, and 94.6% of the predicted plasma concentrations for VEN, ODV, and VEN + ODV, respectively, fell within a twofold error range of the corresponding observed concentrations. For DGI scenarios, these values were 81.4% and 85% for VEN and ODV, respectively. Comparing CYP2D6 AS = 2 (normal metabolizers, NM) populations to AS = 0 (poor metabolizers, PM), 0.25, 0.5, 0.75, 1.0 (intermediate metabolizers, IM), 1.25, 1.5 (NM), and 3.0 (ultrarapid metabolizers, UM) populations in CYP2C19 AS = 2.0 group, the predicted DGI AUC0-96 h ratios for VEN were 3.65, 3.09, 2.60, 2.18, 1.84, 1.56, 1.34, 0.61, and for ODV, they were 0.17, 0.35, 0.51, 0.64, 0.75, 0.83, 0.90, 1.11, and the results were similar in other CYP2C19 groups. It should be noted that PK differences in CYP2C19 phenotypes were not similar across different CYP2D6 groups. Conclusions: In clinical practice, the impact of genotyping on the in vivo disposition process of VEN should be considered to ensure the safety and efficacy of treatment. [ABSTRACT FROM AUTHOR]

Currently, there is no confirmed drug intervention in the treatment of methamphetamine (MA) dependence. In the present study, we tested the possible influence of venlafaxine in individuals with MA dependence. A total of 52 male patients (mean age: 33.93 years) diagnosed with MA dependence referred to Farabi Hospital in Kermanshah, Iran, was randomly assigned either to enlafaxine or a placebo condition. At the baseline, as well as 4 to 8 weeks later, patients completed questionnaires on depression, withdrawal symptoms, and cravings. The mean scores of withdrawal symptoms (hyperarousal, anxiety, reversed vegetative), depression, and cravings (desire & intention, negative reinforcement, and control) during the study and in both groups had a descending trend. Unlike the effect of the studied groups, the effect of time on the repeated measure model was significant. The mean of inverse symptoms, desire, and control from the fourth week to the end of the study did not have a statistically significant difference. The results showed that venlafaxine can be effective in reducing depression, withdrawal symptoms, and cravings in people who are dependent on MA, though these results were observed in parallel in the placebo group, and as such warrants further study. [ABSTRACT FROM AUTHOR]

Molecular autopsy is a very important tool in forensic toxicology. However, many determinants, such as co-medication and physiological parameters, should be considered for optimal results. These determinants could cause phenoconversion (PC), a discrepancy between the real metabolic profile after phenoconversion and the phenotype determined by the genotype. This study's objective was to assess the PC of drug-metabolizing enzymes, namely CYP2D6, 2C19, and 3A4, in 45 post-mortem cases where medications that are substrates, inducers, or inhibitors of these enzymes were detected. It also intended to evaluate how PC affected the drug's metabolic ratio (MR) in four cases. Blood samples from 45 cases of drug-related deaths were analyzed to detect and determine drug and metabolite concentrations. Moreover, all the samples underwent genotyping utilizing the HaloPlex Target Enrichment System for CYP2D6, 2C19, and 3A4. The results of the present study revealed a statistically significant rate of PC for the three investigated enzymes, with a higher frequency of poor metabolizers after PC. A compatibility was seen between the results of the genomic evaluation after PC and the observed MRs of venlafaxine, citalopram, and fentanyl. This leads us to focus on the determinants causing PC that may be mainly induced by drug interactions. This complex phenomenon can have a significant impact on the analysis, interpretation of genotypes, and accurate conclusions in forensic toxicology. Nevertheless, more research with more cases in the future is needed to confirm these results. [ABSTRACT FROM AUTHOR]

The new era of solid contact ion selective electrodes (SC-ISEs) miniaturized design has received an extensive amount of concern. Because it eliminated the requirement for ongoing internal solution composition optimization and created a two-phase system with stronger detection limitations. Herein, the determination of venlafaxine HCl is based on a comparison study between different ion- to electron transduction materials (such as; multiwalled carbon nanotubes (MWCNTs), polyaniline (PANi), and ferrocene) and illustrating their mechanisms in their applied sensors. Their different electrochemical features (such as bulk resistance (Rb**), double-layer capacitance (Cdl), geometric capacitance (Cg), and specific capacitance (Cp)) were evaluated and discussed by using the Electrochemical Impedance Spectroscopy (EIS), Chronopotentiometry (CP), and Cyclic Voltammetry (CV) experiments. The results indicated that each transducer's influence on the proposed sensor's electrochemical characteristics is determined by their unique chemical and physical properties. The electrochemical features vary for different solid contact materials used in transduction mechanisms. The results confirm that the MWCNT sensor revealed the best electrochemical behavior with the potentiometric response of a near-Nernestian slope of 56.1 ± 0.8 mV/decade with detection limits of 3.8 × 10−6 mol/L (r2 = 0.999) and a low potential drift (∆E/∆t) of 34.6 µV/s. Also, the selectivity study was performed in the presence of different interfering species either in single or complex matrices. This demonstrates excellent selectivity, stability, conductivity, and reliability as a VEN-TPB ion pair sensor for accurately measuring VEN in its various formulations. The proposed method was compared to HPLC reported technique and confirmed no significant difference between them. So, the proposed sensors fulfill their solutions' demand features for VEN appraisal. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype. Methods: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs). Results: A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive. Conclusion: The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants. [ABSTRACT FROM AUTHOR]

The article focuses on exploring genetic polymorphisms as potential contributors to severe postoperative pain. Topics include the use of pharmacogenetics in pain therapy to predict individual analgesic response, the impact of genetic variants on opioid metabolism, and the influence of genetic polymorphisms on the effectiveness of analgesics in specific patient populations, such as those with red hair.

The article discusses the exponential development of research on carbon-based nanomaterials, such as carbon nanotubes and graphene, and their applications in various fields including electronics, energy storage, biomedicine, and sensing. It highlights the use of electrospinning as a technique for processing carbon nanotubes and their composites, as well as the potential of graphene oxide as a sensitive material for dosimeters. The article also mentions the use of carbon nanomaterials in energy storage devices and their potential as antimicrobial agents. Overall, the article provides an overview of the current research and potential applications of carbon-based nanomaterials. [Extracted from the article]

This study aimed to explore male-female differences in suicide ideation (SI) and suicide risk factors in major depressive disorder (MDD). We analysed 482 adults (sample 1) and 438 elderly outpatients (sample 2) with MDD. Sample 1 was treated with different antidepressant combinations (escitalopram; bupropion plus escitalopram; venlafaxine plus mirtazapine) and assessed by means of the Concise Health Risk Tracking (SI), Quick Inventory of Depressive Symptomatology, Altman Mania Rating Scale and Psychiatric Diagnostic Screening Questionnaire. Sample 2 was treated with venlafaxine and assessed using the Hamilton scale for depression, Anxiety Sensitivity Index and Penn State Worry Questionnaire for anxiety, Beck Scale for Suicide Ideation and Repeatable Battery for the Assessment of Neuropsychological Status. In sample 1, females had greater depression severity (O.R 0.961 99%CI: 0.929 − 0.995), males reported more alcohol abuse (O.R 1.299 99%CI: 1.118 − 1.509) and active SI (O.R 1.109 99%CI: 1.005 − 1.255). In sample 2 men showed more severe SI (O.R 1.067; 99%CI: 1.014 − 1.122) and weight loss (OR = 5.89 99%CI: 1.01 − 34.19), women more gastrointestinal symptoms. In these selected samples, although women had more severe depression, men had more suicide risk factors. Such differences might contribute to men's increased suicide risk. In major depressive disorder sex differences affect the clinical expression of depressive episodes. In comparison to men, women endorse higher levels of overall depression in adult MDD and more somatic anxiety and gastrointestinal symptoms in late-life MDD. After controlling for confounding variables, males have more severe SI and a larger number of suicide risk factors (eg. alcohol abuse; weight loss). The association between male sex and SI is detectable in both adults and elderly patients with MDD. Further studies are necessary to elucidate how sex differences in suicide ideation and suicide risk factors are related to men's increased suicide risk. [ABSTRACT FROM AUTHOR]

Aims: To explore the pharmacological treatment of vascular depression (VaDep) and whether the blood levels of neurotransmitters can reflect the VaDep severity. Methods: VaDep patients with somatic symptoms were enrolled and randomly received venlafaxine + tandospirone (Combined Group) or venlafaxine (Monotherapy Group). The treatment efficacy was assessed by Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire‐15 (PHQ‐15). The levels of blood monoamine neurotransmitters were measured by enzyme‐linked immunosorbent assay. Results: Both groups reported a progressive decrease in HAMD, HAMA, and PHQ‐15 scores to below the baseline after the respective treatment. Compared with the Monotherapy Group, the Combined Group reported a significant decrease in HAMD score at week 2 and markedly lower HAMA and PHQ‐15 scores at weeks 1, 2, 4, and 8. Both groups showed a decrease in the levels of blood monoamine neurotransmitters at weeks 4 and 8 when compared with the baseline. A strong positive association was evident between the plasma 5‐HT levels and the HAMD score. Conclusion: The combined therapy rapidly acts on VaDep comorbid with anxiety and somatic symptoms and significantly alleviates the anxiety and somatic symptoms. The plasma levels of 5‐HT may serve as potential objective candidates in evaluating VaDep severity and the efficacy of the undertaken treatment regimen. [ABSTRACT FROM AUTHOR]

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.

Dear Editor, the first antidepressant medication of the serotonin-norepinephrine reuptake inhibitor class is venlafaxine (effexor), which is taken orally with a half-life of 5 hours; however, its effective and chief metabolite (i.e., O-desmethylvenlafaxine) owns a half-life of 11 hours. [...]

BackgroundCuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear.MethodsMale C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment.ResultsCPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of Lactobacillus and Bifidobacterium in CPZ-treated mice.ConclusionThe anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.

Abstract Introduction The aim of this study is to assess the effectiveness of serotonin-norepinephrine reuptake inhibitors (SNRIs) in managing ADHD symptoms compared to placebo, stimulants, or compared as pre- and post-treatment. Methods Clinical trials assessing the potency of SNRIs in treating ADHD patients were imported from PubMed, Web of Science, and Scopus (until February 2023). Data were extracted by two independent researchers. Random- and fixed- effect meta-analysis was performed to pool the data. Publication bias and study heterogeneity were assessed. The Cochrane Collaboration tool was utilized to determine the risk of bias. The certainty of outcomes was evaluated by the Grade criteria. Results Of the initial 830 studies, 13 were finally imported after two screening stages which two separate researchers carried out. The pooled standardized mean difference (95% CI) of reducing the score of different ADHD questionnaires (showing reduction in total inattentive and hyperactivity/impulsivity symptoms) by SNRIs, venlafaxine, and duloxetine were − 2.20 [− 3.00, − 1.40], − 1.86 [− 2.69, − 1.02], − 2.65 [− 3.35, − 1.96], respectively. While the most reported side effects were nausea, abdominal pain, and sedation, all studies reported that side effects were not serious and were well tolerated. Outcomes for the effectiveness of venlafaxine and duloxetine got high and moderate certainty, respectively. Conclusions Duloxetine and venlafaxine can be administered to treat symptoms of ADHD while being well tolerated. It seems that duloxetine is more potent in reducing ADHD symptoms. It can also be concluded that venlafaxine is more effective in females, and is more effective on inattentive symptoms of ADHD rather than hyperactive symptoms.

Abnormal and excessive desire to smell certain odors or objects (desiderosmia) is reported to be seen with iron deficiency anemia. We present here four cases of desiderosmia in diagnosed patients of major depressive disorder without iron deficiency, where treatment of depression was associated with improvement in abnormal craving. [ABSTRACT FROM AUTHOR]

The article discusses the use of long-term repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD), highlighting two case studies of patients who maintained remission through extended rTMS therapy. Topics discussed include the effectiveness of maintenance rTMS, individualized treatment protocols, and the impact of comorbid conditions on therapy outcomes.

In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU Watch List compound was investigated by an internal method that was validated in terms of detection limits, linearities, accuracy, and precision in accordance with quality assurance criteria, and it was used to monitor several rivers from 11 Italian regions. The methodology developed was satisfactorily validated from 5 to 500 ng L−1 for the emerging pollutants studied, and it was applied to different river waters sampled in Italy, revealing the presence of drugs and antibiotics. Rivers were monitored for 2 years by two different campaigns conducted in 2021 and 2022. A total of 19 emerging pollutants were investigated on 45 samples. The most detected analytes were O-desmethylvenlafaxine and venlafaxine. About azole compounds, sulfamethoxazole, fluconazole, and Miconazole were found. About antibiotics, ciprofloxacin and amoxicillin were found in three and one samples, respectively. Moreover, statistical analyses have found a significant correlation between O-desmethylvenlafaxine with venlafaxine, sulfamethoxazole with venlafaxine, and fluconazole with venlafaxine. [ABSTRACT FROM AUTHOR]

The European Union requires environmental monitoring of the antidepressant drug venlafaxine. Advanced oxidation processes provide a remedy against the spread of micropollutants. In this study, the photoinduced and electrochemical decompositions of venlafaxine were investigated in terms of mechanism and efficacy using high-performance liquid chromatography coupled to high-resolution multifragmentation mass spectrometry. Kinetic analysis, structure elucidation, matrix variation, and radical scavenging indicated the dominance of a hydroxyl-mediated indirect mechanism during photodegradation and hydroxyl and direct electrochemical oxidation for electrochemical degradation. Oxidants, sulfate, and chloride ions acted as accelerants, which reduced venlafaxine half-lives from 62 to 25 min. Humic acid decelerated degradation during ultra-violet irradiation up to 50%, but accelerated during electrochemical oxidation up to 56%. In silico quantitative structure activity relationship analysis predicted decreased environmental hazard after advanced oxidation process treatment. In general, photoirradiation proved more efficient due to faster decomposition and slightly less toxic transformation products. Yet, matrix effects would have to be carefully evaluated when potential applications as a fourth purification stage were to be considered. [ABSTRACT FROM AUTHOR]

There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an understanding of whether antidepressants with similar modes of action have consistent negative impacts. Here, we tested the effect of acute exposure to two antidepressants, fluoxetine and venlafaxine (0–50 µg/L), on the behavior of non-target organism, i.e., freshwater pond snail, Lymnaea stagnalis. As compounds interact with chemical cues in the aquatic ecosystems, we also tested whether the effects altered in the presence of bile extract containing 5α-cyprinol sulfate (5α-CPS), a characterized kairomone of a natural predator, common carp (Cyprinus carpio). Behavior was studied using automated tracking and analysis of various locomotion parameters of L. stagnalis. Our results suggest that there are differences in the effects on locomotion upon exposure to venlafaxine and fluoxetine. We found strong evidence for a non-monotonic dose response on venlafaxine exposure, whereas fluoxetine only showed weak evidence of altered locomotion for a specific concentration. Combined exposure to compounds and 5α-CPS reduced the intensity of effects observed in the absence of 5α-CPS, possibly due to reduced bioavailability of the compounds. The results highlight the need for acknowledging different mechanisms of action among antidepressants while investigating their environmental risks. In addition, our results underline the importance of reporting non-significant effects and acknowledging individual variation in behavior for environmental risk assessment. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is therefore desirable to assign a given patient to the most promising individual treatment option as early as possible. We used a polygenic score (PGS) informed electroencephalography (EEG) data-driven approach to identify potential predictors for MDD treatment outcome. Post-hoc we conducted exploratory analyses in order to understand the results in depth. First, an EEG independent component analysis produced 54 functional brain networks in a large heterogeneous cohort of psychiatric patients (n = 4,045; 5–84 yrs.). Next, the network that was associated to PGS for antidepressant-response (PRS-AR) in an independent sample (n = 722) was selected: an age-related posterior alpha network that explained >60 % of EEG variance, and was highly stable over recording time. Translational analyses were performed in two other independent datasets to examine if the network was predictive of psychopharmacotherapy (n = 535) and/or repetitive transcranial magnetic stimulation (rTMS) and concomitant psychotherapy (PT; n = 186) outcome. The network predicted remission to venlafaxine (p = 0.015), resulting in a normalized positive predicted value (nPPV) of 138 %, and rTMS + PT – but in opposite direction for women (p = 0.002) relative to men (p = 0.018) – yielding a nPPV of 131 %. Blinded out-of-sample validations for venlafaxine (n = 29) and rTMS + PT (n = 36) confirmed the findings for venlafaxine, while results for rTMS + PT could not be replicated. These data suggest the existence of a relatively stable EEG posterior alpha aging network related to PGS-AR that has potential as MDD treatment predictor. [ABSTRACT FROM AUTHOR]

In this study, a mixed-matrix method was used to prepare PVDF polymeric membranes with different amounts of TiO2 P25 photocatalyst embedded, which were employed in filtration processes in the presence of UV radiation (LED, peak emission at 375 nm) to eliminate two aqueous micropollutants (MPs) used as model compounds (venlafaxine and metoprolol). The obtained membranes were characterized to gain insights into their texture, morphology, composition, and other catalyst-related properties that could affect the photocatalytic filtration process. For that purpose, N2 adsorption–desorption, contact angle, SEM-EDX, thermal analysis, FTIR, XPS, UV-vis DRS, and PL spectroscopy were used. Filtration tests were carried out in continuous mode using a dead-end filtration cell to evaluate the performance of the prepared membranes in removing the selected MPs. Experiments were performed both in ultrapure water and a secondary effluent from a municipal wastewater treatment plant. It was found that the synthesized membranes could effectively remove the target MPs in ultrapure water, achieving up to 99% elimination. Such process performance decreased drastically in the secondary effluent with removals below 35%. Carbonate/bicarbonate ions in the secondary effluent were identified as the main scavenging substances. Thus, after the partial removal of carbonate/bicarbonate ions from the secondary effluent, the removal of MPs achieved was above 60%. [ABSTRACT FROM AUTHOR]