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Clinical Epigenetics Dec 2022BDNF exon IV promoter methylation is a potential biomarker for treatment response to antidepressants in MDD. We have previously shown CpG-87 methylation as a successful...
BACKGROUND
BDNF exon IV promoter methylation is a potential biomarker for treatment response to antidepressants in MDD. We have previously shown CpG-87 methylation as a successful biomarker for the prediction of non-response to monoaminergic antidepressants like the SSRI Fluoxetine or the SNRI Venlafaxine. This study aimed to dissect the biological evidence and mechanisms for the functionality of CpG-87 methylation in a cell culture model.
RESULTS
We observed a significant interaction between methylation and antidepressant-mediated transcriptional activity in BDNF exon IV promoter. In addition, antidepressant treatment increased the promoter methylation in a concentration-dependent manner. Further single CpG methylation of -87 did not change the promoter activity, but methylation of CREB domain CpG-39 increased the transcriptional activity in an antidepressant-dependent manner. Interestingly, DNMT3a overexpression also increases the BDNF exon IV transcription and more so in Venlafaxine-treated cells.
CONCLUSIONS
The study strengthens the previously reported association between antidepressant treatment and BDNF exon IV promoter methylation as well as hints toward the mechanism of action. We argue that potential CpG methylation biomarkers display a complex synergy with the molecular changes at the neighboring CpG positions, thus highlighting the importance of epiallele analyses.
Topics: Humans; Brain-Derived Neurotrophic Factor; Venlafaxine Hydrochloride; DNA Methylation; Antidepressive Agents; Exons
PubMed: 36572893
DOI: 10.1186/s13148-022-01415-3 -
Neurology India 2022Post stroke depression (PSD) is an under diagnosed morbidity of stroke and can negatively affect the prognosis of the patient. (Observational Study)
Observational Study
CONTEXT
Post stroke depression (PSD) is an under diagnosed morbidity of stroke and can negatively affect the prognosis of the patient.
AIMS
We intended to study the prevalence of PSD and the commonly used anti-depressants and their outcome in patients with PSD.
SETTINGS AND DESIGN
A prospective observational study was conducted in the patients admitted to the stroke unit of a tertiary care centre.
METHODS AND MATERIALS
Diagnosis of post stroke depression was made by the Hamilton Depression Rating Scale (HDRS) during the two-week period after stroke or in the clinic follow up. A comparison of clinical outcome and adverse events of the two anti-depressants used, i.e. venlafaxine and fluoxetine were done by a follow up of up to 6 months.
STATISTICAL ANALYSIS USED
Independent sample test was used for statistical purposes in the study.
RESULTS
Out of the 326 stroke patients admitted in the department, 73 had PSD and 60 patients out of this were assigned into the study. Forty patients were males, and the mean age of the sample population was found to be 62.13 ± 11.14. Major risk factors identified were hypertension, diabetes mellitus, and dyslipidemia. Venlafaxine showed better outcome and less adverse events compared to fluoxetine. Major adverse events observed were hyponatremia, headache, insomnia, and anxiety.
CONCLUSIONS
PSD in the early phase affects a substantial number of the stroke patients. Venlafaxine has got a better outcome and adverse event profile compared to fluoxetine in this group of patients. However, larger multicenter studies will provide more helpful data in this area.
Topics: Male; Humans; Female; Venlafaxine Hydrochloride; Fluoxetine; Depression; Cyclohexanols; Stroke
PubMed: 36537424
DOI: 10.4103/0028-3886.364069 -
Environmental Science and Pollution... Feb 2023Psychiatric drugs released by humans in wastewater have received more attention because of their potential risks for aquatic organisms. In this study, the occurrence of...
Psychiatric drugs released by humans in wastewater have received more attention because of their potential risks for aquatic organisms. In this study, the occurrence of the two most common groups of psychiatric drugs (sedatives-hypnotics-anxiolytics and antidepressants) were evaluated in the Tehran South Municipal Wastewater Treatment Plant. All the target sedatives-hypnotics-anxiolytics (alprazolam, phenobarbital, and thioridazine) and antidepressants (fluoxetine, citalopram, sertraline, and venlafaxine) were observed in influent and secondary clarification (SC) effluent. Thioridazine (164.25 ± 218.74 ng/L) and citalopram (672.53 ± 938.56 ng/L) had the highest mean concentrations in the influent, while alprazolam (5.09 ± 2.33 ng/L) and citalopram (776.97 ± 1088.01 ng/L) had the highest concentrations in the SC effluent. The higher concentrations of the psychiatric drugs, except thioridazine, were detected in the SC effluent compared to the concentrations in the influent. The increased drugs concentrations, with negative removal efficiencies, were more distinctive in the cold season samples. Psychiatric drugs processed in the chlorination unit followed a completely different pattern compared to the drugs in the biological treatment unit. All the drugs' concentrations, except thioridazine, decreased in the chlorination unit, ranging between 27 ± 14% for alprazolam and 75 ± 10% for citalopram. However, the mean concentrations of the detected drugs were as follows: sertraline (11.96 ± 11.62 ng/L) and venlafaxine (184.94 ± 219.74 ng/L) which could cause environmental and ecological concerns.
Topics: Humans; Water Pollutants, Chemical; Citalopram; Sertraline; Venlafaxine Hydrochloride; Thioridazine; Anti-Anxiety Agents; Alprazolam; Iran; Antidepressive Agents; Pharmaceutical Preparations; Water Purification; Hypnotics and Sedatives; Environmental Monitoring; Waste Disposal, Fluid
PubMed: 36374381
DOI: 10.1007/s11356-022-23667-5 -
Scientific Reports Oct 2022Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers...
Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers (NFs) for buccal delivery of VEN to avoid the hepatic metabolism and enzymatic degradation in the GIT and develop an effective control of drug release. The optimized NFs were obtained by blending polylactic acid (PLA), and poly (ɛ-caprolactone) (PCL) fixed at a ratio of 1:1. It was characterized for morphology, drug-loading, FTIR, XRD, DSC, and in vitro drug release. Ex vivo permeability of the blend NFs was assessed using chicken pouch mucosa compared to VEN suspension, followed by histopathological examination. Further, the cytotoxic effect in three different cell lines using WST-1 assay. SEM morphologies refer to defect-free uniform NFs of PLA, PCL, and PLA/PCL mats. These fibers had a diameter ranging from 200 to 500 nm. The physico-thermal characterization of NFs depicted that the drug was successfully loaded and in an amorphous state in the PLA/PCL NFs. In vitro release of NFs substantiated a bi-phasic profile with an initial burst release of about 30% in the initial 0.5 h and a prolonged cumulative release pattern that reached 80% over 96 h following a non-Fickian diffusion mechanism. Ex vivo permeation emphasizes the major enhancement of the sustained drug release and the noticeable decrease in the permeability of the drug from NFs. Cytotoxicity data found that IC of VEN alone was 217.55 μg/mL, then VEN-NFs recorded an IC value of 250.62 μg/mL, and plain NFs showed the lowest toxicity and IC 440.48 μg/mL in oral epithelial cells (OEC). Histopathology and cell toxicity studies demonstrated the preserved mucosal architecture and the preclinical safety. The developed PLA/PCL NFs can be promising drug carriers to introduce a step-change in improved psychiatric treatment healthcare.
Topics: Nanofibers; Polymers; Venlafaxine Hydrochloride; Delayed-Action Preparations; Polyesters
PubMed: 36302929
DOI: 10.1038/s41598-022-22878-7 -
Arquivos de Neuro-psiquiatria Sep 2022Migraine affects 1 billion people worldwide and > 30 million Brazilians; besides, it is an underdiagnosed and undertreated disorder.
BACKGROUND
Migraine affects 1 billion people worldwide and > 30 million Brazilians; besides, it is an underdiagnosed and undertreated disorder.
OBJECTIVE
The need to disseminate knowledge about the prophylactic treatment of migraine is known, so the Brazilian Headache Society (SBCe, in the Portuguese acronym) appointed a committee of authors with the objective of establishing a consensus with recommendations on the prophylactic treatment of episodic migraine based on articles from the world literature as well as from personal experience.
METHODS
Meetings were held entirely online, with the participation of 12 groups that reviewed and wrote about the pharmacological categories of drugs and, at the end, met to read and finish the document. The drug classes studied in part II of this Consensus were: antihypertensives, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, calcium channel blockers, other drugs, and rational polytherapy.
RESULTS
From this list of drugs, only candesartan has been established as effective in controlling episodic migraine. Flunarizine, venlafaxine, duloxetine, and pizotifen were defined as likely to be effective, while lisinopril, enalapril, escitalopram, fluvoxamine, quetiapine, atorvastatin, simvastatin, cyproheptadine, and melatonin were possibly effective in prophylaxis of the disease.
CONCLUSIONS
Despite an effort by the scientific community to find really effective drugs in the treatment of migraine, given the large number of drugs tested for this purpose, we still have few therapeutic options.
Topics: Humans; Brazil; Consensus; Migraine Disorders; Venlafaxine Hydrochloride; Headache
PubMed: 36257618
DOI: 10.1055/s-0042-1755320 -
Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
International Journal of Molecular... Sep 2022Drug metabolizing enzyme activity is affected by various factors such as drug-drug interactions, and a method to quantify drug metabolizing enzyme activity in real time...
Drug metabolizing enzyme activity is affected by various factors such as drug-drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled -desmethylvenlafaxine (I-ODV) was obtained with high labeling and purity, and its metabolism was found to strongly involve CYP3A4 and CYP2D6. SPECT imaging in normal mice showed that the administered I-ODV accumulated early in the liver and was excreted into the gallbladder, as evaluated by time activity curves. In its biological distribution, I-ODV administered to mice accumulated early in the liver, and only the metabolite of I-ODV was quickly excreted into the bile. In CYP3A4- and CYP2D6-inhibited model mice, the accumulation in bile decreased more than in normal mice, indicating inhibition of metabolite production. These results indicated that imaging and quantifying the accumulation of radioactive metabolites in excretory organs will aid in determining the dosages of various drugs metabolized by CYP3A4 and CYP2D6 for individualized medicine. Thus, I-ODV has the potential to direct, comprehensive detection and measurement of hepatic CYP3A4 and CYP2D6 activity by a simple and less invasive approach.
Topics: Animals; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Desvenlafaxine Succinate; Iodine Radioisotopes; Liver; Mice; Radiopharmaceuticals; Venlafaxine Hydrochloride
PubMed: 36232758
DOI: 10.3390/ijms231911458 -
BMC Medical Informatics and Decision... Oct 2022Dementia is a group of symptoms that largely affects older people. The majority of patients face behavioural and psychological symptoms (BPSD) during the course of their...
BACKGROUND
Dementia is a group of symptoms that largely affects older people. The majority of patients face behavioural and psychological symptoms (BPSD) during the course of their illness. Alzheimer's disease (AD) and vascular dementia (VaD) are two of the most prevalent types of dementia. Available medications provide symptomatic benefits and provide relief from BPSD and associated health issues. However, it is unclear how specific dementia, antidepressant, antipsychotic, antianxiety, and mood stabiliser drugs, used in the treatment of depression and dementia subtypes are prescribed in hospital admission, during hospital stay, and at the time of discharge. To address this, we apply multi-dimensional data analytical approaches to understand drug prescribing practices within hospitals in England and Wales.
METHODS
We made use of the UK National Audit of Dementia (NAD) dataset and pre-processed the dataset. We evaluated the pairwise Pearson correlation of the dataset and selected key data features which are highly correlated with dementia subtypes. After that, we selected drug prescribing behaviours (e.g. specific medications at the time of admission, during the hospital stay, and upon discharge), drugs and disorders. Then to shed light on the relations across multiple features or dimensions, we carried out multiple regression analyses, considering the number of dementia, antidepressant, antipsychotic, antianxiety, mood stabiliser, and antiepileptic/anticonvulsant drug prescriptions as dependent variables, and the prescription of other drugs, number of patients with dementia subtypes (AD/VaD), and depression as independent variables.
RESULTS
In terms of antidepressant drugs prescribed in hospital admission, during stay and discharge, the number of sertraline and venlafaxine prescriptions were associated with the number of VaD patients whilst the number of mirtazapine prescriptions was associated with frontotemporal dementia patients. During admission, the number of lamotrigine prescriptions was associated with frontotemporal dementia patients, and with the number of valproate and dosulepin prescriptions. During discharge, the number of mirtazapine prescriptions was associated with the number of donepezil prescriptions in conjunction with frontotemporal dementia patients. Finally, the number of prescriptions of donepezil/memantine at admission, during hospital stay and at discharge exhibited positive association with AD patients.
CONCLUSION
Our analyses reveal a complex, multifaceted set of interactions among prescribed drug types, dementia subtypes, and depression.
Topics: Aged; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Depression; Donepezil; Dothiepin; Frontotemporal Dementia; Hospitals; Humans; Lamotrigine; Memantine; Mirtazapine; NAD; Sertraline; Valproic Acid; Venlafaxine Hydrochloride; Wales
PubMed: 36207697
DOI: 10.1186/s12911-022-01892-9 -
PloS One 2022Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients.
METHODS
A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ).
RESULTS
Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.763; 95% CI: 0.602-0.966, I2: 0.0).
FINDINGS
Most evidence supports that the use of antidepressant medications, mainly Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with SARS-CoV-2. Some studies showed contradictory findings regarding the effects of antidepressants on the severity of COVID-19. Further clinical trials should be conducted to clarify the effects of antidepressants on the severity of COVID-19.
Topics: Antidepressive Agents; Fluoxetine; Fluvoxamine; Humans; Norepinephrine; Paroxetine; SARS-CoV-2; Serotonin; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; COVID-19 Drug Treatment
PubMed: 36201406
DOI: 10.1371/journal.pone.0267423 -
The Journal of International Medical... Sep 2022Painful post-traumatic trigeminal neuropathy (PPTTN) can result from iatrogenic injury to one or more branches of the trigeminal nerve during oral surgical procedures...
Painful post-traumatic trigeminal neuropathy (PPTTN) can result from iatrogenic injury to one or more branches of the trigeminal nerve during oral surgical procedures such as tooth extractions. Like other chronic neuropathic pain conditions, PPTTN can significantly alter the patient's quality of life, especially when pharmacological treatment is ineffective or not tolerated. As such, new treatment options have been investigated, including local injections of botulinum toxin type A (BTX-A). A 29-year-old woman presented to our tertiary orofacial pain clinic for evaluation of chronic electric shock-like pain attacks and severe allodynia in the territory of the right inferior alveolar nerve and buccal nerve following right mandibular third molar extraction 3 years prior. Following several failed attempts at classic pharmacological management (including carbamazepine, venlafaxine, duloxetine, pregabalin, clonazepam, and amitriptyline), BTX-A injections were administered in the vicinity of the right mental nerve. This treatment provided significant improvement in the patient's condition and overall quality of life with no significant adverse effects. Because both neuropathies were significantly improved by remote BTX-A injections, this case report provides preliminary clinical evidence supporting spinopetal transport of BTX-A, as shown in animal models, as an underlying pathophysiological mechanism of BTX-A-mediated analgesia.
Topics: Amitriptyline; Animals; Botulinum Toxins, Type A; Carbamazepine; Clonazepam; Duloxetine Hydrochloride; Humans; Mandibular Nerve; Neuralgia; Pregabalin; Quality of Life; Venlafaxine Hydrochloride
PubMed: 36172992
DOI: 10.1177/03000605211047704