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Aquatic Toxicology (Amsterdam,... Jan 2022Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a highly prescribed antidepressant and is detected at µg/L concentrations in waterways...
Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a highly prescribed antidepressant and is detected at µg/L concentrations in waterways receiving municipal wastewater effluents. We previously showed that early-life venlafaxine exposure disrupted the normal development of the nervous system and reduces larval activity in zebrafish (Danio rerio). However, it is unclear whether the reduced swimming activity may be associated with impaired cardiac function. Here we tested the hypothesis that zygotic exposure to venlafaxine impacts the development and function of the larval zebrafish heart. Venlafaxine (0, 1 or 10 ng) was administered by microinjection into freshly fertilized zebrafish embryos (1-4 cell stage) to assess heart development and function during early-life stages. Venlafaxine deposition in the zygote led to precocious development of the embryo heart, including the timing of the first heartbeat, increased heart size, and a higher heart rate at 24- and 48-hours post-fertilization (hpf). Also, waterborne exposure to environmental levels of this antidepressant during early development increased the heart rate at 48 hpf of zebrafish larvae mimicking the zygotic deposition. The venlafaxine-induced higher heart rate in the embryos was abolished in the presence of NAN-190, an antagonist of the 5HT receptor. Also, heart rate dropped below control levels in the 10 ng, but not 1 ng venlafaxine group at 72 and 96 hpf. An acute stressor reduced the venlafaxine-induced heart rate at 48 hpf but did not affect the already reduced heart rate at 72 and 96 hpf in the 10 ng venlafaxine group. Our results suggest that the higher heart rate in the venlafaxine group may be due to an enhanced serotonin stimulation of the 5HT receptor. Taken together, early-life venlafaxine exposure disrupts cardiac development and has the potential to compromise the cardiovascular performance of larval zebrafish.
Topics: Animals; Antidepressive Agents; Embryo, Nonmammalian; Heart; Larva; Venlafaxine Hydrochloride; Water Pollutants, Chemical; Zebrafish
PubMed: 34856460
DOI: 10.1016/j.aquatox.2021.106041 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2021
Topics: Antipsychotic Agents; Cardiotoxicity; Cyclohexanols; Dibenzothiazepines; Drug Overdose; Humans; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 33871300
DOI: 10.1080/15563650.2021.1914341 -
Neuroscience and Biobehavioral Reviews May 2023Studies explicitly reporting data concerning the evaluation of the effect of antidepressants on the periodic leg movements during sleep (PLMS) index obtained by... (Meta-Analysis)
Meta-Analysis Review
Studies explicitly reporting data concerning the evaluation of the effect of antidepressants on the periodic leg movements during sleep (PLMS) index obtained by polysomnography were reviewed and selected. A random-effects model meta-analysis was carried out. The level of evidence was also assessed for each paper. Twelve studies were included in the final meta-analysis, seven interventional and five observational. Most studies were characterized by Level III evidence (non-randomized controlled trials), with the exception of four studies, which were classified as Level IV (case series, case-control, or historically controlled studies). Selective serotonin reuptake inhibitors (SSRIs) were used in seven studies. The analysis of the assessments involving SSRIs or venlafaxine showed an overall large effect size, clearly much larger than that obtained with studies using other antidepressants. Heterogeneity was substantial. This meta-analysis confirms the previous reports on the increase in PLMS often associated with the use of SSRIs (and venlafaxine); however, the absent or smaller effect of the other categories of antidepressants needs to be confirmed by more numerous and better controlled studies.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Leg; Antidepressive Agents; Sleep
PubMed: 36914081
DOI: 10.1016/j.neubiorev.2023.105126 -
Life Sciences May 2023The current work aims to demonstrate the potential defensive function of venlafaxine (VLF) in cardiotoxicity and nephrotoxicity caused by cisplatin (CP), that could be...
AIM
The current work aims to demonstrate the potential defensive function of venlafaxine (VLF) in cardiotoxicity and nephrotoxicity caused by cisplatin (CP), that could be by modulating extracellular signal-regulated kinase (ERK)1/2 and nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase NOX4 pathways.
MAIN METHODS
Five groups of rats were used, as follow: three control groups (control, carboxymethyl cellulose, and VLF), CP group got CP once (7 mg/kg, intraperitoneally, i.p.), and (CP+ VLF) group got CP once then after 1 h they got VLF {50 mg/kg daily, orally for 14 days}. At the end of the study; electrocardiogram (ECG) was recorded for anaesthized rats then blood samples and tissues were taken for biochemical and histopathological investigations. Caspase 3, a marker of cellular damage and apoptosis was detected by immunohistochemistry.
KEY FINDINGS
CP treatment significantly impaired cardiac functions as evidenced by changes in rats' ECG. Cardiac enzymes, renal markers and inflammatory markers were increased with decreased activities of the total antioxidant capacity, superoxide dismutase and glutathione peroxidase. Also, ERK1/2 and NOX4 were upregulated with histopathological and immunohistochemical alterations of heart and kidney. While, VLF markedly alleviated CP-induced functional cardiac abnormalities and improved ECG pattern. It reduced both cardiac and renal biomarkers, oxidative stress, proinflammatory cytokine with ERK1/2 and NOX4 downregulation, improved the histopathological and immunohistochemical changes induced by cisplatin in heart and kidney.
SIGNIFICANCE
VLF treatment impedes cardiotoxicity and nephrotoxicity caused by CP. This beneficial effect was mediated through reduction of oxidative stress, inflammation, and apoptosis by targeting the ERK1/2 and NOX4.
Topics: Rats; Animals; Cisplatin; Venlafaxine Hydrochloride; Cardiotoxicity; Kidney; Antioxidants; Oxidative Stress; Apoptosis; Antineoplastic Agents
PubMed: 36898429
DOI: 10.1016/j.lfs.2023.121561 -
Birth Defects Research Aug 2021Some studies have reported associations between prenatal use of venlafaxine, a serotonin-norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and...
BACKGROUND
Some studies have reported associations between prenatal use of venlafaxine, a serotonin-norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and some birth defects. We described the prevalence of venlafaxine prescription claims among privately insured women of reproductive age and pregnant women.
METHODS
Venlafaxine prescription claims were examined using the IBM MarketScan Commercial Databases. We included women of reproductive age (15-44 years) who had ≤45 days of lapsed enrollment during the calendar year of interest (2011-2016) in a non-capitated healthcare plan sponsored by a large, self-insured employer with prescription drug coverage and no mental health service carve-out. Annual cohorts of pregnant women were identified among eligible women of reproductive age via pregnancy diagnosis and procedure codes. Venlafaxine prescriptions were identified via National Drug Codes in outpatient pharmacy claims and we estimated the annual proportion of women with venlafaxine claims by pregnancy trimester (pregnant women only), age, and Census division.
RESULTS
Each year during 2011-2016, approximately 1.2% of eligible reproductive-aged and 0.3% of eligible pregnant women filled a venlafaxine prescription. Among pregnant women, the proportion with venlafaxine claims was highest during the first trimester and decreased during the second and third trimesters. Small temporal increases in venlafaxine claims were observed for reproductive-aged and pregnant women, with the largest among women aged 15-19 years.
CONCLUSIONS
Venlafaxine prescription claims were low among women of reproductive age and pregnant women during 2011-2016, with some increasing use over time among women aged 15-19 years.
Topics: Adolescent; Adult; Female; Humans; Pregnancy; Pregnant Women; Prescription Drugs; Prescriptions; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 33860984
DOI: 10.1002/bdr2.1897 -
Brazilian Journal of Biology = Revista... 2021The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse....
The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.
Topics: Animals; Antineoplastic Agents; DNA Damage; Dose-Response Relationship, Drug; Erythrocytes; Mice; Micronucleus Tests; Venlafaxine Hydrochloride
PubMed: 34932628
DOI: 10.1590/1519-6984.251289 -
Journal of Psychopharmacology (Oxford,... Apr 2023Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and...
BACKGROUND
Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed.
AIMS
To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if and genetic variation plays a role.
METHODS
Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. and metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates.
RESULTS
Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, = 0.007) and lower triglycerides (-0.17 mmol/L, 95% CI: -0.29 to -0.05, = 0.007), compared to normal metabolisers.
CONCLUSIONS
Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline.
Topics: Female; Male; Animals; Cytochrome P-450 CYP2D6; Sertraline; Antipsychotic Agents; Venlafaxine Hydrochloride; Cytochrome P-450 CYP2C19; Antidepressive Agents; Triglycerides; Cholesterol; United Kingdom
PubMed: 36772859
DOI: 10.1177/02698811231152748 -
Environmental Pollution (Barking, Essex... Apr 2022The beta-blocker atenolol (ATE), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are frequently detected in municipal wastewater...
The beta-blocker atenolol (ATE), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are frequently detected in municipal wastewater effluents, but little is known about their ecotoxicological effect on aquatic animals. Herein, ATE and VEN were selected to explore their accumulation and global DNA methylation (GDM) in zebrafish tissues after a 30-day exposure. Molecular dynamics (MD) stimulation was used to investigate the toxic mechanism of ATE and VEN exposure. The results demonstrated that ATE and VEN could reduce the condition factor of zebrafish. The bioaccumulation capacity for ATE and VEN was in the order of liver > gut > gill > brain and liver > gut > brain > gill, respectively. After a 30-day recovery, ATE and VEN could still be detected in zebrafish tissues when exposure concentrations were ≥10 μg/L. Moreover, ATE and VEN induced global DNA hypomethylation in different tissues with a dose-dependent manner and their main target tissues were liver and brain. When the exposure concentrations of ATE and VEN were increased to 100 μg/L, the global DNA hypomethylation of liver and brain were reduced to 27% and 18%, respectively. In the same tissue exposed to the same concentration, DNA hypomethylation induced by VEN was more serious than that of ATE. After a 30-day recovery, the global DNA hypomethylations caused by the two drugs were still persistent, and the recovery of VEN was slower than that of ATE. The MD simulation results showed that both ATE and VEN could reduce the catalytic activity of DNA Methyltransferase 1 (DNMT1), while the effect of VEN on the 3D conformational changes of the DNMT1 domain was more significant, resulting in a lower DNA methylation rate. The current study shed new light on the toxic mechanism and potential adverse impacts of ATE and VEN on zebrafish, providing essential information to the further ecotoxicological risk assessment of these drugs in the aquatic environment.
Topics: Animals; Atenolol; Bioaccumulation; DNA; DNA Methylation; Venlafaxine Hydrochloride; Zebrafish
PubMed: 35081461
DOI: 10.1016/j.envpol.2022.118898 -
The Science of the Total Environment Nov 2022Ozonation has been used to effectively remove micropollutants from the secondary effluent in several wastewater treatment plants. It is known that ozonation transforms...
Ozonation has been used to effectively remove micropollutants from the secondary effluent in several wastewater treatment plants. It is known that ozonation transforms tertiary amine compounds into their respective N-oxides, however in an earlier study a mass balance could not be closed at elevated ozone concentrations, leading to the assumption that more ozonation products are possible. This study was conducted to elucidate which (hitherto unknown) ozonation products can be formed from venlafaxine and tramadol when ozonating wastewater. Ozonation experiments were performed with tramadol and venlafaxine N-oxide in two different set-ups. Both tramadol- and venlafaxine N-oxide degraded during ozonation in pure (deionized) water in both semi-continuous and batch mode ozonation set-ups. 13 and 17 new transformation products were detected from tramadol- and venlafaxine N-oxide respectively, using high resolution mass spectrometry with ESI(+) ionization. Empirical chemical formulas were proposed based on the determination of the exact masses and interpretation of the product ion spectra. These transformation products result from the addition of one to three oxygen atoms and removal of C, -CH, CH, CH, etc., from the parent molecule, respectively. Quenching experiments suggested that most of the transformation products originated from the direct reaction with ozone (eight for tramadol N-oxide and ten for venlafaxine N-oxide), whereas fewer products originated from the reaction with OH radicals (three for tramadol N-oxide and three for venlafaxine N-oxide). Reaction mechanisms and chemical structures of products are proposed, based on the available active sites and past literature on ozone reaction mechanisms. The experimental results are compared to theory and literature on ozone reactive sites and ozone reaction mechanisms. All in all this shows that there can be multiple ozonation products, and ozonation pathways can be complex, even if initially only one ozonation product is formed.
Topics: Organic Chemicals; Oxides; Ozone; Tramadol; Venlafaxine Hydrochloride; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 35817117
DOI: 10.1016/j.scitotenv.2022.157259 -
European Archives of Psychiatry and... Oct 2019To address the potential correlation between plasma concentrations of venlafaxine (VEN), its active metabolite O-desmethylvenlafaxine (ODVEN) and the active moiety, AM,...
To address the potential correlation between plasma concentrations of venlafaxine (VEN), its active metabolite O-desmethylvenlafaxine (ODVEN) and the active moiety, AM, (ODVEN + VEN) and adverse drug reactions (ADR) in a large naturalistic sample of in- and outpatients. We compared plasma concentrations of VEN, ODVEN and AM and dose-adjusted (C/D) levels as well the ODVEN/VEN ratios between patients complaining ADRs, following the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 114) and patients without ADRs (control group, n = 688) out of a naturalistic database. We also investigated potential pharmacokinetic correlates of the four UKU categories by comparing patients complaining ADRs with those who did not. Based on previous literature we applied different ODVEN/VEN ratio values as cut-offs to split our sample into two groups at a time and compare frequencies of ADRs between the groups. No differences for demographic and pharmacokinetic variables including plasma and C/D concentrations as well as ODVEN/VEN ratios were observed between study groups. Neither the comparisons between females and males nor between elderly and non-elderly patients revealed significant differences (p > 0.05 in all cases). No differences were also reported exploring the patients complaining ADRs from the 4 UKU categories separately. After applying various ODVEN/VEN cut-offs, groups did not display differences in frequencies of ADRs (p > 0.05 in all cases). Our findings do not demonstrate a direct link between venlafaxine metabolism measures and ADRs. Therefore, additional dimensions are needed to be considered in future trials aiming to disentangle the involved aspects of ADRs in patients receiving venlafaxine.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Databases, Factual; Desvenlafaxine Succinate; Drug-Related Side Effects and Adverse Reactions; Female; Germany; Humans; Male; Middle Aged; Mood Disorders; Venlafaxine Hydrochloride; Young Adult
PubMed: 30923938
DOI: 10.1007/s00406-019-01005-0