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Neurotoxicity Research Oct 2022Depression is a leading cause of disability which at its worst leads to suicide. Its treatment relies on psychotherapy in combination with certain antidepressants (AD)...
Prenatal Venlafaxine Exposure-Induced Neurocytoarchitectural and Neuroapoptotic Degeneration in Striatum and Hippocampus of Developing Fetal Brain, Manifesting Long-term Neurocognitive Impairments in Rat Offspring.
Depression is a leading cause of disability which at its worst leads to suicide. Its treatment relies on psychotherapy in combination with certain antidepressants (AD) from various classes such as tricyclics, selective serotonin reuptake inhibitors, or serotonin and norepinephrine reuptake inhibitors (SNRIs). Among SNRIs, venlafaxine (VEN) is one such most commonly prescribed AD which is recently reported to be in the top 50 most prescribed drugs in the USA. Depression during pregnancy is a common condition, where prescribing an AD becomes necessary as untreated depression during pregnancy has its own complications for both mother and the child. This, probably, is why an incredible rise has been reported in prescribing ADs like VEN to pregnant women in the recent past, despite some studies, including the one from our own group, having reported the in-utero VEN-induced apoptotic neurodegeneration in the fetal neocortex and the consequent neurobehavioral anomalies in adulthood. However, there still exists a lack of insight into the effects of intrauterine exposures of VEN on other fetal brain regions like the hippocampus (HPC) and striatum (STR) and the consequent effects on their cognitive and emotional wellbeing in later life. Hence, this study has been conducted where pregnant Charles-Foster (CF) rats were oral gavaged with VEN (25, 40, and 50 mg/kg bw) from gestation day (GD) 05-19. On GD-19, half of the control and treated dams were euthanized to collect their fetuses. Fetal brains were dissected and processed for reactive oxygen species (ROS) estimation neurohistopathology and confocal microscopic studies. The remaining dams were allowed to deliver naturally, and litters were reared for up to 8 weeks then tested for their cognitive abilities by the Morris water maze test and for their emotionality by the Forced swimming test. Our results showed substantial neurocytoarchitectural deficits in both HPC and STR, along with enhanced ROS levels and apoptotic neurodegenerations. Furthermore, VEN-treated young rat offsprings displayed cognitive impairments and depressive behavior as the long-lasting impact of VEN in a dose-dependent manner. So it may be inferred that prenatal VEN-induced oxidative stress causes apoptotic neurodegeneration leading to neuronal loss in HPC and STR which consequently affects the development of the said brain areas resulting in impaired cognitive and emotional abilities of young adult offsprings. Therefore, extrapolating these findings in animal models, caution may be taken before prescribing VEN to pregnant women, especially during the sensitive phase of pregnancy.
Topics: Animals; Female; Hippocampus; Humans; Neocortex; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Reactive Oxygen Species; Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 35819590
DOI: 10.1007/s12640-022-00541-3 -
Clinical Neurology and Neurosurgery Mar 2022Migraine, as a primary headache, is among the leading causes of disability worldwide. The present study aimed at comparing the effects of venlafaxine (VLF) and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Migraine, as a primary headache, is among the leading causes of disability worldwide. The present study aimed at comparing the effects of venlafaxine (VLF) and amitriptyline (AMT) reducing the severity and the number of migraine attacks.
METHODS
Patients with complaints of migraine attacks were randomly divided into two groups. The first group received amitriptyline at a dose of 25 mg every night, and the second group received venlafaxine at a dose of 37.5 mg daily. The duration of treatment was eight weeks.
RESULTS
Eighty patients participated in the current study, out of which 57.5% were females. The mean age of the participants was 33 years, and the mean duration of disease was eight years. Both amitriptyline and venlafaxine significantly reduced the number of attacks per month (AMT: from 10.98 to 2.98, VLF: from 9.98 to 3.18), and six-item Headache Impact Test (HIT-6) score (AMT: from 67.78 to 49.73, VLF: from 66.65 to 48.88), and no significant difference was observed between the two drugs. The results demonstrated no significant relationship between age or disease duration with the score of the HIT-6. The decrease rate in the score of the HIT-6 in males was higher than that of females which shows the modifier role of the gender. Besides, it is noteworthy to mention that the adverse effects of amitriptyline exceeded the venlafaxine among the patients.
CONCLUSION
The effectiveness of AMT and VLF in terms of their potential to reduce the intensity and duration of headaches was more noticeable in male patients than female patients. In terms of adverse drug reactions, patients in the amitriptyline group complained more about adverse drug reactions (ADR) than patients in the venlafaxine group. It seems that in similar conditions, venlafaxine could have priority over amitriptyline in migraine prophylaxis.
Topics: Adult; Amitriptyline; Drug-Related Side Effects and Adverse Reactions; Female; Headache; Humans; Male; Migraine Disorders; Venlafaxine Hydrochloride
PubMed: 35151971
DOI: 10.1016/j.clineuro.2022.107151 -
Chemosphere Jun 2022Venlafaxine (denoted as VFX), a member of the most extensively prescribed antidepressants, is used to handle major depressive disorder, panic disorder and anxiety. This... (Review)
Review
Venlafaxine (denoted as VFX), a member of the most extensively prescribed antidepressants, is used to handle major depressive disorder, panic disorder and anxiety. This medication affects brain chemistry, which could cause an imbalance in depressed people. VFX and its metabolites, on the other hand, are pollutants in the water environment. Through movement and transformation in several procedures like adsorption, photolysis, hydrolysis and biodegradation, they have harmed living creatures, resulting in the enhancement of diverse active chemicals found in the environment. As a result, determining VFX at modest concentrations with excellent sensitivity, specificity and repeatability are critical. To quantify VFX, various analytical methodologies have been developed. Electroanalytical processes, on the other hand, have piqued interest because of their superior benefits over traditional techniques such as speed, sensitivity, directness and affordability. Subsequently, the purpose of this article is to show how to determine VFX electrochemically using a wide range of electrodes, including CPE, GCE, MCE, SPE, PGE and ISE.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Nanostructures; Photolysis; Venlafaxine Hydrochloride
PubMed: 35227745
DOI: 10.1016/j.chemosphere.2022.134116 -
Expert Opinion on Pharmacotherapy 2023Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants... (Review)
Review
Moving from serotonin to serotonin-norepinephrine enhancement with increasing venlafaxine dose: clinical implications and strategies for a successful outcome in major depressive disorder.
INTRODUCTION
Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants are widely accepted as first-line pharmacological treatment for major depressive disorder (MDD), patient response to such treatment is variable, with more than half failing to achieve complete remission, and residual symptoms are frequently present.
AREAS COVERED
Here, the pharmacodynamics of venlafaxine XR are reviewed in relation to its role as both a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine-reuptake inhibitor (SNRI), and we look at how these pharmacodynamic properties can be harnessed to guide clinical practice, asking the question 'is it possible to develop a symptom-cluster-based approach to the treatment of MDD with comorbid anxiety utilizing venlafaxine XR?.' Additionally, three illustrative clinical cases provide practical examples of the utility of venlafaxine-XR in real-world clinical practice. The place of venlafaxine XR in managing fatigue/low energy, a frequent residual symptom in MDD, is explored using pooled data from clinical trials of venlafaxine XR.
EXPERT OPINION
Venlafaxine XR should be considered as a first-line treatment for MDD with or without comorbid anxiety, and there are clear pharmacodynamic signals supporting a symptom cluster-based treatment paradigm for venlafaxine XR.
Topics: Humans; Venlafaxine Hydrochloride; Depressive Disorder, Major; Serotonin; Norepinephrine; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cyclohexanols; Treatment Outcome; Delayed-Action Preparations
PubMed: 37501324
DOI: 10.1080/14656566.2023.2242264 -
Aquatic Toxicology (Amsterdam,... Mar 2022Venlafaxine, a serotonin-noradrenaline reuptake inhibitor, is a widely used antidepressant drug routinely detected in aquatic environments. However, its potential impact...
Venlafaxine, a serotonin-noradrenaline reuptake inhibitor, is a widely used antidepressant drug routinely detected in aquatic environments. However, its potential impact on courtship behaviour in zebrafish is unknown. We tested the hypothesis that venlafaxine disrupts brain monoamine levels and molecular responses essential for courtship behaviour in zebrafish. Zebrafish (Danio rerio) were exposed to venlafaxine (1, 10, and 100 μg/L) for 20 days. We evaluated the molecular levels and neuronal basis of the effect of venlafaxine on courtship behaviour. Here, we show that venlafaxine inhibited courtship behaviour in zebrafish and increased the transcript levels of 5-ht1a and 5-ht2c while decreasing the transcript levels of genes involved in the dopaminergic system, including th1, th2, drd1b, and drd2b. Venlafaxine upregulated 5-HT levels and downregulated dopamine levels. Moreover, the subordinate fish from the venlafaxine-exposed group had significantly lower motor activity than the subordinate fish of the control group. Collectively, our results reveal that venlafaxine can disturb brain monoamine levels, affecting courtship behaviour in adult zebrafish.
Topics: Animals; Antidepressive Agents; Courtship; Dopamine; Serotonin; Venlafaxine Hydrochloride; Water Pollutants, Chemical; Zebrafish
PubMed: 35078056
DOI: 10.1016/j.aquatox.2022.106082 -
Journal of Clinical Psychopharmacology 2020Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc),... (Clinical Trial)
Clinical Trial
PURPOSE/BACKGROUND
Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication.
METHODS/PROCEDURES
In this secondary analysis of a prospective clinical trial, we measured changes in QTc and other electrocardiogram (ECG) parameters in 169 adults 60 years or older with a major depressive disorder treated acutely with venlafaxine extended release up to 300 mg daily. We examined the relationship of venlafaxine dosage and ECG parameters, as well as the relationship between serum levels of venlafaxine and ECG parameters.
FINDINGS/RESULTS
Venlafaxine exposure was not associated with an increase in QTc. Heart rate increased with venlafaxine treatment, whereas the PR interval shortened, and QRS width did not change significantly. The QTc change from baseline was not associated with venlafaxine dosages or serum concentrations. Age, sex, cardiovascular comorbidities, and depression remission status did not predict changes in QTc with venlafaxine.
IMPLICATIONS/CONCLUSIONS
Venlafaxine treatment did not prolong QTc or other ECG parameters, even in high dosages in older depressed adults. These findings indicate that venlafaxine does not significantly affect cardiac conduction in most older patients.
Topics: Action Potentials; Age Factors; Aged; Aged, 80 and over; Depressive Disorder, Major; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; North America; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 33044352
DOI: 10.1097/JCP.0000000000001287 -
Journal of Integrative Neuroscience Jul 2023Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to...
BACKGROUND
Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to improve antioxidant activity and improves liver damage. This study evaluates malic acid anti-depressant activity in the hypothalamus of stressed rats.
METHODS
Thirty-six male albino rats were divided into 2 equal groups; Normal and chronic mild stress (CMS) rats. Normal rats were divided into 3 equal groups; control, malic acid, and venlafaxine drug groups: normal rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. CMS rats were divided into 3 equal groups; CMS, CMS + malic acid, and CMS + venlafaxine drug: CMS rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. All the above-mentioned treatments were administered once a day by oral gavage for 6 weeks.
RESULTS
The obtained results revealed that the animal behavioral tests such as forced swimming test, tail suspension test, sucrose preference test, and open-field test (center square entries test, center square duration test, and distance travelled test), norepinephrine, dopamine, serotonin, γ-aminobutyric acid, nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity, oxidative index, conjugated dienes, catalase, glutathione peroxidase, superoxide dismutase, malondialdehyde, interleukin-6, tumor necrosis factor-α, interleukin-10, interleukin-1β, sodium/potassium-ATPase activity, and histamine-N-methyl transferase () and tyrosine hydroxylase () enzymes in the hypothalamus of stressed rats, were returned to approaching the normal state in the stressed group after treating with malic acid for 6 weeks.
CONCLUSIONS
Malic acid ameliorated stressed-related symptoms and it inhibited superoxide anion and neuro-inflammation in the hypothalamus of stressed rats.
Topics: Rats; Male; Animals; Venlafaxine Hydrochloride; Saline Solution; Depression; Hypothalamus; Stress, Psychological; Oxidative Stress
PubMed: 37519180
DOI: 10.31083/j.jin2204098 -
Comparative Biochemistry and... Jul 2023Venlafaxine (VFX), a commonly prescribed antidepressant often detected in wastewater effluent, and acute temperature elevations from climate change and increased...
Venlafaxine (VFX), a commonly prescribed antidepressant often detected in wastewater effluent, and acute temperature elevations from climate change and increased urbanization, are two environmental stressors currently placing freshwater ecosystems at risk. This study focused on understanding if exposure to VFX impacts the agitation temperature (T) and critical thermal maximum (CT) of zebrafish (Danio rerio). Additionally, we examined the interactive effects of VFX and acute thermal stress on zebrafish heat shock and inflammatory immune responses. A 96 h 1.0 μg/L VFX exposure experiment was conducted, followed by assessment of thermal tolerance via CT challenge. Heat shock proteins and pro-inflammatory immune cytokines were quantified through gene expression analysis by quantitative PCR (qPCR) on hsp 70, hsp 90, hsp 47, il-8, tnfα, and il-1β within gill and liver tissue. No significant changes in agitation temperature between control and exposed fish were observed, nor were there any differences in CT based on treatment. Unsurprisingly, hsp 47, 70, and 90 were all upregulated in groups exposed solely to CT, while only hsp 47 within gill tissue showed signs of interactive effects, which was significantly decreased in fish exposed to both VFX and CT. No induction of an inflammatory response occurred. This study demonstrated that environmentally relevant concentrations of VFX have no impact on thermal tolerance performance in zebrafish. However, VFX can cause diminished function of protective heat shock mechanisms, which could be detrimental to freshwater fish populations and aquatic ecosystems as temperature spikes become more frequent from climate change and urbanization near watersheds.
Topics: Animals; Zebrafish; Venlafaxine Hydrochloride; Ecosystem; Heat-Shock Response; Antidepressive Agents
PubMed: 37004898
DOI: 10.1016/j.cbpc.2023.109620 -
International Clinical... Sep 2019The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations...
OBJECTIVE
The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations of polypharmacy is invaluable. This study is to uncover the potential of pharmacokinetic interactions between venlafaxine and trimipramine in a naturalistic sample.
METHODS
Out of a therapeutic drug monitoring database with plasma concentrations of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV), we considered two groups of patients receiving venlafaxine without known cytochrome P450 confounding medications, taking solely venlafaxine: V0 (n = 905), and a group of patients co-medicated with trimipramine, VTRIM (n = 33). For VEN, ODV and active moiety (sum of VEN + ODV) plasma concentrations and dose-adjusted concentrations as well as ODV/VEN ratios were compared between groups using the Mann-Whitney U test with a significance level of 0.05.
RESULTS
Patients co-medicated with trimipramine had higher plasma concentrations of VEN (183.0 vs. 72.0, +154%, P = 0.002) and AM (324.0 vs. 267.5, +21%, P = 0.005) and higher dose adjusted plasma concentrations than patients in the control group (P = 0.001 and P = 0.003). No differences were found for ODV and C/D ODV (P < 0.05 for both comparisons). The metabolite to parent ratio, ODV/VEN, was significantly lower in the VTRIM group (1.15 vs. 2.37, P = 0.012).
CONCLUSION
Findings suggest inhibitory effects of trimipramine on venlafaxine pharmacokinetics most likely via an inhibition of CYP 2D6 or by saturated enzyme capacity. The lack of in vitro data hampers the understanding of the exact mechanisms. Clinicians should be aware of drug-drug interactions when combining these agents. Therapeutic drug monitoring helps to ensure treatment efficacy and patients' safety.
Topics: Adult; Desvenlafaxine Succinate; Female; Humans; Male; Middle Aged; Trimipramine; Venlafaxine Hydrochloride
PubMed: 31094902
DOI: 10.1097/YIC.0000000000000268 -
Cells Jun 2021The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in...
The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic parameters and markers involved in the regulation of synaptic plasticity and cell damage in an animal model of coexisting depression and hypothyroidism, namely, Wistar Kyoto rats treated with propylthiouracil. In this model, in relation to the depression model itself, the glycolysis process in the brain was weakened, and a reduction in pyruvate dehydrogenase in the frontal cortex was normalized only by the combined treatment with L-thyroxine and venlafaxine, whereas changes in pyruvate and lactate levels were affected by all applied therapies. None of the drugs improved the decrease in the expression of mitochondrial respiratory chain enzymes. No intensification of glucocorticoid action was shown, while an unfavorable change caused by the lack of thyroid hormones was an increase in the caspase-1 level, which was not reversed by venlafaxine alone. The results indicated that the combined administration of drugs was more effective in normalizing glycolysis and the transition to the Krebs cycle than the use of venlafaxine or L-thyroxine alone.
Topics: Animals; Depression; Disease Models, Animal; Drug Therapy, Combination; Frontal Lobe; Humans; Hypothyroidism; Male; Neuronal Plasticity; Rats; Rats, Inbred WKY; Thyroxine; Venlafaxine Hydrochloride
PubMed: 34198731
DOI: 10.3390/cells10061394