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Psychopharmacology Bulletin Aug 2023A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed...
OBJECTIVES
A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed to address the effects of venlafaxine use during pregnancy on the development of the brain in mice.
EXPERIMENTAL DESIGN
Fourteen female BALB/c mice were randomly divided into two equally-sized groups: venlafaxine-treated and control. After mating, pregnant mice of venlafaxine-treated group were orally received the venlafaxine 35 mg/kg/day throughout pregnancy, while pregnant control mice did not receive any treatment. All pups were killed on postnatal day 21 and brain images were quantified using ImageJ software. The mRNA expression levels of SHANK3, TUBB5 and DDC of genes in pups' brain tissue samples were evaluated using quantitative real-time PCR method.
PRINCIPAL OBSERVATIONS
The mean brain size of pups was significantly smaller in the venlafaxine-treated group than in the control group. Results showed that the mRNA expression levels of SHANK3 and TUBB5 was significantly downregulated in venlafaxine-treated mice compared to control group. Expression of DDC gene didn't showed significant differences between two groups.
CONCLUSIONS
These results provide evidence that use of venlafaxine during pregnancy may affect the brain development in mice and altered the expression of SHANK3 and TUBB5 genes in brain tissue.
Topics: Animals; Female; Mice; Pregnancy; Aromatic-L-Amino-Acid Decarboxylases; Brain; Nerve Tissue Proteins; RNA, Messenger; Venlafaxine Hydrochloride
PubMed: 37601086
DOI: No ID Found -
Reproductive Toxicology (Elmsford, N.Y.) Sep 2023The chronic use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in human gynecomastia, mammoplasia,...
The chronic use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in human gynecomastia, mammoplasia, galactorrhea, and elevated breast cancer risk. As antidepressants are frequently used for postpartum depression (PPD) treatment, this study investigated the adverse effects of lactational exposure to venlafaxine (VENL, a selective SNRI) on mammary gland development and carcinogenesis in F1 female offspring. Thus, lactating Wistar rats (F0) received VENL by oral gavage at daily doses of 3.85, 7.7, or 15.4 mg/kg (N = 9, each group) from lactational day (LD 1) until the weaning of the offspring (LD 21). F1 female offspring were euthanized for mammary gland, and ovary histological analyses on the post-natal day (PND) 22 and 30 (1 pup/litter/period, N = 9, each group). At PND 22, other females (2 pups/litter, N = 18, each group) received a single dose of carcinogen N-methyl-N-nitrosourea (MNU, 50 mg/kg) intraperitoneally (i.p.) for tumor susceptibility assay until PND 250. Tumor incidence and latency were recorded and representative tumor samples were collected for histopathology. The results indicate that lactational exposure to VENL did not alter the development of the mammary gland (epithelial ductal tree or the mean number of terminal end buds), or the ovary (weight and primary, secondary, tertiary, and Graafian follicles) in prepubertal F1 female offspring. In addition, VENL exposure did not influence tumor incidence or tumor latency in adult female offspring that received MNU. Thus, the findings of this animal study indicated that lactational VENL exposure, a period similar to human PPD, did not exert an adverse effect on the mammary gland development at the prepubertal phase or on chemically induced mammary tumorigenesis in adult F1 female rats.
Topics: Pregnancy; Female; Humans; Rats; Animals; Lactation; Venlafaxine Hydrochloride; Rats, Wistar; Carcinogenesis; Prenatal Exposure Delayed Effects
PubMed: 37532207
DOI: 10.1016/j.reprotox.2023.108451 -
Journal of Hazardous Materials Oct 2023The dissipation kinetics and half-lives of selected organic micropollutants, including pharmaceuticals and others, were systematically investigated and compared among...
The dissipation kinetics and half-lives of selected organic micropollutants, including pharmaceuticals and others, were systematically investigated and compared among different soil types. While some pollutants (e.g., atorvastatin, valsartan, and bisphenol S) disappeared rapidly in all the tested soils, many of them (e.g., telmisartan, memantine, venlafaxine, and azithromycin) remained persistent. Irrespective of the soil characteristics, venlafaxine showed the lowest dissipation kinetics and the longest half-lives (250 to approximately 500 days) among the stable compounds. The highest first and second-order kinetics were, however, recorded for valsartan (k; 0.262 day) and atorvastatin (k; 33.8 g μg day) respectively. Nevertheless, more than 90% (i.e., DT) of all the rapidly dissipated compounds (i.e., atorvastatin, bisphenol S, and valsartan) disappeared from the tested soils within a short timescale (i.e., 5-36 days). Dissipation of pollutants that are more susceptible to microbial degradation (e.g., atorvastatin, bisphenol S, and valsartan) seems to be slower for soils possessing the lowest microbial biomass C (C) and total phospholipid fatty acids (PLFA), which also found statistically significant. Our results revealing the persistence of several organic pollutants in agricultural soils, which might impact the quality of these soils, the groundwater, and eventually on the related biota, is of high environmental significance.
Topics: Soil; Atorvastatin; Venlafaxine Hydrochloride; Soil Pollutants; Environmental Pollutants; Soil Microbiology
PubMed: 37531764
DOI: 10.1016/j.jhazmat.2023.132143 -
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 -
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 -
Journal of Affective Disorders Oct 2023Guidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced...
INTRODUCTION
Guidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, examining the association between comorbid AUD and depression outcomes.
METHODS
STAR*D was a real-world effectiveness trial starting with citalopram in level 1. Non-responding participants progressed through 3 other sequential treatment levels with different switch or augmentation options. Antidepressant outcomes were compared between MDD (n = 2826) and comorbid MDD and AUD (n = 864). Logistic regressions were performed to evaluate remission and response predictors in the total STAR*D sample and the AUD-comorbidity interaction.
RESULTS
Chi-squared tests showed no significant difference in response or remission rates from depression between groups across treatment levels. Higher Hamilton Rating Scale for Depression (HRSD) score was associated with overall lower odds of remission in treatment level 1 (OR = 0.93, p < 0.001) and 2 (OR = 0.95, p < 0.001), with no significant interaction with comorbid AUD. Higher baseline suicidality had overall lower odds of remission in level 1 (OR = 0.82, p < 0.001) and 2 (OR = 0.1, p < 0.001), but with comorbid AUD compared to no AUD, suicidality increased odds of level 1 remission (OR = 1.30, p = 0.012). In comorbid AUD in level 2, venlafaxine was associated with lower odds of remission (OR = 0.13, p = 0.013) and response (OR = 0.12, p = 0.006); bupropion with lower odds of response (OR = 0.22, p = 0.024).
LIMITATIONS
Open label study design and lack of alcohol use data.
CONCLUSIONS
Comorbid AUD may interact with predictors of antidepressant response in MDD and using venlafaxine or bupropion may be less effective. Addressing this comorbidity requires unique assessment and treatment approaches.
Topics: Humans; Depressive Disorder, Major; Venlafaxine Hydrochloride; Alcoholism; Bupropion; Antidepressive Agents; Treatment Outcome; Comorbidity
PubMed: 37467796
DOI: 10.1016/j.jad.2023.07.049 -
Epilepsy & Behavior : E&B Aug 2023Depression in persons with epilepsy (PWE) goes undiagnosed and untreated. Despite being common, there are no direct efficacy comparisons of available antidepressants in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Depression in persons with epilepsy (PWE) goes undiagnosed and untreated. Despite being common, there are no direct efficacy comparisons of available antidepressants in PWE. Our aim was to compare the effectiveness of Venlafaxine (VEN) and Escitalopram (ESCIT) in comorbid depression in PWE.
METHODS
In a single-center, prospective, double-blinded randomized controlled trial (RCT) 90 PWE (age ≥18 years) with mild to moderate depression, were randomized in a 1:1 ratio to receive ESCIT (5-20 mg/day) or VEN (37.5-150 mg/day) for 8 weeks. The primary outcome was to study differences in the efficacy, based on the change in scores of the Hamilton depression rating scale (HAM-D) at 8 weeks. Seizure frequency, QOLIE-31, adverse event profile, and medication adherence were secondary outcome measures.
RESULTS
Using the NDDI-E scale, we screened 350 PWE, 90 were enrolled. ITT analysis included all participants and the PP analysis included 40 participants to VEN group and 42 to ESCIT group. Baseline mean (±SD) HAM-D scores for both groups were similar (13.53 ± 3.27; 13.02 ± 3.57). The mean difference (95%CI) on HAM-D scores at 8 weeks was found to be significant within both groups (ITT/PP- VEN: 7.75(6.75, 8.79)/7.92 (7.06, 8.78); p < 0.001, ESCIT: 8.21 (7.39, 9.03)/8.23(7.43, 9.04); p < 0.001). However, there was no significant difference in the efficacy of VEN versus ESCIT at 8 weeks. A significant improvement in QOLIE-31 index and seizure frequency was observed from baseline in both the groups. 90% of those on VEN and 92.9% of those using ESCITadhered to the treatment at week 8. Adverse events were more in VEN group than the ESCIT group.
CONCLUSIONS
This study found that HAMD scores improved significantly in the ESCIT and VEN groups, despite the fact that there was no clinically meaningful difference observed between the two groups. Trials with a larger sample size and longer duration are required to establish whether ESCIT or VEN is superior.
Topics: Humans; Adolescent; Venlafaxine Hydrochloride; Escitalopram; Depression; Epilepsy; Seizures; Treatment Outcome; Double-Blind Method
PubMed: 37454503
DOI: 10.1016/j.yebeh.2023.109352 -
Neurochemistry International Oct 2023Antidepressants are used to treat depression and some anxiety disorders, including use in pregnant patients. The pharmacological actions of these drugs generally...
Antidepressants are used to treat depression and some anxiety disorders, including use in pregnant patients. The pharmacological actions of these drugs generally determine the uptake and metabolism of a series of neurotransmitters, such as serotonin, norepinephrine, or dopamine, along with an increase in BDNF expression. However, many aspects of antidepressant action remain unknown, particularly whether antidepressants interfere with normal neurodevelopment when taken by pregnant women. In order to reveal cellular and molecular implications crucial to the functioning of pathways related to antidepressant effects, we performed an investigation on neuronally differentiating human SH-SY5Y cells. To our knowledge, this is the first time human SH-SY5Y cells in cultures of purely neuronal cells induced by controlled differentiation with retinoic acid are followed by short-term 48-h exposure to 0.1-10 μM escitalopram or venlafaxine. Treatment with antidepressants (1 μM) did not affect the electrophysiological properties of SH-SY5Y cells. However, the percentage of mature neurons exhibiting voltage-gated sodium currents was substantially higher in cultures pre-treated with either antidepressant. After exposure to escitalopram or venlafaxine, we observed a concentration-dependent increase in activity-dependent BDNF promoter IV activation. The assessment of neurite metrics showed significant down-regulation of neurite outgrowth upon exposure to venlafaxine. Identified changes may represent links to molecular processes of importance to depression and be involved in neurodevelopmental alterations observed in postpartum children exposed to antidepressants antenatally.
Topics: Child; Female; Humans; Pregnancy; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Line, Tumor; Escitalopram; Neuroblastoma; Neuronal Outgrowth; Neurons; Venlafaxine Hydrochloride
PubMed: 37451345
DOI: 10.1016/j.neuint.2023.105571 -
International Journal of Molecular... Jul 2023About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely...
About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed.
Topics: Animals; Mice; Analgesics, Opioid; Mianserin; Venlafaxine Hydrochloride; Fluvoxamine; Mirtazapine; Fluoxetine; Reboxetine; Trazodone; Moclobemide; Depression; Antidepressive Agents; Naloxone; Dose-Response Relationship, Drug
PubMed: 37446323
DOI: 10.3390/ijms241311142 -
Neuropsychopharmacology : Official... Sep 2023Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans....
Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans. As consequence, energy metabolism imbalance has been commonly associated to several mental disorders, including depression. Here, by employing a metabolomic approach, we aimed to establish if differences in energy metabolite concentration may underlie the vulnerability and resilience in an animal model of mood disorder named chronic mild stress (CMS) paradigm. In addition, we have investigated the possibility that modulation of metabolite concentration may represent a pharmacological target for depression by testing whether repeated treatment with the antidepressant venlafaxine may normalize the pathological phenotype by acting at metabolic level. The analyses were conducted in the ventral hippocampus (vHip) for its key role in the modulation of anhedonia, a core symptom of patients affected by depression. Interestingly, we showed that a shift from glycolysis to beta oxidation seems to be responsible for the vulnerability to chronic stress and that vHip metabolism contributes to the ability of the antidepressant venlafaxine to normalize the pathological phenotype, as shown by the reversal of the changes observed in specific metabolites. These findings may provide novel perspectives on metabolic changes that could serve as diagnostic markers and preventive strategies for the early detection and treatment of depression as well as for the identification of potential drug targets.
Topics: Rats; Animals; Humans; Venlafaxine Hydrochloride; Rats, Wistar; Glucose; Antidepressive Agents; Anhedonia; Hippocampus; Stress, Psychological; Depression; Disease Models, Animal
PubMed: 37380799
DOI: 10.1038/s41386-023-01633-0