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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 -
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 -
Neurology India 2022
Topics: Anti-Inflammatory Agents, Non-Steroidal; Headache; Humans; Indomethacin; Venlafaxine Hydrochloride
PubMed: 36076682
DOI: 10.4103/0028-3886.355083 -
Annals of Palliative Medicine Jul 2021Generalized anxiety disorder (GAD) is partly attibuted to the dysregulation of nuero-inflammation which can be mediated by adiponectin. We conducted this study was to...
BACKGROUND
Generalized anxiety disorder (GAD) is partly attibuted to the dysregulation of nuero-inflammation which can be mediated by adiponectin. We conducted this study was to explore the characteristics of peripheral adiponectin and its role in predicting treatment outcome in patients with generalized anxiety disorder (GAD) treated by escitalopram or venlafaxine.
METHODS
A total of 70 untreated GAD inpatients who met the diagnosis criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) were enrolled and randomly selected for treatment with escitalopram (n=36) or venlafaxine (n=34) for 8 weeks. The serum adiponectin level of GAD and healthy controls (HCs) was measured by enzyme-linked immunosorbent assay (ELISA) before treatment. Hamilton Anxiety Rating Scale (HAM-A) assessment was conducted at baseline and at 1, 2, 4, and 8 weeks after treatment respectively. Serum adiponectin levels were compared between GAD patients and HCs, as well as between remission and nonremission cases; the correlation between baseline adiponectin level and HAM-A reduction rate were also analyzed.
RESULTS
The serum adiponectin levels were higher in GAD patients compared to HCs (t=2.304; P=0.023), the serum adiponectin levels were higher in remission cases compared to nonremission cases (t=2.255, P=0.027), and the receiver operating characteristic (ROC) area in predicting treatment remission was 0.652±0.066 (P=0.029). The correlation between baseline adiponectin level and HAM-A reduction rate of GAD cases treated with escitalopram and venlafaxine in the endpoint was 0.362 (P=0.030) and -0.026 (P=0.883), respectively, and the ROC area of baseline adiponectin level in predicting treatment remission was 0.72±0.086 (P=0.024) and 0.473±0.102 (P=0.469), respectively.
CONCLUSIONS
Peripheral adiponectin is upregulated in GAD, and it seems higher baseline adiponectin level predicts a better treatment remission treated by escitalopram but not with venlafaxine, which suggests adiponectin maybe a potential key biomarker in Chinese GAD.
Topics: Adiponectin; Anxiety Disorders; Citalopram; Humans; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 34353051
DOI: 10.21037/apm-21-1542 -
Molecular Psychiatry Jul 2020Although major depressive disorder (MDD) is associated with altered functional coupling between disparate neural networks, the degree to which such measures are... (Randomized Controlled Trial)
Randomized Controlled Trial
Although major depressive disorder (MDD) is associated with altered functional coupling between disparate neural networks, the degree to which such measures are ameliorated by antidepressant treatment is unclear. It is also unclear whether functional connectivity can be used as a predictive biomarker of treatment response. Here, we used whole-brain functional connectivity analysis to identify neural signatures of remission following antidepressant treatment, and to identify connectomic predictors of treatment response. 163 MDD and 62 healthy individuals underwent functional MRI during pre-treatment baseline and 8-week follow-up sessions. Patients were randomized to escitalopram, sertraline or venlafaxine-XR antidepressants and assessed at follow-up for remission. Baseline measures of intrinsic functional connectivity between each pair of 333 regions were analyzed to identify pre-treatment connectomic features that distinguish remitters from non-remitters. We then interrogated these connectomic differences to determine if they changed post-treatment, distinguished patients from controls, and were modulated by medication type. Irrespective of medication type, remitters were distinguished from non-remitters by greater connectivity within the default mode network (DMN); specifically, between the DMN, fronto-parietal and somatomotor networks, the DMN and visual, limbic, auditory and ventral attention networks, and between the fronto-parietal and somatomotor networks with cingulo-opercular and dorsal attention networks. This baseline hypo-connectivity for non-remitters also distinguished them from controls and increased following treatment. In contrast, connectivity for remitters was higher than controls at baseline and also following remission, suggesting a trait-like connectomic characteristic. Increased functional connectivity within and between large-scale intrinsic brain networks may characterize acute recovery with antidepressants in depression.
Topics: Adult; Antidepressive Agents; Biomarkers; Brain; Citalopram; Connectome; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Remission Induction; Sertraline; Venlafaxine Hydrochloride; Young Adult
PubMed: 31695168
DOI: 10.1038/s41380-019-0574-2 -
International Journal of Molecular... Nov 2021The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by...
The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants' and neuroleptic drugs' toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.
Topics: Amitriptyline; Animals; Antidepressive Agents; Antipsychotic Agents; Cell Line; Escitalopram; Fluoxetine; G2 Phase Cell Cycle Checkpoints; Gene Expression Regulation; Imipramine; Male; Mice; Micronuclei, Chromosome-Defective; Mirtazapine; Models, Biological; Olanzapine; Organ Specificity; Reboxetine; Reproduction; Signal Transduction; Spermatogenesis; Telomeric Repeat Binding Protein 1; Telomeric Repeat Binding Protein 2; Time Factors; Venlafaxine Hydrochloride
PubMed: 34769286
DOI: 10.3390/ijms222111855 -
Translational Psychiatry Aug 2019The identification of biomarkers of response might speed drug development and set the premises to assist clinical practice in psychiatry. In this work, we evaluated a... (Comparative Study)
Comparative Study Randomized Controlled Trial
The identification of biomarkers of response might speed drug development and set the premises to assist clinical practice in psychiatry. In this work, we evaluated a panel of peripheral biomarkers (including IL-6, IL-10, TNF-α, TNFRII, BDNF, CRP, MMP9 and PAI1) in depressed patients receiving paroxetine, venlafaxine, or placebo. Samples were obtained from two randomised placebo-controlled studies evaluating the efficacy and tolerability of a novel drug candidate, using either paroxetine or venlafaxine as active comparators. In both studies, the biomarker candidates were analysed in plasma collected at randomization and after 10 weeks of treatment with either placebo or active comparator (for a total of 106 and 108 subjects in the paroxetine and venlafaxine study, respectively). Data were obtained by multiplexing sandwich-ELISA system. Data were subjected to statistical analysis to assess their correlation with baseline severity and with response outcome. Increases in biomarker levels were correlated with reduction in depression severity for TNF-α, IL-6 IL-10 and CRP. Response to paroxetine treatment correlated with baseline IL-10, IL-6 and TNF-α levels, with the strongest signal being observed in males. In the venlafaxine study, a correlation was observed only between CRP level at randomisation and response, suggesting differences between the two active treatments and the two studies. Our investigations suggest that a combination of pro- and anti-inflammatory cytokines may predict response outcome in patients treated with paroxetine. The potential for IL-10, IL-6 and TNF-α as response biomarkers for a wider range of antidepressants warrants further investigations in clinical trials with other monoamine reuptake inhibitors.
Topics: Adult; Biomarkers; C-Reactive Protein; Depressive Disorder, Major; Female; Humans; Interleukin-10; Interleukin-6; Male; Middle Aged; Paroxetine; Treatment Outcome; Tumor Necrosis Factor-alpha; Venlafaxine Hydrochloride; Young Adult
PubMed: 31375659
DOI: 10.1038/s41398-019-0521-7 -
Drug Design, Development and Therapy 2019To investigate the effects of Chinese herb Danzhi Xiaoyao pills on the pharmacokinetics of venlafaxine and its metabolites O-desmethylvenlafaxine (ODV) and...
OBJECTIVE
To investigate the effects of Chinese herb Danzhi Xiaoyao pills on the pharmacokinetics of venlafaxine and its metabolites O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) in beagles by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
METHODS
Six beagles (half male, half female) were chosen to test, being fasted before the experiment but having free access to drinking water 1 day before being fed drugs. After oral administration of venlafaxine hydrochloride tablets (10.28 mg/kg), the blood samples were collected in succession at different points in time. After 1-week washout period, Danzhi Xiaoyao pills (0.6g/kg) were given through oral administration to the six beagles every morning until the 7th day, venlafaxine hydrochloride tablets (10.28 mg/kg) were given after feeding Danzhi Xiaoyao pills (0.6g/kg) half an hour and blood samples were collected continuously at different points. All samples were analyzed by UPLC-MS/MS, and the main pharmacokinetic parameters of venlafaxine, ODV and NDV were computed by DAS 2.0.
RESULTS
The C of the venlafaxine group (control group) and the combination group (experimental group) were (2267.26±252.89) ng/mL and (1542.64±190.73) ng/mL, respectively. The AUC of the two groups were (13,934.79±3609.23) ng·h/mL and (8001.91±2167.58) ng·h/mL, respectively. The ODV C of the two groups were (2253.80±215.81) ng/mL and (2721.37±118.20) ng/mL, and AUC were (13,974.99±2784.04) ng·h/mL and (17,539.44±1894.29) ng·h/mL, respectively. The NDV C of the two groups were (50.98±5.76) ng/mL and (58.74±12.33) ng/mL, and AUC were (179.26±34.94) ng·h/mL and (220.68±51.41) ng·h/mL, respectively. After administration of Danzhi Xiaoyao pills, the C and AUC of venlafaxine decreased significantly, indicating that the plasma exposure of venlafaxine decreased. The increase of C and AUC of ODV and NDV indicated a rise in plasma exposure.
CONCLUSION
Danzhi Xiaoyao pills can accelerate the metabolism of venlafaxine in beagles. In clinical, when venlafaxine was co-administrated with Danzhi Xiaoyao pills, dose adjustment of venlafaxine should be taken into account.
Topics: Animals; Area Under Curve; Chromatography, Liquid; Cyclohexanols; Desvenlafaxine Succinate; Dogs; Drugs, Chinese Herbal; Female; Male; Tablets; Tandem Mass Spectrometry; Venlafaxine Hydrochloride
PubMed: 31571835
DOI: 10.2147/DDDT.S221927 -
Clinical Psychopharmacology and... Aug 2021A 76-year-old male presented with a recurrent depressive episode, an unsteady gait and cognitive impairment. Extensive blood tests, including hemogram, biochemical...
A 76-year-old male presented with a recurrent depressive episode, an unsteady gait and cognitive impairment. Extensive blood tests, including hemogram, biochemical tests, folic acid, vitamin B12, and thyroid hormone, showed normal results. With the exception of the unsteady gait, neurological examination was negative. Brian magnetic resonance imaging (MRI) showed the typical feature of central pontine myelinolysis (CPM); however, there was no history of alcoholism, liver transplantation, malnutrition or rapid correction of hyponatremia. The patient had taken venlafaxine to treat major depressive disorder for more than 20 years. After discontinuation of venlafaxine, the unsteady gait gradually resolved, and subsequent MRI revealed reduction of the lesions over 6 months. We discuss herein the possible correlation between chronic use of venlafaxine and CPM.
PubMed: 34294627
DOI: 10.9758/cpn.2021.19.3.564 -
Scientific Reports Dec 2022A novel sustainable, simple, sensitive, and green spectrofluorimetric method was developed for the concurrent estimation of venlafaxine and agomelatine in...
A novel sustainable, simple, sensitive, and green spectrofluorimetric method was developed for the concurrent estimation of venlafaxine and agomelatine in pharmaceuticals and biological fluids. The method relies on synchronous fluorescence spectroscopy, where venlafaxine and agomelatine were measured at 276 and 328 nm, respectively, using Δλ of 20 nm. The potential factors affecting the fluorescence intensity were optimized by the one-factor-at-a-time (OFAT) strategy, where synchronous fluorescence intensity was significantly enhanced using a 1% w/v sodium dodecyl sulfate micellar system. The method was fully validated and exhibited excellent linearity (r > 0.999 for both drugs) with very low limits of detection (LODs) in the range of 0.14-0.84 ng/mL. Consequently, the proposed approach was efficiently adopted to analyze the co-administered drugs in their pharmaceuticals and in spiked human plasma with excellent % recovery between 97.4 and 102.2%. Finally, the method's greenness was evaluated using different metric tools, including Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE), which proved its excellent greenness.
Topics: Humans; Venlafaxine Hydrochloride; Spectrometry, Fluorescence; Acetamides; Pharmaceutical Preparations
PubMed: 36581643
DOI: 10.1038/s41598-022-26827-2