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Environmental Science & Technology Mar 2023The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore,...
The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore, the tissue-specific uptake and depuration kinetics of two pairs of pharmaceutical enantiomers, -(-)-metoprolol versus -(+)-metoprolol and -(+)-venlafaxine versus -(-)-venlafaxine, were studied in marine medaka () during a 28-day exposure and 14-day clearance period. The toxicokinetics of the studied pharmaceuticals, including uptake and depuration rate constants, depuration half-life (), and bioconcentration factor (BCF), were reported for the first time. The whole-fish results demonstrated a higher - than -venlafaxine bioaccumulation potential, whereas no significant difference was observed between - and -metoprolol. -desmethyl-metoprolol (ODM) and α-hydroxy-metoprolol (AHM) were the main metoprolol metabolites identified by suspect screening, and the ratios of ODM to AHM were 3.08 and 1.35 for - and -metoprolol, respectively. ,-Didesmethyl-venlafaxine (NODDV) and -desmethyl-venlafaxine (NDV) were the main venlafaxine metabolites, and the ratios of NODDV to NDV were 1.55 and 0.73 for - and -venlafaxine, respectively. The highest tissue-specific BCFs of the four enantiomers were all found in the eyes, meriting in-depth investigation.
Topics: Animals; Venlafaxine Hydrochloride; Oryzias; Metoprolol; Tissue Distribution; Pharmaceutical Preparations
PubMed: 36877486
DOI: 10.1021/acs.est.2c08379 -
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 -
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 -
British Journal of Clinical Pharmacology Apr 2017Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but their... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIMS
Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but their mechanisms of action in humans remain unclear. The present study aimed to explore how oxycodone (an opioid) and venlafaxine (an SNRI) modulate spinal and supraspinal sensory processing.
METHODS
Twenty volunteers were included in a randomized, double-blinded, three-way (placebo, oxycodone, venlafaxine), crossover study. Spinal and full scalp cortical evoked potentials (EPs) to median nerve stimulation were recorded before and after 5 days of treatment. Assessment of the central effects of the three treatments involved: (i) amplitudes and latencies of spinal EPs (spinal level); (ii) amplitudes and latencies of the P14 potential (subcortical level); (iii) amplitudes and latencies of early and late cortical EPs (cortical level); (iv) brain sources underlying early cortical Eps; and (v) brain networks underlying the late cortical EPs.
RESULTS
In the venlafaxine arm, the spinal P11 and the late cortical N60-80 latencies were reduced by 1.8% [95% confidence interval (CI) 1.7%, 1.9%) and 5.7% (95% CI 5.3%, 6.1%), whereas the early cortical P25 amplitude was decreased by 7.1% (95%CI 6.1%, 8.7%). Oxycodone increased the subcortical P14 [+25% (95% CI 22.2%, 28.6%)], early cortical N30 [+12.9% (95% CI 12.5%, 13.2%)] amplitudes and the late cortical N60-80 latency [+2.9% (95% CI 1.9%, 4.0%)]. The brainstem and primary somatosensory cortex source strengths were increased by 66.7% (95% CI 62.5%, 75.0%) and 28.8% (95% CI 27.5%, 29.6%) in the oxycodone arm, whereas the primary somatosensory cortex strength was decreased in the venlafaxine arm by 18.3% (95% CI 12.0%, 28.1%).
CONCLUSIONS
Opioids and SNRI drugs exert different central effects. The present study contributed to the much-needed human models of the mechanisms of action of drugs with effects on the central nervous system.
Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Second-Generation; Cross-Over Studies; Double-Blind Method; Electric Stimulation; Evoked Potentials, Somatosensory; Humans; Male; Median Nerve; Oxycodone; Venlafaxine Hydrochloride; Young Adult
PubMed: 27808426
DOI: 10.1111/bcp.13177 -
Venlafaxine deposition in the zygote disrupts the endocrine control of growth in juvenile zebrafish.Environmental Research Nov 2021The antidepressant venlafaxine can be found at levels nearing μg/L in waterways receiving municipal wastewater effluent, exposing non-target organisms, such as fish, to...
The antidepressant venlafaxine can be found at levels nearing μg/L in waterways receiving municipal wastewater effluent, exposing non-target organisms, such as fish, to this chemical. We showed previously that zygotic exposure to venlafaxine alters neurodevelopment and behaviour in zebrafish (Danio rerio) larvae. Here, we tested the hypothesis that the zygotic deposition of venlafaxine disrupts endocrine pathways related to growth in zebrafish. This was carried out by microinjecting embryos (1-4 cell stage) with either 0, 1, or 10 ng venlafaxine. Zygotic venlafaxine deposition reduced the growth of fish after 30 days post-fertilization. Specific growth rate was particularly impacted by 1 ng venlafaxine. This growth retardation corresponded with the disruption of endocrine pathways involved in growth and metabolism. Venlafaxine exposed embryos displayed reduced transcript abundance of key genes involved in anabolic hormone action. Early-life venlafaxine exposure also reduced whole-body insulin and glucose content in juveniles. Target-tissue glucose uptake measurements indicated that high venlafaxine deposition preferentially increased glucose uptake to the brain. Zygotic venlafaxine did not affect feed intake nor altered the transcript abundance of key feeding-related peptides. Taken together, zygotic venlafaxine deposition compromises zebrafish growth by disrupting multiple endocrine pathways, and this study has identified key markers for potential use in risk assessment.
Topics: Animals; Larva; Venlafaxine Hydrochloride; Water Pollutants, Chemical; Zebrafish; Zygote
PubMed: 34252433
DOI: 10.1016/j.envres.2021.111665 -
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 -
Acta Psychiatrica Scandinavica Jun 2018Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response.
METHOD
We conducted a comprehensive systematic review and meta-analysis of placebo-controlled, double-blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder.
RESULTS
We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre-postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (-2.51 vs. -2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor.
CONCLUSION
Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included.
Topics: Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Placebo Effect; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 29603140
DOI: 10.1111/acps.12881 -
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