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Medicina (Kaunas, Lithuania) Apr 2022Venlafaxine (VEN) is considered to be one of the most effective antidepressants. It belongs to the group of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors... (Review)
Review
Venlafaxine (VEN) is considered to be one of the most effective antidepressants. It belongs to the group of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs). NA and 5-HT have receptors on the surface of platelets and are involved in platelet aggregation. In this case study, we present the case of a patient treated for one of the types of myeloproliferative neoplasm (MPN), essential thrombocythemia (ET), in whom VEN was added to pharmacotherapy during the treatment of a severe episode of depression with psychotic symptoms. We observed a gradual reduction in platelet count when increasing the dose of VEN. We also present a narrative review of literature about the effect of VEN on platelet counts and activity. We conclude that, in the group of patients taking VEN, attention should be paid to the rare adverse effect of a decrease in the number of platelets.
Topics: Cyclohexanols; Humans; Platelet Count; Serotonin; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 35630043
DOI: 10.3390/medicina58050626 -
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 -
Drug Metabolism and Disposition: the... Oct 2020Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common Chinese herbal medicine consisting of and , have a high likelihood of combination usage...
Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common Chinese herbal medicine consisting of and , have a high likelihood of combination usage in patients with depression with gastrointestinal complications. ZJP exhibits inhibitory effects on recombinant human cytochrome P450 isoenzymes (rhP450s), especially on CYP2D6, whereas VEN undergoes extensive metabolism by CYP2D6. From this perspective, we investigated the influence of ZJP on the metabolism of VEN in vitro and in rats for the first time. In this study, ZJP significantly inhibited the metabolism of VEN in both rat liver microsomes (RLM) and human liver microsomes (HLM); meanwhile, it inhibited the -demethylation catalytic activity of RLM, HLM, rhCYP2D6*1/*1, and rhCYP2D6*10/*10, primarily through CYP2D6, with IC values of 129.9, 30.5, 15.4, and 2.3 μg/ml, respectively. Furthermore, the inhibitory effects of ZJP on hepatic metabolism and pharmacokinetics of VEN could also be observed in the pharmacokinetic study of rats. The area under drug concentration-time curve- of VEN and its major metabolite -desmethylvenlafaxine (ODV) increased by 39.6% and 22.8%, respectively. The hepatic exposure of ODV decreased by 57.2% 2 hours after administration ( = 0.014). In conclusion, ZJP displayed inhibitory effects on hepatic metabolism and pharmacokinetics of VEN in vitro and in rats mainly through inhibition of CYP2D6 activity. The human pharmacokinetic interaction between ZJP and VEN and its associated clinical significance needed to be seriously considered. SIGNIFICANCE STATEMENT: Zuojin Pill, a commonly used Chinese herbal medicine, demonstrates significant inhibitory effects on hepatic metabolism and pharmacokinetics of venlafaxine in vitro and in rats mainly through suppression of CYP2D6 activity. The human pharmacokinetic interaction between Zuojin Pill and venlafaxine and its associated clinical significance needs to be seriously considered.
Topics: Administration, Oral; Animals; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Inhibitory Concentration 50; Male; Rats; Recombinant Proteins; Venlafaxine Hydrochloride
PubMed: 32561594
DOI: 10.1124/dmd.120.000048 -
Inflammopharmacology Oct 2021Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory...
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used to treat depression. Previous studies demonstrated its anti-nociceptive and anti-inflammatory activities through the suppression of pro-inflammatory cytokines. Present research aimed to explore its anti-arthritic potential. Different in-vitro assays including egg albumin, bovine serum albumin denaturation and human red blood cell (RBC) membrane stabilization assays along with in-vivo models of formaldehyde and complete Freund's adjuvant-induced arthritis were used to study its anti-arthritic effect. Venlafaxine inhibited egg albumin and bovine serum albumin denaturation and preserve the integrity of red blood cells membrane in concentration-dependent manner. In formaldehyde-induced arthritis venlafaxine significantly (p < 0.001) reduced the paw edema on treatment for 10 days. Chronic administration of venlafaxine for 28 days in Freund's adjuvant-induced arthritis model decreased the paw volume (p < 0.001), arthritic index (p < 0.01), flexion pain score (p < 0.05), mobility score (p < 0.05), and improved the stance score (p < 0.05). Venlafaxine also significantly declined the rheumatoid factor (p < 0.01) and C-reactive protein (p < 0.05) levels and increased the RBC count (p < 0.01) and Hb value (p < 0.001). Upon PCR analysis venlafaxine remarkably turndown the mRNA expression of TNF-α, IL-6, IL-1β, and COX-2. Taken together it is inferred from current findings that venlafaxine possesses the significant anti-arthritic activity and could be a potential therapeutic option for the treatment of rheumatoid arthritis.
Topics: Animals; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cyclooxygenase 2; Dose-Response Relationship, Drug; Down-Regulation; Erythrocytes; Female; Freund's Adjuvant; Humans; Interleukin-1beta; Interleukin-6; Male; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Venlafaxine Hydrochloride
PubMed: 34302591
DOI: 10.1007/s10787-021-00849-0 -
Sensors (Basel, Switzerland) Jun 2020Venlafaxine (VEN), as one of the popular anti-depressants, is widely utilized for the treatment of major depressive disorder, panic disorder, as well as anxiety. This... (Review)
Review
Venlafaxine (VEN), as one of the popular anti-depressants, is widely utilized for the treatment of major depressive disorder, panic disorder, as well as anxiety. This drug influences the chemicals in the brain, which may result in imbalance in depressed individuals. However, venlafaxine and its metabolites are contaminants in water. They have exerted an adverse influence on living organisms through their migration and transformation in various forms of adsorption, photolysis, hydrolysis, and biodegradation followed by the formation of various active compounds in the environment. Hence, it is crucial to determine VEN with low concentrations in high sensitivity, specificity, and reproducibility. Some analytical techniques have been practically designed to quantify VEN. However, electroanalytical procedures have been of interest due to the superior advantages in comparison to conventional techniques, because such methods feature rapidity, simplicity, sensitivity, and affordability. Therefore, this mini-review aims to present the electrochemical determination of VEN with diverse electrodes, such as carbon paste electrodes, glassy carbon electrodes, mercury-based electrodes, screen-printed electrodes, pencil graphite electrodes, and ion-selective electrodes.
Topics: Antidepressive Agents; Carbon; Electrochemical Techniques; Electrodes; Graphite; Reproducibility of Results; Venlafaxine Hydrochloride; Water Pollutants, Chemical
PubMed: 32630056
DOI: 10.3390/s20133675 -
Environmental Science & Technology Nov 2020The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is present in surface waters downstream of wastewater treatment plants. We...
The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is present in surface waters downstream of wastewater treatment plants. We previously showed that zygotic venlafaxine deposition alters larval behavior in zebrafish (), but the mechanisms were unknown. Here we tested the hypothesis that venlafaxine disrupts central serotonergic development, leading to impaired behavioral responses in zebrafish larvae. This was tested by microinjecting embryos with venlafaxine immediately after fertilization and performing spatial distribution of serotonin immunoreactivity, as well as characterizing target genes involved in serotonin turnover in the zebrafish brain. We provide evidence that venlafaxine exposure reduces serotonin immunoreactivity and tyrosine hydroxylase-positive cell populations in specific larval brain regions, and this corresponded with reduced larval activity observed in the drug-exposed group. Lowered serotonin was not due to either reduced synthesis or increased breakdown capacity. However, co-injection of serotonin alongside venlafaxine in embryos recovered brain serotonin immunoreactivity, tyrosine hydroxylase-positive cell populations, and rescued venlafaxine-mediated behavioral changes. Overall, our results demonstrate for the first time that early life exposure to venlafaxine perturbs brain development, which may be due to reduced serotonin, leading to altered larval behavior in zebrafish.
Topics: Animals; Brain; Serotonin; Venlafaxine Hydrochloride; Water Pollutants, Chemical; Zebrafish
PubMed: 33142061
DOI: 10.1021/acs.est.0c06032 -
Clinical Pharmacology in Drug... Jan 2022This single-center, randomized, 3-way crossover thorough QT study evaluated the effect of steady-state supratherapeutic venlafaxine (Effexor) on cardiac repolarization.... (Randomized Controlled Trial)
Randomized Controlled Trial
This single-center, randomized, 3-way crossover thorough QT study evaluated the effect of steady-state supratherapeutic venlafaxine (Effexor) on cardiac repolarization. Fifty-four healthy adults received double-blinded extended-release venlafaxine 450 mg/d and placebo and open-label positive-control moxifloxacin 400 mg. The postdose QT intervals corrected for heart rate using the Fridericia formula (QTcF) were assessed on day 14 with an analysis of covariance using a mixed-effects model. At each time, the upper bound of the 2-sided 90%CI for time-matched least-squares (LS) mean difference between venlafaxine and placebo did not exceed the predefined cutoff of 10 milliseconds; the highest 90%CI upper bound was 5.8 milliseconds 24 hours postdose, demonstrating the lack of effect of venlafaxine on the QTc interval (primary objective). Assay sensitivity was established because the lower bound of the 2-sided 90%CI for LS mean difference in QTcF between moxifloxacin and placebo was 7.413 milliseconds on day 14 (postdose 3 hours). The exposure-response analysis demonstrated no evidence of increase in QTcF with increase in venlafaxine and desvenlafaxine concentrations. Also, supratherapeutic venlafaxine was found to be safe and well tolerated. Overall, the results demonstrated the lack of significant prolongation of the QTc interval with supratherapeutic venlafaxine 450 mg/d.
Topics: Adult; Double-Blind Method; Electrocardiography; Fluoroquinolones; Healthy Volunteers; Humans; Long QT Syndrome; Venlafaxine Hydrochloride
PubMed: 34242472
DOI: 10.1002/cpdd.989 -
Placenta Jan 2022Depression is frequent among pregnant women and decision for treatment with antidepressants needs careful consideration of risks for the fetus. Since data regarding...
INTRODUCTION
Depression is frequent among pregnant women and decision for treatment with antidepressants needs careful consideration of risks for the fetus. Since data regarding fetal antidepressant exposure are rare, we aimed to evaluate transplacental transfer of venlafaxine, a selective norepinephrine reuptake inhibitor.
METHODS
Ex vivo human placental perfusion experiments were conducted in double closed set-up. Venlafaxine (18.1 ± 2.1 μg/L) was offered in maternal circuit and maternal-to-fetal transfer was monitored over a period of 3h. Venlafaxin and O-desmethylvenlafaxine concentrations were determined by HPLC-MS in maternal and fetal perfusion medium.
RESULTS
We observed maternal-to-fetal transfer of venlafaxine within 5 min perfusion. The concentration equilibrium was approximated between maternal (7.5 ± 0.5 μg/L) and fetal (6.5 ± 0.6 μg/L) compartment at time point 180 min, which corresponds to a fetal-maternal (FM) ratio of 0.89.
DISCUSSION
Our results are comparable with in vivo data from an observational study which emphasizes that the ex vivo placental perfusion model is suitable for systematic evaluation of fetal antidepressant exposure.
Topics: Female; Humans; In Vitro Techniques; Perfusion; Placenta; Pregnancy; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 34894602
DOI: 10.1016/j.placenta.2021.12.007 -
The Journal of Neuroscience : the... May 2020Emerging evidence suggests that there is a reduction in overall cortical excitatory to inhibitory balance in major depressive disorder (MDD), which afflicts ∼14%-20%...
Emerging evidence suggests that there is a reduction in overall cortical excitatory to inhibitory balance in major depressive disorder (MDD), which afflicts ∼14%-20% of individuals. Reduced pyramidal cell arborization occurs with stress and MDD, and may diminish excitatory neurotransmission. Enhanced deposition of perineuronal net (PNN) components also occurs with stress. Since parvalbumin-expressing interneurons are the predominant cell population that is enveloped by PNNs, which enhance their ability to release GABA, excess PNN deposition likely increases pyramidal cell inhibition. In the present study, we investigate the potential for matrix metalloprotease-9 (MMP-9), an endopeptidase secreted in response to neuronal activity, to contribute to the antidepressant efficacy of the serotonin/norepinephrine reuptake inhibitor venlafaxine in male mice. Chronic venlafaxine increases MMP-9 levels in murine cortex, and increases both pyramidal cell arborization and PSD-95 expression in the cortex of WT but not MMP-9-null mice. We have previously shown that venlafaxine reduces PNN deposition and increases the power of γ oscillations in conventionally housed mice. γ power is increased with pyramidal cell disinhibition and with remission from MDD. Herein we observe that PNN expression is increased in a corticosterone-induced stress model of disease and reduced by venlafaxine. Compared with mice that receive concurrent venlafaxine, corticosterone-treated mice also display reduced γ power and impaired working memory. Autopsy-derived PFC samples show elevated MMP-9 levels in antidepressant-treated MDD patients compared with controls. These preclinical and postmortem findings highlight a link between extracellular matrix regulation and MDD. Reduced excitatory neurotransmission occurs with major depressive disorder, and may be normalized by antidepressant treatment. Underlying molecular mechanisms are, however, not well understood. Herein we investigate a potential role for an extracellular protease, released from neurons and known to play a role in learning and memory, in antidepressant-associated increases in excitatory transmission. Our data suggest that this protease, matrix metalloprotease-9, increases branching of excitatory neurons and concomitantly attenuates the perineuronal net to potentially reduce inhibitory input to these neurons. Matrix metalloprotease-9 may thus enhance overall excitatory/inhibitory balance and neuronal population dynamics, which are important to mood and memory.
Topics: Adult; Aged; Animals; Cells, Cultured; Cerebral Cortex; Depressive Disorder, Major; Female; Gamma Rhythm; Humans; Male; Matrix Metalloproteinase 9; Memory, Short-Term; Mice; Mice, Inbred C57BL; Middle Aged; Neural Inhibition; Pyramidal Cells; Serotonin and Noradrenaline Reuptake Inhibitors; Stress, Psychological; Venlafaxine Hydrochloride
PubMed: 32269106
DOI: 10.1523/JNEUROSCI.2387-19.2020 -
Journal of Opioid Management 2019A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes...
A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes developed his first manic episode following use of tramadol. Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs. In addition, mania is not listed as a potential clinical side effect-further illustrating this relative rarity. Due to tramadol's SNRI activity, there is definitive risk for mood lability in individuals managed with tramadol and other serotonergic medications as seen in this patient. The authors findings suggest the need for greater risk consideration when prescribing tramadol with other related agents such as venlafaxine.
Topics: Analgesics, Opioid; Bipolar Disorder; Depressive Disorder, Major; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Tramadol; Venlafaxine Hydrochloride
PubMed: 31637686
DOI: 10.5055/jom.2019.0519