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European Neuropsychopharmacology : the... Feb 2024Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is...
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is therefore desirable to assign a given patient to the most promising individual treatment option as early as possible. We used a polygenic score (PGS) informed electroencephalography (EEG) data-driven approach to identify potential predictors for MDD treatment outcome. Post-hoc we conducted exploratory analyses in order to understand the results in depth. First, an EEG independent component analysis produced 54 functional brain networks in a large heterogeneous cohort of psychiatric patients (n = 4,045; 5-84 yrs.). Next, the network that was associated to PGS for antidepressant-response (PRS-AR) in an independent sample (n = 722) was selected: an age-related posterior alpha network that explained >60 % of EEG variance, and was highly stable over recording time. Translational analyses were performed in two other independent datasets to examine if the network was predictive of psychopharmacotherapy (n = 535) and/or repetitive transcranial magnetic stimulation (rTMS) and concomitant psychotherapy (PT; n = 186) outcome. The network predicted remission to venlafaxine (p = 0.015), resulting in a normalized positive predicted value (nPPV) of 138 %, and rTMS + PT - but in opposite direction for women (p = 0.002) relative to men (p = 0.018) - yielding a nPPV of 131 %. Blinded out-of-sample validations for venlafaxine (n = 29) and rTMS + PT (n = 36) confirmed the findings for venlafaxine, while results for rTMS + PT could not be replicated. These data suggest the existence of a relatively stable EEG posterior alpha aging network related to PGS-AR that has potential as MDD treatment predictor.
Topics: Male; Humans; Female; Venlafaxine Hydrochloride; Transcranial Magnetic Stimulation; Depressive Disorder, Major; Prefrontal Cortex; Antidepressive Agents; Treatment Outcome; Aging
PubMed: 38000196
DOI: 10.1016/j.euroneuro.2023.11.002 -
Georgian Medical News Sep 2023Two steps are able to lead to a significant decrease in the incidence of skin cancer overall and/or to its parallel and successful surgical treatment. The first step...
MORPHEAFORM BCC OF ALA NASI: A SUCCESSFUL DERMATOSURGICAL APPROACH BY TRANSPOSITION FLAP FROM THE ADJACENT AREA. CONTAMINATION OF VENLAFAXINE, BISOPROLOL AND OLANZAPINE WITH NITROSAMINES/NDSRIS: THE MOST LIKELY CAUSE OF SKIN CANCER DEVELOPMENT AND PROGRESSION.
Two steps are able to lead to a significant decrease in the incidence of skin cancer overall and/or to its parallel and successful surgical treatment. The first step concerns its non-occurrence or less frequent clinical manifestation and is largely related to the modern concept known as prevention, but not the one mainly related to solar radiation, but: 1) informing patients about the possible contamination of certain drugs with carcinogens/nitrosamines/NDSRIs and 2) making clinicians aware of the modern concept of limited to completely eliminated intake of nitrosamines/NDSRIs in medications. The ineffectiveness of either of these entities could in all likelihood be seen as one of the major causes of the headline growth in the incidence of skin cancer and keratinocytic cancer in particular. It is also because of this fact that the sun protection so recommended and advertised has been shown to be ineffective, yet it remains universally advertised. Polycontamination with Nitrosamines/NDSRIs within multimedication in polymorbid patients is the most serious obstacle (at the moment) for the current concept of skin cancer prevention to become a reality. The announced official "hypothetical contamination" of more than 250 drugs worldwide by the FDA in April 2023, and the establishment of permissive concentrations for 5 classes of carcinogenic activity of the nitrosamines/NDSRIs - effectively make any preventive step more than impossible or meaningless. The open question remains, how were the 5 subgroups for hypothetical carcinogenic potency of the carcinogens contained in the drugs created? On the basis of what data? What tumors occurred when these concentrations were exceeded? Data that remains hidden from the public and end users, but also data that guarantees the development of real (not hypothetical) skin tumours. The new FDA regulations also do not comment on the issues concerning the use of "hypothetical carcinogens" in the context of polycontamination and polymedication in polymorbid patients. Because of this fact, the follow-up of actual carcinomas after the intake of multiple "hypothetical carcinogens" would also seem to be not unimportant. And it turns out to be quite real and sobering to say the least. The second step, which concerns the successful treatment of skin cancer, is its early surgical treatment. This is the most promising approach, regardless of whether patients are exposed to permanent intake of carcinogens/nitrosamines/NDSRIs in the drugs. We report an 86-year-old patient, who, as part of his polymedication and polymorbidity, takes 3 drugs that, according to the official FDA list of 2023, have strictly defined reference limits for potentially available "hypothetical carcinogens": bisoprolol/carcinogenic potency class 4, olanzapine/ carcinogenic potency class 5 and venlafaxine/ carcinogenic potency class 1. The described patient developed "real carcinoma" after combined long-term intake of the "hypothetical carcinogens" announced in the official FDA lists from April 2023. Proceeding from common sense, regulators in the face of the FDA should have already long observed the development of a heterogeneous type of tumors to be able to determine 1) the potency of the 5 subclasses of carcinogens in the drugs and 2) their reference values. Moreover- they should also have the exact information why which carcinogen in which drug causes which type of tumor. Otherwise, the FDA should not announce its detailed recommendations to drug manufacturers. The present patient was successfully treated surgically by a transposition adjacent flap. The optimal dermatosurgical and reconstructive methodologies for the treatment of tumors in the ala nasi area are discussed.
Topics: Humans; Aged, 80 and over; Nitrosamines; Bisoprolol; Olanzapine; Venlafaxine Hydrochloride; Skin Neoplasms; Carcinogens
PubMed: 37991952
DOI: No ID Found -
Neuropharmacology Feb 2024The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake...
The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar hypersensitivity induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects.
Topics: Humans; Female; Rats; Animals; Venlafaxine Hydrochloride; Vulvodynia; Anti-Anxiety Agents; Serotonin; Neuroinflammatory Diseases; Selective Serotonin Reuptake Inhibitors; Norepinephrine; Chronic Pain; gamma-Aminobutyric Acid; Analgesics
PubMed: 37984764
DOI: 10.1016/j.neuropharm.2023.109788 -
International Journal of Clinical... Feb 2024A 70-year-old male taking venlafaxine for depression developed interstitial pneumonia and was admitted with shortness of breath and dyspnea. A computed tomography (CT)...
A 70-year-old male taking venlafaxine for depression developed interstitial pneumonia and was admitted with shortness of breath and dyspnea. A computed tomography (CT) chest scan showed diffuse multiple lung lesions in both lungs, suggesting interstitial changes with inflammation or exudation. Compared with the CT chest scan 1 month earlier, there were significant progresses and new findings. The clinical diagnosis was interstitial pneumonia with pulmonary infection. The patient had been treated with fluvoxamine 100 mg/day, duloxetine 60 mg/day, venlafaxine 75 mg/day for depression over the past 4 months. The exacerbation of interstitial pneumonia was suspected to be related to venlafaxine. Wheezing improved slightly after discontinuation of venlafaxine and treatment in the respiratory ICU. However, the patient could not tolerate the ICU environment, therefore became agitated, irritable, and anxious. Finally the patient gave up treatment and was discharged. Three months after discharge, the patient died of a sudden of interstitial pneumonia. A Naranjo assessment score of 3 was obtained, indicating a possible correlation between the patient's adverse drug reaction and the suspect drug.
Topics: Male; Humans; Aged; Venlafaxine Hydrochloride; Lung Diseases, Interstitial; Lung; Duloxetine Hydrochloride; Tomography, X-Ray Computed
PubMed: 37969093
DOI: 10.5414/CP204459 -
Journal of Clinical Psychopharmacology
Topics: Humans; Venlafaxine Hydrochloride; Antidepressive Agents; Seizures; Rhabdomyolysis; Hypoglycemia
PubMed: 37930213
DOI: 10.1097/JCP.0000000000001757 -
Journal of Clinical PsychopharmacologySince insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific.
METHODS
This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks).
RESULTS
EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome.
CONCLUSIONS
Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.
Topics: Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Psychotic Disorders; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 37930199
DOI: 10.1097/JCP.0000000000001756 -
The Journal of Emergency Medicine Jan 2024
Topics: Humans; Venlafaxine Hydrochloride; Antidepressive Agents; Seizures; Drug Overdose; Electrocardiography
PubMed: 37891066
DOI: 10.1016/j.jemermed.2023.07.003 -
Warmer temperature overrides the effects of antidepressants on amphibian metamorphosis and behavior.Environmental Science and Pollution... Nov 2023Climate change can exacerbate the effects of environmental pollutants on aquatic organisms. Pollutants such as human antidepressants released from wastewater treatment...
Climate change can exacerbate the effects of environmental pollutants on aquatic organisms. Pollutants such as human antidepressants released from wastewater treatment plants have been shown to impact life-history traits of amphibians. We exposed tadpoles of the wood frog Lithobates sylvaticus to two temperatures (20 °C and 25 °C) and two antidepressants (fluoxetine and venlafaxine), and measured timing of metamorphosis, mass at metamorphosis, and two behaviors (startle response and percent motionless). Antidepressants significantly shortened time to metamorphosis at 20 °C, but not at 25 °C. At 25 °C, tadpoles metamorphosed significantly faster than those at 20 °C independent of antidepressant exposure. Venlafaxine reduced body mass at 25 °C, but not at 20 °C. Temperature and antidepressant exposure affected the percent of tadpoles showing a startle response. Tadpoles at 20 °C displayed significantly more responses than at 25 °C. Exposure to fluoxetine also increased the percent of tadpoles showing a startle response. Venlafaxine reduced the percent of motionless tadpoles at 25 °C but not at 20 °C. While our results showed that antidepressants can affect the timing of metamorphosis in tadpoles, warmer temperatures overrode these effects and caused a reduction in an important reaction behavior (startle response). Future studies should address how warmer global temperatures may exacerbate or negate the effects of environmental pollutants.
Topics: Animals; Humans; Temperature; Venlafaxine Hydrochloride; Fluoxetine; Ranidae; Larva; Metamorphosis, Biological; Antidepressive Agents; Environmental Pollutants
PubMed: 37880404
DOI: 10.1007/s11356-023-30607-4 -
The Science of the Total Environment Jan 2024Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active... (Review)
Review
Mixture effects of pharmaceuticals carbamazepine, diclofenac and venlafaxine on Mytilus galloprovincialis mussel probed by metabolomics and proteogenomics combined approach.
Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active compounds (PhACs) on non-target organisms. However, not taking the co-occurrence of contaminants in the environment and their possible interactions into account may lead to underestimation of their impacts. In this study, we combined untargeted metabolomics and proteogenomics approaches to assess the mixture effects of diclofenac, carbamazepine and venlafaxine on marine mussels (Mytilus galloprovincialis). Our multi-omics approach and data fusion strategy highlighted how such xenobiotic cocktails induce important cellular changes that can be harmful to marine bivalves. This response is mainly characterized by energy metabolism disruption, fatty acid degradation, protein synthesis and degradation, and the induction of endoplasmic reticulum stress and oxidative stress. The known MeOAs and molecular signatures of PhACs were taken into consideration to gain insight into the mixture effects, thereby revealing a potential additive effect. Multi-omics approaches on mussels as sentinels offer a comprehensive overview of molecular and cellular responses triggered by exposure to contaminant mixtures, even at environmental concentrations.
Topics: Animals; Mytilus; Diclofenac; Venlafaxine Hydrochloride; Proteogenomics; Water Pollutants, Chemical; Carbamazepine; Benzodiazepines; Pharmaceutical Preparations
PubMed: 37879482
DOI: 10.1016/j.scitotenv.2023.168015 -
The Science of the Total Environment Jan 2024Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively...
Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively investigated in raised beds in which either a mixture of vegetables or maize was grown. The beds were either irrigated with treated wastewater or enriched with sewage sludge or composted sewage sludge. Over the year, samples of wastewater, water drained from the beds, soils and plants were analyzed. Of the seventy-five analyzed substances, fifty-four, thirty-three and twenty-seven were quantified in wastewater, sewage sludge, and composted sludge, respectively. Alarmingly, approximately 20 % of the compounds from wastewater were also detected in the solutions leached from the beds irrigated with wastewater (e.g., gabapentin, tramadol, sertraline, carbamazepine, its metabolites, and benzotriazoles). In addition, a gradual increase in the content of four substances (telmisartan, venlafaxine, carbamazepine, citalopram) was recorded in these beds. The compounds from both biosolids used for soil enrichment tended to remain in the soils (e.g., telmisartan, venlafaxine, sertraline, its metabolite, citalopram, and its metabolite). Only four compounds (sertraline and three benzotriazoles) leached from these beds. Uptake of some chemicals (e.g., gabapentin, tramadol, carbamazepine and its metabolite, and venlafaxine and its metabolite) and their accumulation in plant tissues was observed mainly in vegetables grown on beds irrigated with wastewater. However, daily consumption values for edible plant parts and individual compounds did not indicate a direct threat to human health. Results of this innovative study show possible risks associated with the use of these resources in agriculture. Of particular concern is the possible micropollutants percolation towards groundwater, including those for which high sorption and thus low mobility in the soil environment is expected, such as sertraline. Soil and crop contamination cannot be neglected either.
Topics: Humans; Wastewater; Sewage; Soil; Water; Citalopram; Gabapentin; Sertraline; Telmisartan; Tramadol; Venlafaxine Hydrochloride; Soil Pollutants; Vegetables; Carbamazepine
PubMed: 37866592
DOI: 10.1016/j.scitotenv.2023.167965