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Frontiers in Pharmacology 2024Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the...
Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly , , and ; the top three treatments on the reduction of HAMD scores were , , and ; and the top three treatments with the lowest adverse effects rates were , , and . Interestingly, commonly used synthetic drugs such as , , , , , and , not only appeared to be less effective than specific Chinese herbal medicines (, , , , and ), but they were also related to substantially higher risk of adverse events. Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.
PubMed: 38633609
DOI: 10.3389/fphar.2024.1295564 -
Current Molecular Pharmacology 2024Diabetic mellitus is responsible for triggering many conditions, such as neuropathy, nephropathy, and retinopathy. Hyperglycemia leads to the development of oxidative... (Review)
Review
BACKGROUND
Diabetic mellitus is responsible for triggering many conditions, such as neuropathy, nephropathy, and retinopathy. Hyperglycemia leads to the development of oxidative stress conditions, activation of pathways, and generation of metabolites, leading to complications like neuropathy and nephropathy.
OBJECTIVE
This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.
METHODS
Research works were searched from international and national databases with keywords like "diabetes," "diabetic nephropathy," "NADPH," "oxidative stress," "PKC," "Molecular mechanisms," " cellular mechanisms," "complications of diabetes," and "factors." The databases searched were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.
RESULTS
Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic nephropathy. Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications, including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate. Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of neuroinflammation, NF-κB, AP-1, etc. Conclusion: Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.
Topics: Humans; Diabetic Neuropathies; Diabetic Nephropathies; Neuroinflammatory Diseases; Oxidative Stress; Antidepressive Agents; Diabetes Mellitus
PubMed: 37018534
DOI: 10.2174/1874467217666230328084215 -
The Science of the Total Environment Sep 2023Emerging contaminants and their pervasive presence in freshwater ecosystems have been widely documented, but less is known about their prevalence and the harm they cause...
Contaminants and their ecological risk assessment in beach sediments and water along the Maharashtra coast of India: A comprehensive approach using microplastics, heavy metal(loid)s, pharmaceuticals, personal care products and plasticisers.
Emerging contaminants and their pervasive presence in freshwater ecosystems have been widely documented, but less is known about their prevalence and the harm they cause in marine ecosystems, particularly in developing countries. This study provides data on the prevalence and risk posed by microplastics, plasticisers, pharmaceuticals and personal care products (PPCPs), and heavy metal(loid)s (HMs) along the Maharashtra coast of India. The sediment and coastal water samples were collected from 17 sampling stations, processed, and subjected to FTIR-ATR, ICP-MS, SEM-EDX, LC-MS/MS, and GC-MS for further analysis. Higher MPs abundance, combined with the pollution load index, indicates that the northern zone is a high-impact zone with pollution concerns. Plasticisers in extracted MPs and HMs adsorption on MPs surface from surrounding waters reveal their roles as a source and vector for contaminants, respectively. The mean concentration of metoprolol (53.7-306 ng L), tramadol (16.6-198 ng L), venlafaxine (24.6-234 ng L), and triclosan (211-433 ng L) in Maharashtra's coastal waters were several folds higher than in other water systems, raising major health concerns. The hazard quotient (HQ) scores revealed that >70 % of study sites pose a high to medium (1 > HQ > 0.1) ecological risk to fish, crustaceans and algae, indicating serious concern. Fish and crustaceans (35.3 % each) show a higher level of risk than algae (29.5 %). Metoprolol and venlafaxine could represent greater ecological risks than tramadol. Similarly, HQ suggests that bisphenol A has larger ecological risks than bisphenol S along the Maharashtra coast. To the best of our knowledge, this is the first in-depth investigation into emerging pollutants in Indian coastal regions. This information is crucial for better policy formulation and coastal management in India in general, and Maharashtra in particular.
Topics: Animals; Microplastics; Ecosystem; Water; Plastics; Geologic Sediments; Chromatography, Liquid; Metoprolol; Tramadol; Venlafaxine Hydrochloride; Water Pollutants, Chemical; India; Tandem Mass Spectrometry; Metals, Heavy; Risk Assessment; Cosmetics; Pharmaceutical Preparations; Environmental Monitoring
PubMed: 37301381
DOI: 10.1016/j.scitotenv.2023.164712 -
Archives of Pharmacal Research May 2024Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is indicated for the treatment of major depressive disorder, social anxiety disorder, generalized...
PBPK modeling to predict the pharmacokinetics of venlafaxine and its active metabolite in different CYP2D6 genotypes and drug-drug interactions with clarithromycin and paroxetine.
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is indicated for the treatment of major depressive disorder, social anxiety disorder, generalized anxiety disorder, and panic disorder. Venlafaxine is metabolized to the active metabolite desvenlafaxine mainly by CYP2D6. Genetic polymorphism of CYP2D6 and coadministration with other medications can significantly affect the pharmacokinetics and/or pharmacodynamics of venlafaxine and its active metabolite. This study aimed to establish the PBPK models of venlafaxine and its active metabolite related to CYP2D6 genetic polymorphism and to predict drug-drug interactions (DDIs) with clarithromycin and paroxetine in different CYP2D6 genotypes. Clinical pharmacogenomic data for venlafaxine and desvenlafaxine were collected to build the PBPK model. Physicochemical and absorption, distribution, metabolism, and excretion (ADME) characteristics of respective compounds were obtained from previously reported data, predicted by the PK-Sim software, or optimized to capture the plasma concentration-time profiles. Model evaluation was performed by comparing the predicted pharmacokinetic parameters and plasma concentration-time profiles to the observed data. Predicted plasma concentration-time profiles of venlafaxine and its active metabolite were visually similar to the observed profiles and all predicted AUC and C values for respective compounds were included in the twofold error range of observed values in non-genotyped populations and different CYP2D6 genotypes. When clarithromycin or clarithromycin plus paroxetine was concomitantly administered, predicted plasma concentration-time profiles of venlafaxine properly captured the observed profiles in two different CYP2D6 genotypes and all predicted DDI ratios for AUC and C were included within the acceptance range. Consequently, the present model successfully captured the pharmacokinetic alterations of venlafaxine and its active metabolite according to CYP2D6 genetic polymorphism as well as the DDIs between venlafaxine and two CYP inhibitors. The present model can be used to predict the pharmacokinetics of venlafaxine and its active metabolite considering different races, ages, coadministered drugs, and CYP2D6 activity of individuals and it can contribute to individualized pharmacotherapy of venlafaxine.
Topics: Venlafaxine Hydrochloride; Clarithromycin; Humans; Cytochrome P-450 CYP2D6; Drug Interactions; Paroxetine; Genotype; Models, Biological; Adult; Male; Serotonin and Noradrenaline Reuptake Inhibitors; Female; Polymorphism, Genetic; Young Adult
PubMed: 38664354
DOI: 10.1007/s12272-024-01495-0 -
European Journal of Pharmaceutical... Dec 2023Intrinsic membrane permeability is one of several factors that critically determine the intestinal absorption of a chemical. The intrinsic membrane permeability of a...
Intrinsic membrane permeability is one of several factors that critically determine the intestinal absorption of a chemical. The intrinsic membrane permeability of a chemical is usually extracted from transwell experiments with Caco-2 or MDCK cells, preferably by the pK-Flux method, which is considered the method of choice when aqueous boundary layer effects need to be excluded. The pK-Flux method has two variants, the iso-pH method, where apical and basolateral pH are equal, and the gradient-pH method, where apical and basolateral pH are different. The most commonly used method is the gradient-pH method, as it is intended to reflect the pH-conditions in the gastrointestinal tract. However, concentration-shift effects caused by the applied pH-difference between apical and basolateral compartment in the gradient-pH method have not been considered in the evaluation of the experimental data in the past. Consequently, incorrect intrinsic membrane permeabilities have been determined. In this work, we present a revised method for extracting the intrinsic membrane permeability from gradient-pH data that considers concentration-shift effects in the basolateral aqueous boundary layer and filter as well as in the cytosol. Furthermore, we propose the use of the iso-pH method, where only concentration-shift effects in the cytosol need to be considered, as an alternative to the gradient-pH method. We use the five lipophilic bases amantadine, chloroquine, propranolol, venlafaxine and verapamil as examples to compare gradient-pH method and iso-pH method with regard to the extractability of the intrinsic membrane permeability. For lipophilic bases, the iso-pH method proves to be advantageous. All intrinsic membrane permeabilities determined in this work were substantially higher than the intrinsic membrane permeabilities reported in literature.
Topics: Humans; Caco-2 Cells; Cell Membrane Permeability; Propranolol; Intestinal Absorption; Permeability; Hydrogen-Ion Concentration
PubMed: 37751809
DOI: 10.1016/j.ejps.2023.106592 -
BMC Complementary Medicine and Therapies Oct 2023Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple...
BACKGROUND
Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies indicated that pharmacological option such as venlafaxine provides partial relief, but the tolerability is poor when dose is not tapered. Hence, alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence.
METHODS
Five hospitals will recruit 120 acupuncture naïve patients with moderate-to-severe hot flashes after prostate cancer received ADT in China from February 2023 to December 2024. Participants will be randomly 2:1:1 allocated to the 18 sessions of verum acupuncture at true acupuncture points plus usual care, 18 sessions of non-penetrating sham acupuncture at non-acupuncture points plus usual care, or usual care alone over 6 weeks. The primary outcome measure is the change of mean weekly hot flashes symptom severity score (HFSSS) at the end of treatment compared with baseline.
EXPECTED RESULTS AND CONCLUSION
We will be able to measure the effectiveness of acupuncture for patients with PCa suffering from ADT-induced hot flashes and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients.
TRIAL REGISTRATION
Clinicaltrials.gov (NCT05069467).
Topics: Male; Humans; Hot Flashes; Androgen Antagonists; Prostatic Neoplasms; Acupuncture Therapy; Acupuncture Points; Randomized Controlled Trials as Topic
PubMed: 37891531
DOI: 10.1186/s12906-023-04218-y -
International Journal of Psychiatry in... Mar 2024This study aimed to explore male-female differences in suicide ideation (SI) and suicide risk factors in major depressive disorder (MDD).
OBJECTIVE
This study aimed to explore male-female differences in suicide ideation (SI) and suicide risk factors in major depressive disorder (MDD).
METHODS
We analysed 482 adults (sample 1) and 438 elderly outpatients (sample 2) with MDD. Sample 1 was treated with different antidepressant combinations (escitalopram; bupropion plus escitalopram; venlafaxine plus mirtazapine) and assessed by means of the Concise Health Risk Tracking (SI), Quick Inventory of Depressive Symptomatology, Altman Mania Rating Scale and Psychiatric Diagnostic Screening Questionnaire. Sample 2 was treated with venlafaxine and assessed using the Hamilton scale for depression, Anxiety Sensitivity Index and Penn State Worry Questionnaire for anxiety, Beck Scale for Suicide Ideation and Repeatable Battery for the Assessment of Neuropsychological Status.
RESULTS
In sample 1, females had greater depression severity (O.R 0.961 99%CI: 0.929 - 0.995), males reported more alcohol abuse (O.R 1.299 99%CI: 1.118 - 1.509) and active SI (O.R 1.109 99%CI: 1.005 - 1.255). In sample 2 men showed more severe SI (O.R 1.067; 99%CI: 1.014 - 1.122) and weight loss (OR = 5.89 99%CI: 1.01 - 34.19), women more gastrointestinal symptoms.
CONCLUSIONS
In these selected samples, although women had more severe depression, men had more suicide risk factors. Such differences might contribute to men's increased suicide risk.
Topics: Humans; Depressive Disorder, Major; Female; Male; Suicidal Ideation; Adult; Middle Aged; Aged; Sex Factors; Venlafaxine Hydrochloride; Antidepressive Agents; Severity of Illness Index; Citalopram; Young Adult; Bupropion; Risk Factors
PubMed: 38587055
DOI: 10.1080/13651501.2024.2335950 -
International Journal of Molecular... May 2024Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to...
Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group ( < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine ( < 0.05 central zone; ≤ 0.05 periphery zone) and SMe1EC2M3 ( < 0.05 central zone; < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST ( < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group ( < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group ( < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.
Topics: Animals; Rats; Male; Disease Models, Animal; Antidepressive Agents; Venlafaxine Hydrochloride; Depression; Behavior, Animal; Depressive Disorder, Treatment-Resistant; Rats, Inbred WKY; Stress, Psychological; Anxiety; Indoles; Anhedonia
PubMed: 38791304
DOI: 10.3390/ijms25105265 -
Journal of Pharmacy & Bioallied Sciences Feb 2024Antidepressants have anti-inflammatory effects and boost immunity, and dentists should be aware. This case-control study included only those patients who consented to...
Antidepressants have anti-inflammatory effects and boost immunity, and dentists should be aware. This case-control study included only those patients who consented to take part and had a ham-d score of at least 16 and a diagnosis of moderate-to-severe depression. Inclusion criteria included adults, those experiencing moderate to severe depression, taking fluoxetine or venlafaxine, and those with twenty or more teeth. Exclusion criteria included tobacco chewers, smokers, women expecting or nursing, periodontal treatment, antibiotics, anti-inflammatory medication, or vitamin/nutritional supplements. Patients who had had surgery or other therapy were excluded from the study. Three groups of patients were created: Control, venlafaxine, and fluoxetine. A periodontist assisted in the dental examination, and indices were observed. The analysis was done using Statistical Package for the Social Sciences (SPSS) version 24.0. Number, percentage, mean, and standard deviation were used to present the values. Results showed that antidepressants may be a risk factor for periodontal health, with increased periodontal parameters, and concluded that It is crucial to frequently check the periodontal health of depressed people using fluoxetine or venlafaxine since these drugs put good periodontal tissues at risk.
PubMed: 38595612
DOI: 10.4103/jpbs.jpbs_464_23 -
The Journal of Pharmacy and Pharmacology Jan 2024Venlafaxine exposure through gestation is affected by the longitudinal changes in maternal physiology. Confounding treatment is also the impact of CYP2D6 polymorphisms...
OBJECTIVES
Venlafaxine exposure through gestation is affected by the longitudinal changes in maternal physiology. Confounding treatment is also the impact of CYP2D6 polymorphisms affecting plasma concentrations of venlafaxine.
METHODS
A pharmacokinetic modelling approach was employed to assess variations in maternal and foetal cord venlafaxine levels throughout gestation and to identify appropriate doses to maintain venlafaxine levels within the therapeutic range.
KEY FINDINGS
Throughout gestation, there was a significant decrease in simulated venlafaxine trough plasma concentrations in both extensive metaboliser (EM) and ultra-rapid metaboliser (UM) phenotypes. Approximately 70%-87% of EM and UM phenotypes exhibited trough venlafaxine plasma concentrations below the therapeutic level (<25 ng/ml), which increased to 96% at week 30. While for poor metabolizer (PM) phenotypes, the percentage was approximately 4%.
CONCLUSION
The standard daily dose of 75 mg required adjustment for all phenotypes examined during gestation. A daily dose of 37.5-112.5 mg is appropriate for PM throughout pregnancy. For EM, a dose of 225 mg daily in the first trimester, 262.5 mg daily in the second trimester, and 375 mg daily in the third trimester is suggested to be optimal. For UM, a dose of 375 mg daily throughout gestation is suggested to be optimal.
Topics: Pregnancy; Female; Humans; Venlafaxine Hydrochloride; Phenotype; Cytochrome P-450 CYP2D6; Cross-Over Studies; Polymorphism, Genetic
PubMed: 38142123
DOI: 10.1093/jpp/rgad106