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Frontiers in Psychiatry 2024Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut...
BACKGROUND
Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear.
METHODS
Male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment.
RESULTS
CPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of and in CPZ-treated mice.
CONCLUSION
The anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.
PubMed: 38899045
DOI: 10.3389/fpsyt.2024.1347867 -
Water Research Jun 2024Wastewater treatment plants (WWTPs) are essential for maintaining a good water quality of surface waters. However, WWTPs are also associated with water quality...
Wastewater treatment plants (WWTPs) are essential for maintaining a good water quality of surface waters. However, WWTPs are also associated with water quality deterioration and hydro-morphological alteration. Riverine communities respond to these stressors with changes in their community structure, abundance and diversity. In this study, we used a dataset of 94 monitoring sites across North Rhine-Westphalia, Germany to investigate the influence of WWTPs on the water quality and hydro-morphological quality in river sections downstream of WWTP effluents. More specifically, we analyzed the effects of the percentage of WWTP effluents (in relation to median base flow) on four stressor groups (physico-chemistry, micropollutants, hydrological and morphological alteration) using Linear Mixed Models (LMM). Furthermore, we assessed the impact of a selection of twelve ecologically relevant stressor variables reflecting water quality deterioration and hydro-morphological alteration on reference fish communities using Canonical Correspondence Analysis (CCA). The percentage of WWTP effluents was correlated with water quality, especially with toxic units of a wide range of pharmaceuticals including diclofenac, venlafaxine and sulfamethoxazole (R² up to 0.54) as well as specific pesticides (e.g., terbutryn: R² = 0.33). The correlation of percent WWTP effluents with hydro-morphological alteration was weaker and most pronounced for the frequency of high flow (R² = 0.24) and flow variability (R² = 0.19). About 40 % of the variance in the fish community structure were explained by 12 stressor variables in the CCA models. Water quality and hydrological, but not morphological stressors showed strong albeit highly variable effects on individual fish species. The results indicate that water quality degradation and hydrological alteration are important factors determining the ecological status of fish communities. In this context, WWTP effluents can impose relevant point sources of pollution that affect water quality but also cause alterations of the hydrological regime. Further management measures addressing both stressor groups are needed to improve the ecological status.
PubMed: 38880012
DOI: 10.1016/j.watres.2024.121914 -
Nature and Science of Sleep 2024This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).
PURPOSE
This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).
METHODS
Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate.
RESULTS
Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time ( =0.007), decreased sleep efficiency ( =0.002), shortening of sleep onset latency ( <0.001), elevated wake after sleep onset ( =0.002), increased N1% ( =0.006), and reduced N2%, N3%, and REM% ( =0.007, <0.001, =0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity ( <0.001), and increased brain fatigue ( =0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue ( <0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue ( =0.013, =0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (=0.012, =0.030).
CONCLUSION
NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.
PubMed: 38873239
DOI: 10.2147/NSS.S452665 -
The Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0 -
Advances in Pharmacological and... 2024Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy....
INTRODUCTION
Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions.
OBJECTIVE
To investigate any potential herb-drug interaction that might exist between extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice.
METHODS
Dried, powdered fruits of were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis.
RESULTS
XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the extract/fluoxetine ( = 0.502), extract/imipramine ( = 0.322), extract/venlafaxine ( = 0.601), xylopic acid/imipramine ( = 0.556), xylopic acid/venlafaxine ( = 0.451), and xylopic acid/fluoxetine ( = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUC = 1966 ± 58.98 g/ml.h) was significantly ( < 0.0001) reduced by extract (AUC = 1228 ± 67.40 g/ml.h) and xylopic acid (AUC = 1250 ± 55.95 g/ml.h), while the AUC of xylopic acid (AUC = 968.10 ± 61.22 g/ml.h) was significantly ( < 0.0001) reduced by venlafaxine (AUC = 285.90 ± 51.92 g/ml.h) and fluoxetine (AUC = 510.60 ± 44.74 g/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption.
CONCLUSION
extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.
PubMed: 38826835
DOI: 10.1155/2024/9923801 -
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 -
The Science of the Total Environment Aug 2024Freshwater systems are facing a number of pressures due to the inputs of polar organic contaminants from a range of sources including agriculture, domestic and industry....
Freshwater systems are facing a number of pressures due to the inputs of polar organic contaminants from a range of sources including agriculture, domestic and industry. The River Itchen and River Test are two sensitive chalk streams in Southern England that are experiencing a decline in invertebrate communities. We used Chemcatcher passive samplers to measure time-weighted average concentrations (14 days) of polar pollutants at nine sites on the River Itchen and eight sites on the River Test over a 12-month period. Sampler extracts were analysed using a targeted LC/MS method. In total, 121 plant protection products and pharmaceutical and personal care products were quantified (range of log K from - 1.5 to 7). Concentrations (sub ng L to >500 ng L) in both rivers showed spatial and temporal variations. A greater number of compounds and higher concentrations were found in the River Test. The chemical profile was dominated by inputs from wastewater treatment plants and legacy plant protection products. On the River Itchen, high concentrations (∼100 ng L) of caffeine were observed directly downstream of a fish farm. Using the NORMAN database, the predicted no effect concentration (PNEC) freshwater values were exceeded by only five contaminants (2-hydroxy-terbuthylazine, alprazolam, azithromycin, diclofenac and imidacloprid). In addition, venlafaxine was detected above its EU Watch List concentration. These exceedances were mainly downstream of direct inputs from treatment plants. These compounds are known to have ecotoxicological effects on a range of aquatic biota including macroinvertebrates. Of concern is the ubiquitous presence of the ectoparasiticide imidacloprid, highlighting the need to control its use. The impact of the cocktail of pollutants found in this study on the long-term effects on chalk stream ecosystems remains unknown and needs further investigation.
Topics: Water Pollutants, Chemical; Rivers; Environmental Monitoring; Risk Assessment; England
PubMed: 38782290
DOI: 10.1016/j.scitotenv.2024.173316 -
Chemosphere Aug 2024This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces...
This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces drinking water from combination of wastewater reuse and desalination. The membrane biological reactor (MBR) exhibit removal rates exceeding 95% of pharmaceuticals like acetaminophen, trimethoprim, diclofenac, naproxen, and emtricitabine. The efficiency of brackish reverse osmosis (BWRO) in removing ECs is highlighted, showing substantial efficacy with reduction rates of 99.5%, 75.5%, and 51.2% for sulfamethoxazole, venlafaxine, and benzotriazole, respectively. The advanced oxidation process based on Fenton process reveals removal (>95%) of emtricitabine, efavirenz, and carbamazepine. The study confirms that the combination of treatment units within the RWTP effectively removes heavy metals (>90%), complying with acceptable limits. Risk quotient (RQ) calculations indicate the efficiency of the RWTP in EC removal, serving as benchmarks for public acceptance of reclaimed water. In the context of heavy metals, the study concludes negligible cancer risks associated with reclaimed water consumption over a lifetime. Quantitative structure-activity relationship and occurrence, persistence, bioaccumulation and toxicity (OPBT) models were used to assess EC risk. The study screened and identified potential persistant, bio accumulating and toxic PBT ECs. Critical control points (CCPs) in the RWTP are identified, with brackish and seawater reverse osmosis (BWRO and SWRO) and advanced oxidation process (AOP) recognized as pivotal in hazard management. The study provides valuable insights on the removal of ECs and heavy metals in a wastewater reuse process and demonstrates potential of adopted process configuration in supplying safe drinking water from wastewater recycling.
Topics: Water Pollutants, Chemical; Metals, Heavy; Wastewater; Risk Assessment; Water Purification; Drinking Water; Humans; Waste Disposal, Fluid
PubMed: 38777194
DOI: 10.1016/j.chemosphere.2024.142396 -
World Psychiatry : Official Journal of... Jun 2024Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative...
Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.
PubMed: 38727044
DOI: 10.1002/wps.21205