Antidepressant Research Articles

A randomised, open-label, pragmatic pilot comparison of oral and intravenous ketamine in treatment-resistant depression

BackgroundFor depression, ketamine is more conveniently administered by oral than by intravenous (iv) routes. The relative antidepressant efficacy of oral vs iv ketamine is unknown. ObjectivesTo assess the acute efficacy and the persistence of improvement with open-label oral versus iv ketamine in outpatients with treatment-resistant depression (TRD). MethodsAdults with TRD were randomized to oral (N=30) or IV (N=31) ketamine. Oral ketamine was dosed at 150 mg in 50 mL of water, sipped across 15 min. IV ketamine was dosed at 0.5 mg/kg, infused across 40 min. Ketamine sessions (total, 7) were administered on alternate days for 2 weeks. Ongoing antidepressant drugs were continued unchanged. Patients were assessed at baseline, day 14, and day 30. The primary outcome was the endpoint Hamilton Rating Scale for Depression score on day 14. Secondary outcomes were endpoint scores on the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression-Severity of Illness and Improvement. ResultsOverall dropout was lower with oral than with iv ketamine (26.7 % vs 54.8 %; P=0.03). The 2 groups did not differ in depression ratings and in response and remission rates on all instruments on both days 14 and 30. Adverse events such as headache (56.7 % vs 74.2 %) and drowsiness (0.0 % vs 22.6 %) were less common with oral ketamine. ConclusionIn TRD outpatients treated in general hospitals, oral ketamine maybe better accepted and tolerated than iv ketamine. Conclusions about relative efficacy cannot be drawn because of the high dropout rate with iv ketamine.

Interaction between antidepressant drug trazodone with double-stranded DNA: Multi-spectroscopic and computational analysis

Trazodone (TZD) is an antidepressant drug used to treat major depressive and sleeping disorders. Elevated doses of trazodone are associated with central nervous system depression, which manifests as nausea, drowsiness, confusion, vertigo, exhaustion, etc. To develop a clinically viable active pharmaceutical compound with minimal adverse effects, it is imperative to possess a comprehensive knowledge of the drug's action mechanism on DNA. Hence, we investigate the mode of interaction between trazodone and DNA utilizing various spectroscopic and computational techniques. Studies using UV–vis titration showed that the DNA and trazodone have an effective interaction. The magnitude of the Stern-Volmer constant (KSV) has been calculated to be 5.84 × 106 M−1 by the Lehrer equation from a steady-state fluorescence study. UV–vis absorption, DNA melting, dye displacement, and circular dichroism studies suggested that trazodone binds with DNA in minor grooves. Molecular docking and molecular dynamic simulation demonstrated that the TZD-DNA system was stable, and the mode of binding was minor groove. Furthermore, ionic strength investigation demonstrates that DNA and trazodone do not have a substantial electrostatic binding interaction.

A novel antidepressant homogeneous polysaccharide YLP-1 from Millettia pulchra ameliorates tryptophan metabolism and SCFAs through modulating gut microbiota

The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.

Clinical high risk for psychosis and service disengagement: Incidence and predictors across 2 years of follow-up.

Since there are few studies on this topic, the goals of this examination were: (1) to calculate service disengagement rates in a CHR-P sample along 2-years of follow-up; and (2) to examine the most relevant predictive factors of disengagement at baseline. All young CHR-P participants were enrolled within the 'Parma At-Risk Mental States' (PARMS) protocol. At entry, the Global Assessment of Functioning (GAF) scale and the positive and negative syndrome scale (PANSS) were completed. Cox regression analyses were used. Hundred and eighty CHR-P subjects were recruited in this examination. During the follow-up, a 2-year service disengagement prevalence rate of 15% was observed. A statistically robust predictive factor of service disengagement was a lower prescription of antidepressant drug at entry. Other relevant baseline predictive factors were migrant status, higher GAF score, lower levels of anxious-depressive symptoms and a lower acceptance of psychosocial interventions. Baseline presence of anxious-depressive features in CHR-P individuals could favour engagement to specialized EIP services. However, implementing strategies to improve patients' motivation and involvement in care are needed.

Common polygenic variation in the early medication change (EMC) cohort affects disorder risk, but not the antidepressant treatment response

BackgroundGiven the great interest in identifying reliable predictors of the response to antidepressant drugs, the present study investigated whether polygenic scores (PGS) for Major Depressive Disorder (MDD) and antidepressant treatment response (ADR) were related to the complex trait of antidepressant response in the Early Medication Change (EMC) cohort. MethodsIn this secondary analysis of the EMC trial (N = 889), 481 MDD patients were included and compared to controls from a population-based cohort. Patients were treated over eight weeks within a pre-defined treatment-algorithm. We investigated patients' genetic variation associated with MDD and ADR, using PGS and examined the association of PGS with treatment outcomes (early improvement, response, remission). Additionally, the influence of two cytochrome P450 drug-metabolizing enzymes (CYP2C19, CYP2D6) was determined. ResultsPGS for MDD was significantly associated with disorder status (NkR2 = 2.48 %, p < 1*10−12), with higher genetic burden in EMC patients compared to controls. The PGS for ADR did not explain remission status. The PGS for MDD and ADR were also not associated with treatment outcomes. In addition, there were no effects of common CYP450 gene variants on ADR. LimitationsThe study was limited by variability in the outcome parameters due to differences in treatment and insufficient sample size in the used ADR genome-wide association study (GWAS). ConclusionsThe present study confirms a polygenic contribution to MDD burden in the EMC patients. Larger GWAS with homogeneity in antidepressant treatments are needed to explore the genetic variation associated with ADR and realize the potential of PGS to contribute to specific response subtypes.

Biological Applications, In Vitro Cytotoxicity, Cellular Uptake, and Apoptotic Pathway Studies Induced by Ternary Cu (II) Complexes Involving Triflupromazine with Biorelevant Ligands.

The novel mixed-ligand complexes derived from the parent antidepressant phenothiazine drug triflupromazine (TFP) were synthesized along with the secondary ligands glycine and histidine. [Cu(TFP)(Gly)Cl]·2H2O (1) and [Cu(TFP)(His)Cl]·2H2O (2) were examined for their in vitro biological properties. Cyclic voltammetry was used to study the binding of both complexes to CT-DNA. The two complexes were examined for antiviral, antiparasite, and anti-inflammatory applications. An in vitro cytotoxicity study on two different cancer cell lines, MCF-7, HepG2, and a normal cell line, HSF, shows promising selective cytotoxicity for cancer cells. An investigation of the cell cycle and apoptosis rates was evaluated by flow cytometry with Annexin V-FITC/Propidium Iodide (PI) staining of the treated cells. Gene expression and western blotting were carried out to determine the expression levels of the pro-apoptotic markers and the anti-apoptotic marker Bcl2. The tested complexes decreased cell viability and triggered apoptosis in human tumor cell lines. Molecular docking was also used to simulate Bcl2 inhibition. Finally, complex (2) has potent antitumor effects on human tumor cells, especially against HepG2 cells, as seen in the cellular drug uptake assay. Consequently, complex (2) may prove useful against cancer, especially liver cancer. For further understanding, it needs to be explored in vivo.

Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST). Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs. The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo. Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions

(R,S)-ketamine (ketamine) has rapid and sustained antidepressant (AD) efficacy at sub-anesthetic doses in depressed patients. A metabolite of ketamine, including (2R,6R)-hydroxynorketamine ((6)-HNKs) has been reported to exert antidepressant actions in rodent model of anxiety/depression. To further understand the specific role of ketamine's metabolism in the AD actions of the drug, we evaluated the effects of inhibiting hepatic cytochrome P450 enzymes on AD responses. We assessed whether pre-treatment with fluconazole (10 and 20 mg/kg, i. p.) 1 h prior to ketamine or HNKs (10 mg/kg, i. p.) administration would alter behavioral and neurochemical actions of the drugs in male BALB/cJ mice with a highly anxious phenotype. Extracellular microdialysate levels of glutamate and GABA (Gluext, GABAext) were also measured in the medial prefrontal cortex (mPFC). Pre-treatment with fluconazole altered the pharmacokinetic profile of ketamine, by increasing both plasma and brain levels of ketamine and (R,S)-norketamine, while robustly reducing those of (6)-HNKs. At 24 h post-injection (t24 h), fluconazole prevented the sustained AD-like response of ketamine responses in the forced swim test and splash test, as well as the enhanced cortical GABA levels produced by ketamine. A single (2R,6R)-HNK administration resulted in prevention of the effects of fluconazole on the antidepressant-like activity of ketamine in mice. Overall, these findings are consistent with an essential contribution of (6)-HNK to the sustained antidepressant-like effects of ketamine and suggest potential interactions between pharmacological CYPIs and ketamine during antidepressant treatment in patients.

Impact of the COVID-19 pandemic on antidepressant consumption in the Central region of Portugal: interrupted time series.

To evaluate the impact of the pandemic on the consumption of antidepressive agents in Central Portugal. To estimate the causal effect of the pandemic an interrupted time series analysis was conducted. Data of antidepressant drugs monthly dispensed in community pharmacies between Jan-2010 and Dec-2021 were provided by the regional Health Administration. Anti-Parkinson dopaminergic agents and statins, theoretically not influenced by COVID-19 pandemics, were used as comparator series. The number of packages was converted into defined daily doses and presented as defined daily doses/1000 inhabitants/day. A Bayesian structural time-series model with CausalImpact on R/RStudio was used to predict the counterfactual. Analyses with different geographical granularity (9 sub-regions and 78 municipalities) were performed. When compared to counterfactual, regional consumption non-significantly increased after the pandemic declaration, with a relative effect of + 1.30% [95%CI -1.6%:4.2%]. When increasing the granularity, differences appeared between sub-region with significant increases in Baixo Mondego + 6.5% [1.4%:11.0%], Guarda + 4.4% [1.1%:7.7%] or Cova da Beira + 4.1% [0.17%:8.3%], but non-significant variation in the remaining 6 sub-regions. Differences are more obvious at municipality level, ranging from increases of + 37.00% [32.00%:42.00%] to decreases of -11.00% [-17.00%:-4.20%]. Relative impact positively correlated with percentage of elderly in the municipality (r = 0.301; p = 0.007), and negatively with population density (r=-0.243; p = 0.032). No other predicting variables were found. Antidepressant consumption suffered very slight variations at regional level after the COVID-19 pandemic declaration. Analysis with higher granularity allowed identifying municipalities with higher impact (increase or decrease). The absence of clear association patterns suggests other causal hypotheses of the differences.

Nitric Oxide Donor Sodium Nitroprusside Reduces Racemic Ketamine-But Not Esketamine-Induced Pain Relief.

The anesthetic, analgesic and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.min-1 SNP or placebo during a 3-h infusion of escalating doses of racemic ketamine (total dose 140 mg) or esketamine (70 mg). Pain pressure threshold (PPT) and arterial blood samples for measurement of S- and R-ketamine and their metabolites, S- and R-norketamine, were obtained. The data were analyzed with a population pharmacokinetic-pharmacodynamic model that incorporated the measured S- and R- ketamine and S- and R-norketamine isomers as input and PPT as output to the model. The potency of the 2 formulations in increasing PPT from baseline by 100% was 0.47 ± 0.12 (median ± standard error of the estimate) nmol/mL for esketamine and 0.62 ± 0.19 nmol/mL for racemic ketamine, reflecting the 52 ± 27% lower analgesic potency of R-ketamine versus S-ketamine. Modeling showed that SNP had no effect on S-ketamine potency but abolished the R-ketamine analgesic effect. Similar observations were made for S- and R-norketamine. Since SNP had no effect on S-ketamine analgesia, we conclude that SNP interacts on R-ketamine nociceptive pathways, possibly similar to its effects on R-ketamine activated dissociation pathways.

Evaluating drug withdrawal syndrome risks through food and drug administration adverse event reporting system: a comprehensive disproportionality analysis.

The study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome. All the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome. A total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs. Our analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications.

Antidepressant and antipsychotic prescribing in patients with type 2 diabetes in Scotland: A time-trend analysis from 2004 to 2021.

Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. We conducted repeated annual cross-sectional analysesof a population-based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross-sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person-years to 33.3 per 100 person-years and from 2.8 per 100 person-years to 4.7 per 100 person-years, respectively). We observed this pattern for all drug subtypes except for first-generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration.

Antidepressant drug use after intensive care: a nationwide cohort study

Modern intensive care has improved survival rates, but emerging evidence suggests a high prevalence of post-intensive care unit (ICU) health problems, including post-traumatic stress disorder, depression and anxiety. These symptoms may have a detrimental effect on quality of life and increase mortality. The primary objective of this study is to examine the extent of initiation of antidepressant medication among ICU survivors and identify the factors associated with its usage. The secondary objective is to investigate whether the use of these medications is linked to an increased mortality. The nationwide study cohort included 125,130 ICU survivors admitted between 2010 and 2017. Within the first 3 months after ICU discharge, 7% of patients initiated antidepressant medication, by 1 year 15.5% had started medication. We found no tendency to a decrease during the 2-year follow-up period. Factors associated with antidepressant use included middle age, female sex, psychiatric and somatic comorbid conditions, substance dependence, higher illness severity, and longer ICU stay. Antidepressant users had a higher mortality rate, and deaths due to external causes and suicide were more frequent in this group. This study emphasizes the importance of detecting and addressing depression in ICU survivors to improve their quality of life and reduce mortality rates.

In-person psychoeducational intervention to reduce rehospitalizations and improve the clinical course of major depressive disorder: a non-randomized pilot study.

Emerging issues in the management of major depressive disorder (MDD) comprise a nonadherence to treatment and treatment failures, depressive recurrence and relapses, misidentification of incoming exacerbated phases and consequently, a chronification of depression. While antidepressant drugs constitute the standard of care for MDD, effective psychosocial interventions are needed to reduce rehospitalizations and other adverse events. The present study primarily investigated the effects and impact of implementing a structured psychoeducational intervention on the clinical course of MDD. A non-randomized comparative, pragmatic, pilot, single-center study of adults with nonpsychotic moderate or severe episode of MDD recently discharged from a psychiatric hospitalization. The consecutive subjects were allocated either to the intervention group (N=49) or to the attention control group (N=47), based on their preference. The psychoeducational intervention was based on a modified Munoz's Depression Prevention Course. Subjects were followed up prospectively for two years. The absolute changes in Beck anxiety inventory scale, Zung's depression questionnaire, and Montgomery and Äsberg depression rating scale (MADRS) total scores at 6-month follow-up were comparable between the two groups. There were lower rates of the rehospitalization within one year (2.1% vs. 16.7%; P<0.001) and less rehospitalizations after one year (6.3% vs. 25%; P<0.001), lower rates of the ongoing sickness absence (11.5% vs. 29.2%; P<0.001), less persons with disability due to MDD at 1-year follow-up (1% vs. 11.5%; P=0.002), and less nonadherent subjects who self-discontinued treatment (6.3% vs. 28.1%; P<0.001) among participants in the intervention group compared to the control group. The disability due to MDD at 1-year follow-up was predicted by the absence of the psychoeducational intervention (P=0.002) and by the MADRS total score at 6-month follow-up (OR 1.10; 95% CI 1.003-1.195; P=0.044). Qualitative data indicated the intervention was desired and appreciated by the participants, as well as being practical to implement in Slovakian clinical settings. The results suggest the psychoeducational intervention based on a modified Munoz's Depression Prevention Course has beneficial effects in adults with MDD recently discharged from a psychiatric hospitalization. The findings implicate the psychoeducational intervention may offer a new approach to the prevention of depressive relapses.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P&amp;lt;0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P&amp;lt;0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

Association between previous SARs-CoV-2 infection and new prescription of antidepressant drugs: a case-control study in Friuli Venezia Giulia region, Italy.

A rise in affective and anxiety disorders and in antidepressant (AD) treatment during the COVID-19 pandemic has been extensively described, but few studies were provided at the individual level, further considering COVID-19 severity and vaccination status. Case-control study evaluating the association between the new use of ADs and a previous COVID-19 infection, in Friuli Venezia Giulia Region, Italy, from March 1, 2020, to July 19, 2022. Multiple conditional logistic regressions assess the association between a new AD use and a COVID-19 infection previous to the index date, stratified by gender, age and anti-COVID-19 vaccination status. Odds Ratios (OR) and 95% confidence intervals were reported. COVID-19 was associated with AD treatment after the infection. The disease severity was positively associated with a growing risk of being dispensed an AD, with the highest risk in unvaccinated subjects previously hospitalised in ICU (OR = 28.77). The risk of using ADs after COVID-19 infection was higher in unvaccinated subjects aged 65 years and older, both females and males. The association between COVID-19 infection and AD dispensation in vaccinated subjects was not significant, with the exception of females aged 65 years and over. Anti-COVID-19 vaccination, especially among the elderly, might prevent post-COVID AD treatment. Clinicians should be aware that COVID-19 patients requiring hospitalisation are more likely to experience these symptoms, given their higher risk of being dispensed ADs. Future studies may benefit by analysing the incidence of both mental disorders and psychotropic treatment in post-COVID patients, considering socioeconomic factors and vaccination status.

Dyslipidemia among psychiatric patients with depression – common possible reasons and treatment implications – review

Dyslipidemia is a medical term used to describe an abnormal level of lipids (fats) in the blood. This can include elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high density protein lipoprotein (HDL) cholesterol and serum triglicerides. Depression, also known as depressive disorder, is a common mental illness. It is characterized by a persistent feeling of sadness, loss of pleasure, or lack of interest in activities that are present of at least two weeks and significantly impair patient everyday functioning. Dyslipidemia and depression can co-occur due to a complex interplay of shared risk factors, such as inflammation, metabolic syndrome, medication side effects, and lifestyle changes, suggesting a bidirectional relationship where each condition might contribute to the development or exacerbation of the other. Given these considerations, a comprehensive approach to managing dyslipidemia in psychiatric patients with depression is essential. This should include regular monitoring of lipid profiles and monitoring of anticholesterol and antidepressant drugs. Interestingly, simple lifestyle changes, such as a healthy diet and exercise, have an impact on the treatment of depression and dyslipidemia.

Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators.

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection against OS-related cellular damage; notably, the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates Nrf2 and promotes its nuclear translocation. However, insufficient neurotrophin support often leads to the downregulation of the TrkB signaling pathway in brain diseases. Thus, targeting TrkB activation and the Nrf2-ARE system is a promising therapeutic strategy for treating neurodegenerative diseases. Phytochemicals, including indole-3-carbinol (I3C) and its metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF's mimetic activity; Akt phosphorylation is induced, and the antioxidant defense mechanism is activated by blocking the Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes the therapeutic potential of I3C and its derivatives for concurrently activating neuronal defense mechanisms in the treatment of neurodegenerative diseases.

Acute treatment of bilateral rTMS combined with antidepressants on the plasma fatty acids for major depressive episodes

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.

Antidepressant drug against bacterial pathogens: Effect of citalopram on biofilm forming hospital-acquired infectious (HAIs) agents

Antidepressant drug against bacterial pathogens: Effect of citalopram on biofilm forming hospital-acquired infectious (HAIs) agents