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Introduction and purpose: Major depressive disorder (MDD) is the most common psychiatric illness, affecting millions of people worldwide. The first line of pharmacological treatment is usually monoamine reuptake inhibitors. Up to 60% of cases, may be drug-resistant patients, prompting researchers to research substances other than conventional. 1 The purpose of this article was to review recent studies on the use of ketamine in the treatment of drug-resistant depression and present their findings. Brief description of the state of knowledge: Ketamine has been a well-known drug used in anesthesiology and pain management for decades. Because of its multidirectional effects, researchers have become interested in its effects on psychiatric illnesses. Over the past decade or so, there has been a definite increase in research and articles on the use of ketamine in psychiatry. The study has resulted in FDA approval of esketamine for the treatment of treatment-resistant depression in adults in 2019. Material and method: This article is the result of searching keywords on databases such as Google Scholar and Pubmed and collecting scientific literature about depression and ketamine. Articles were preselected by title, number of citations, source, and publication date. Summary: Ketamine has the potential to be a treatment for drug-resistant depression. Its effectiveness varies with the form and dosage, with racemic and higher doses offering greater therapeutic benefits. Ketamine's efficacy is on par with the electroconvulsive therapy. Its onset is faster than traditional antidepressants, significantly reducing suicide risk in a shorter time frame. While the precise mechanisms of its antidepressant effects are not fully understood, it is suggested that its impact on brain neuroplasticity may contribute to the rapid onset of action. Growing evidence supports ketamine's effectiveness in treating TRD, highlighting the need for further research in this area.

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4andHTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (includingBDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions. [ABSTRACT FROM PUBLISHER]

This review considers evidence for the efficacy of pharmacotherapy among primary care patients with depressive disorders and reviews knowledge regarding the effectiveness of current practice. Strong evidence supports the efficacy of antidepressant pharmacotherapy for primary care patients with major depression and dysthymia with some evidence for pharmacotherapy of less severe depression. In general, available antidepressants appear equal in both efficacy and effectiveness. Treatment selection for any individual patient remains largely empirical, with few clinical characteristics predicting better or worse response to specific treatments. Strong evidence supports continuation treatment (i.e., at least six months of pharmacotherapy) for all patients and maintenance treatment (i.e., at least 24 months of pharmacotherapy) for those with chronic or recurrent depression. Unfortunately, few patients in primary care or specialty practice receive recommended levels of pharmacotherapy or recommended frequency of follow-up care. A number of recent studies have evaluated strategies to improve the quality of antidepressant treatment in primary care. Educational programs (including academic detailing and continuous quality improvement) have had little impact on patient outcomes. Key elements of effective care improvement programs include specific, evidence-based treatment protocols, organized patient education and active follow-up care. [Copyright &y& Elsevier]

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration: ISRCTN, ISRCTN15984604. Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021. [ABSTRACT FROM AUTHOR]

Background: Evidence-based treatments for depression exist but not all patients benefit from them. Efforts to develop predictive models that can assist clinicians in allocating treatments are ongoing, but there are major issues with acquiring the volume and breadth of data needed to train these models. We examined the feasibility, tolerability, patient characteristics, and data quality of a novel protocol for internet-based treatment research in psychiatry that may help advance this field. Methods: A fully internet-based protocol was used to gather repeated observational data from patient cohorts receiving internet-based cognitive behavioural therapy (iCBT) (N = 600) or antidepressant medication treatment (N = 110). At baseline, participants provided > 600 data points of self-report data, spanning socio-demographics, lifestyle, physical health, clinical and other psychological variables and completed 4 cognitive tests. They were followed weekly and completed another detailed clinical and cognitive assessment at week 4. In this paper, we describe our study design, the demographic and clinical characteristics of participants, their treatment adherence, study retention and compliance, the quality of the data gathered, and qualitative feedback from patients on study design and implementation. Results: Participant retention was 92% at week 3 and 84% for the final assessment. The relatively short study duration of 4 weeks was sufficient to reveal early treatment effects; there were significant reductions in 11 transdiagnostic psychiatric symptoms assessed, with the largest improvement seen for depression. Most participants (66%) reported being distracted at some point during the study, 11% failed 1 or more attention checks and 3% consumed an intoxicating substance. Data quality was nonetheless high, with near perfect 4-week test retest reliability for self-reported height (ICC = 0.97). Conclusions: An internet-based methodology can be used efficiently to gather large amounts of detailed patient data during iCBT and antidepressant treatment. Recruitment was rapid, retention was relatively high and data quality was good. This paper provides a template methodology for future internet-based treatment studies, showing that such an approach facilitates data collection at a scale required for machine learning and other data-intensive methods that hope to deliver algorithmic tools that can aid clinical decision-making in psychiatry. [ABSTRACT FROM AUTHOR]

Purpose: Post-stroke depression (PSD) occurs in one-third of stroke survivors, leading to a substantial decrease in quality of life as well as delayed functional and neurological recovery. Early detection of patients at risk and initiation of tailored preventive measures may reduce the medical and socioeconomic burden associated with PSD. We sought to review the current evidence on pharmacological and non-pharmacological prevention of PSD. Materials and Methods: We conducted a systematic review using PubMed/MEDLINE and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled studies. Eligible studies were included when performed within 1 year after the index cerebrovascular event. Animal and basic research studies, studies lacking a control group, review papers, and case reports were excluded. Results: Out of 150 studies screened, 37 met our criteria. Among the strategies identified, administration of antidepressants displayed the most robust evidence for preventing PSD, whereas non-pharmacological interventions such as psychotherapy appear to be the most frequently used approaches to prevent depression after stroke. Research suggests that the efficacy of PSD prevention increases with the duration of preventive treatment. Seven out of 11 studies (63%) that used pharmacological and eight out of 16 (50%) that used non-pharmacological interventions reported a positive preventive effect on PSD. Conclusion: Overall, the current literature on PSD prevention shows heterogeneity, substantiating a need for well-designed randomized controlled trials to test the safety and efficacy of pharmacological as well as non-pharmacological and composite prevention regimens to minimize the risk of PSD in stroke survivors. Integrative strategies combining personalized non-pharmacological interventions such as educational, mental, and physical health support, and pharmacological strategies such as SSRIs may be the most promising approach to prevent PSD. [ABSTRACT FROM AUTHOR]

The United States Food and Drug Administration issued a Black Box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo. Subsequently, some researchers have concluded that the Black Box warning caused severe unintended consequences; specifically, they have argued that the warning led to reduced use of antidepressants among youth, which led to more suicides. In this paper, we critically examine research regarding the Black Box warning's alleged deleterious consequences. One study claimed that controlled trials did not actually find an increased risk of suicidality among youth taking fluoxetine relative to those taking placebo, but its measure of suicidality is likely invalid. We found that ecological time series studies claiming that decreasing antidepressant prescriptions are linked to higher rates of suicide attempts or actual suicides among youth were methodologically weak. These studies exhibited shortcomings including: selective use of time points, use of only a short-term time series, lack of performing statistical analysis, not examining level of severity/impairment among participants, inability to control confounding variables, and/or use of questionable measures of suicide attempts. Further, while some time-series studies claim that increased antidepressant prescriptions are related to fewer youth suicides, more recent data suggests that increasing antidepressant prescriptions are related to more youth suicide attempts and more completed suicides among American children and adolescents. We also note that case-control studies show increased risk of suicide attempts and suicide among youth taking antidepressants, even after controlling for some relevant confounds. As clinical trials have the greatest ability to control relevant confounds, it is important to remember such trials demonstrated increased risk of suicidality adverse events among youth taking antidepressants. The Black Box warning is firmly rooted in solid data whereas attempts to claim the warning has caused harm are based on quite weak evidence. [ABSTRACT FROM AUTHOR]

QT prolongation is one of the main unwanted cardiac effects caused by drugs, such as anti-psychotics and anti-depressants, inducing mainly via hERG channel dysfunction. The precise and underlying mechanism of adverse effects on hERG channel are still indecisive, but these effects limit their use in patients with cardiac risk factors. The aim of this review was studying mechanism of Long-term QT syndrome induction via hERG channel dysfunction by these Drugs. Search was performed in PubMed, and Scopus. All human, animals, and cell lines studies, English and full text publications were included. Among 1280 papers, 23 studies were eligible for more assessments. Quality of studies cheeked by two researchers independently. most of studies were done on anti-psychotic drugs, especially typical class. Most used investigated method to long-term QT induction was patch clamp. results suggests in susceptible cases with heart risk factors, these drugs should be taken with caution and monitored. • Addressing one of the underling mechanisms of hERG channel dysfunction related to long-term QT syndrome. • Determining that hERG channel dysfunction is the main mechanism in inducing LQTS of anti-psychotic and anti-depressant drugs. • Suggesting that these drugs should be taken with caution and monitoring in susceptible cases with heart risk factors. [ABSTRACT FROM AUTHOR]

Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense, Spatholobus suberectus, etc. Studies have proved that formononetin has good anti-inflammatory, antitumor, antioxidant, antidepressant, anxiolytic and other pharmaco- logical effects. This paper summarizes the pharmacological action and molecular mechanism of formononetin, in order to provide a theoretical basis for the development and clinical application of formononetin. [ABSTRACT FROM AUTHOR]

Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75–1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians' awareness in antidepressant prescription should optimize their potential while reducing this risk. [ABSTRACT FROM AUTHOR]

Abstract The domain of psychiatric drug development is currently witnessing a notable transformation, with a paramount emphasis on targeting nonmonoamine receptors and exploring inventive mechanisms of action. This paper presents an overview of the ongoing advancements in antipsychotic and antidepressant drug development. Historically, antipsychotics predominantly targeted dopamine receptors, but there is now an escalating interest in drugs that act on alternative receptors, exemplified by the TAAR1 receptor. One noteworthy candidate is Ulotaront (SEP‐363856), an agent acting as a TAAR1 agonist with 5‐HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side‐effects. Similarly, MIN‐101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)‐approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor‐positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK‐653 (NBI‐1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric modulation, respectively. This paper underscores the transformative potential of these novel drug candidates in psychiatric treatment and their ability to address cases that were previously treatment‐resistant. By focusing on nonmonoamine receptors and introducing innovative mechanisms, these drugs offer a promising prospect of improved outcomes for individuals suffering from schizophrenia and MDD. Thus, sustained attention and dedication to the development of such drugs are essential to augmenting the therapeutic options available for psychiatric patients.

Backgrounds: Bipolar depression is still a very difficult to treat condition with low success rates of antidepressant drugs, high rates of morbidity and suicide risk and antidepressant-emergent mania risk. Despite a growing body of evidence has been generated over the last decade about Light Therapy (LT) as an effective treatment for depression the management of it continues to be a point of debate for Bipolar Disorder especially when considering non-seasonal pattern.Methods: We systematically screened current literature using the PubMed electronic platform. We considered "mood disorder", "depression" and "light therapy" as keywords for the search.Results: We retrieved 1907 papers. After the screening, we selected 11 papers to be included in the analysis, treating 195 patients affected by bipolar depression. 5 studies were RCT studies. The overall analysis, including non-RCTs, showed a positive effect of the treatment in all the included studies (ESs: -1.46, 95% CI:-1.677 to -1.242; p<0.001). A significant effect of LT compared to placebo was found also in RCTs (ESs: -0.501, 95% CI: - 0.777 to -0.225; p<0.001).Limitations: A high heterogeneity between the studies was found when including non-RCTs and the number of RCTs was small CONCLUSION: We confirmed the -efficacy of LT as antidepressant non-pharmacological therapy also in bipolar depression. [ABSTRACT FROM AUTHOR]

Compared with placebo + antidepressants, esketamine + antidepressants significantly improved remission in patients with treatment-resistant depression (RR = 1.39, 95% CI 1.18 to 1.63, P < 0.0001) (Figure 5). All of them were conducted in the last 3 years, the treatment phase of the patients was a double-blind induction treatment period, and the patients were all treated with conventional antidepressants combined with esketamine or placebo. Efficacy and safety of fixed doses of intranasal esketamine as an add-on therapy to oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study. Compared with the control group, esketamine + antidepressant significantly improved the response to antidepressants in patients with treatment-resistant depression (RR = 1.28, 95% CI 1.12 to 1.46, P = 0.0002) (Figure 4). [Extracted from the article]

This paper presents a novel, high sensitive analytical method for electrochemical determination of viloxazine at boron-doped diamond electrode using differential pulse voltammetry (DPV). The verification of viloxazine electrochemical behavior proved that viloxazine undergoes diffusion controlled, one-electron irreversible oxidation process. Optimization stage allowed for selection of acetate buffer solution (pH 5; 0.1 mol dm−3) as the best suitable supporting electrolyte and determination of DPV parameters. The calibration curve was obtained in the concentration range 0.1–20.0 µmol dm−3 with the detection limit equal to 0.04 µmol dm−3, respectively. The optimized procedure was validated by studying the sensitivity, accuracy, and precision of obtained results. The proposed method was successfully employed for viloxazine determination in spiked tap and river water samples with recovery of 95.8–98.8%. [ABSTRACT FROM AUTHOR]

The second-generation antidepressants (SGAs) are used widely in patients with Alzheimer's disease (AD) for the treatment of mood disorder, sleep disturbance and psychiatric symptoms. Several evidences from AD mice confirmed that antidepressants could delaying cognitive decline. However, the conclusions varied in randomized controlled trials (RCTs) based on patients. This meta-analysis summarizes the cognitive impact of SGAs on AD patients with different neuropsychiatric symptoms (NPS). Results show there is no effect on cognition and depression between SGAs treatment and controls, and this remains in subgroups analyses of duration of medication (<12 weeks or ≥12 weeks), drug classes (SSRIs or non-SSRIs), combination with anti-dementia medication, various NPS, and degree of AD. The available evidence provides no support for the efficacy of SGAs for cognition and depression of AD patients. The implications of the findings and their mechanism relevance are also discussed in this paper. [ABSTRACT FROM AUTHOR]

Xeromphis. uliginosa (Retz.) is an extinctive Bangladeshi medicinal plant that is locally used for the treatments of pain, diabetes, diarrhea, depressant, and other diseases. The present study was conducted to evaluate the peripheral analgesic activity (PAA), central analgesic activity (CAA), central nervous system antidepressant activity (CNS-AD), antidiarrheal activity (ADA), and hypoglycaemic activity (HGA) of methanolic root extract of X. uliginosa (MREXU) in a mice model. The acetic acid-induced writhing inhibition and tail flick method were applied to determine the PAA and CAA of MREXU. The CNS-AD was measured using the phenobarbitone sodium-mediated sleeping method whereas, the castor oil-induced antidiarrheal method was used to determine the ADA of the crude extracts. To determine the HGA of MREXU crude extract, the tail tipping technique was conducted in a mice model. The MREXU displayed potential PAA and CAA in mice models. The MREXU 200 and 400 mg/kg significantly inhibit the number of writings along with diclofenac sodium. On the other hand, MREXU both doses significantly inhibit thermal stimulus after 60 and 90 minutes respectively. In the CNS-AD study, crude extract of 200 and 400 mg/kg significantly increase the onset of sleep by decreasing the duration of sleep. Similarly, the dose of 200 mg/kg significantly reduced diarrheal faeces for the whole 4 hours of experiments. The heartiest outcome of MREXU was displayed in the HGA assay. Both doses of MREXU significantly reduced the blood sugar level for the entire 3 hours of the experiments. In this study, it is revealed that the root of MREXU has extremely significant blood sugar-reducing activity, potential CNSAD and mild to moderate nociceptive activity in the mice model. [ABSTRACT FROM AUTHOR]

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/βCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/βCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/βCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1β, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/βCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/βCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1β levels. The effects of the NEO/βCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress. [ABSTRACT FROM AUTHOR]

Aim: To determine the efficacy and safety of pharmacogenomics (PGx)-guided antidepressant prescribing in patients with depression through an umbrella review and updated meta-analysis. Methods: A comprehensive systematic search was conducted on PsycINFO, PubMed, Embase and the Cochrane databases. The pooled effect sizes of randomized controlled trials (RCTs) were expressed as mean differences for continuous data and risk ratios for noncontinuous data. Results: Patients who received PGx-guided medications were 41% to 78% more likely to achieve remission and 20% to 49% more likely to respond to antidepressants than patients receiving treatment-as-usual (TAU). Conclusion: PGx-guided antidepressant prescribing improves the treatment of depression. However, the significance and magnitude of the benefit varies widely between studies and different PGx testing panels. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to measure sequential rates of obesity, gestational diabetes, polycystic ovary syndrome, and anxiety, depression, and antidepressant treatment in pregnant women in Australia between 2008 and 2022. Materials and Methods: BMI ≥ 30 (obesity), BMI ≥ 35 (severe obesity/obesity class II and III), gestational diabetes, Type II diabetes, polycystic ovary syndrome, clinical diagnoses of anxiety and depression, antidepressant treatment. Results: Women taking antidepressants in pregnancy were substantially more vulnerable to obesity (BMI ≥ 30) with rates of 43.59% vs 26.00%. Women taking antidepressants in pregnancy also had higher rates of severe obesity (BMI ≥ 35) at 25.63% vs 12.98%. A small minority of these women were also nearly 6 times more likely to drink alcohol in pregnancy (2.7% vs 0.47%) and to use other drugs in pregnancy such as amphetamines (0.35% vs 0.07%) and cannabis (3.4% vs 0.73%). When compared with peers matched for diagnoses of depression and anxiety, women taking antidepressants were still more likely to be obese (25.63% vs 20.17%) though this difference was not so marked. Rates of obesity have increased in the cohort studied from 26.86% to 31.27%; of gestational diabetes from 3.98% to 21.77%; of polycystic ovary syndrome from 1.47% to 5.47%; of anxiety from 1.11% to 5.77%; of depression from 2.17% to 4.31%, and antidepressant treatment from 1.45% to 2.16%. Conclusions: Obesity, gestational diabetes and polycystic ovary syndrome rates have substantially increased between 2008 and 2022 in Australia. Rates of anxiety in pregnant women have increased substantially over this period, as have rates of depression. Women living with depression and anxiety in pregnancy are increasing to suffer obesity and related metabolic conditions. Antidepressant treatment may also increase these women's vulnerability to obesity and severe obesity. [ABSTRACT FROM AUTHOR]

One of the most important developments in psychopharmacology in the past decade has been the emergence of novel treatments for mood disorders, such as psilocybin for treatment-resistant depression. Psilocybin is most commonly found in different species of mushroom; however, the literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just psilocybin-containing mushrooms, and includes both psychedelic and non-psychedelic species. In the current review, we systematically review the preclinical literature on mushroom and fungus extracts, and their effects of animal models of depression and tests of antidepressant activity. The PICO structure, PRISMA checklist and the Cochrane Handbook for systematic reviews of intervention were used to guide the search strategy. A scoping search was conducted in electronic databases PubMed, CINAHL, Embase and Web of Science. The literature search identified 50 relevant and suitable published studies. These included 19 different species of mushrooms, as well as seven different species of other fungi. Nearly all studies reported antidepressant-like effects of treatment with extracts. Treatments were most commonly delivered orally, in both acute and chronically administered studies to predominantly male rodents. Multiple animal models of depression were used, the most common being unpredictable chronic mild stress, while the tail suspension test and forced swim test were most frequently used as standalone antidepressant screens. Details on each experiment with mushroom and fungus species are discussed in detail, while an evaluation is provided of the strengths and weaknesses of these studies. [ABSTRACT FROM AUTHOR]

Depressive and anxiety disorders constitute some of the most prevalent mental disorders around the world. For years, the development of new lead compounds for drug discovery in this field has been an area of great attention. Recently, a series of tetrahydrocarbazole derivatives have demonstrated important anxiolytic-like activity, associated with their structures and stereochemistry. Here, we present a study of the antidepressant effect and anxiolytic-like activity of a fused thiopyrano-piperidone-tetrahydrocarboline (compound 4). The antidepressant and anxiolytic-like effects of 4 (1–50 mg/kg p.o.) were assessed with the tail suspension test and the hole-board test, respectively. This study determined the possible mechanisms involved in the anxiolytic-like actions of 4 using inhibitors or neurotransmission and evaluated its interaction with 5HT2A receptors using a molecular docking study. As an analog to the tetrahydrocarbazole core, the tetrahydrocarboline derivative showed anxiolytic-like activity (ED50 = 13 mg/kg p.o.) in the hole-board test, with a comparable effect to the reference drug, 1.5 mg/kg clonazepam, with the possible participation of the serotonergic system. [ABSTRACT FROM AUTHOR]

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Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant and anxiolytic applications. Benzylpiperazine is the prototype of piperazine derivatives; this substance is the main component of recreational drugs, partly due to its stimulant and euphoric effects. This paper describes some piperazine derivatives used therapeutically as antipsychotic (clozapine), antidepressant (vortioxetine) and anxiolytic (buspirone) drugs. [ABSTRACT FROM AUTHOR]

In this paper, we have reported the synthesis and biological evaluation of nineteen (S)-N-substituted-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives as novel candidate antidepressant and anticonvulsant agents. Compounds 2h, 2k, 2r, and 2s exhibited better potent antidepressant activity and displayed the antidepressant effects in a dose-dependent manner from 10 to 30 mg/kg in the FST and TST. And, we found that the best antidepressant effect of compounds 2r and 2s are likely mediated by an increase in central nervous system 5-HT and NE. In addition, compounds 2r and 2s also exhibited the anticonvulsant activity against MES-induced seizures. Thus, compounds 2r and 2s may be a useful antidepressant adjunct therapy for treating depression in patients with epilepsy. In addition, compounds 2r and 2s showed the anti-inflammatory activity and the excellent analgesic activity. Several scholars have postulated the anti-inflammatory and analgesic effects of antidepressant drugs, suggesting that they may be possess a similar mechanism of action. [ABSTRACT FROM AUTHOR]

Background: Depression is common, particularly among women of childbearing age, and can have far-reaching negative consequences if untreated. Efficacious treatments are available, but little is known about how women make depression treatment decisions during pregnancy. The purpose of this narrative review is to interpretively synthesize literature on women's decision making (DM) regarding antidepressant use during pregnancy.Methods: The databases PubMed, CINAHL, and PsycINFO were searched between May 2015 and August 2017 for peer-reviewed, English-language papers using terms such as "depression," "pregnancy," and "DM." The literature matrix abstraction method was used to systematically abstract data from full articles that met criteria for inclusion.Results: Of the articles abstracted (N = 10), half did not cite a DM theory on which the work was based. Key aspects of DM for this population were need for information and decision support, desire for active participation in DM, reflection on beliefs and values, evaluation of treatment option sequelae, and societal expectations. Treatment DM for depression during pregnancy is particularly impacted by the stigma associated with depression and societal expectations of pregnant women related to medication use during pregnancy. These findings, however, were based on studies of predominantly Caucasian and well-educated women.Conclusions: Women require a nonjudgmental environment, in which shared DM feels safe, to foster positive DM experiences and outcomes. Future research is needed to define how to best support women to make depression treatment decisions in pregnancy, with particular attention to DM in the second and third trimesters of pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) approved for treatment of fibromyalgia in Australia, but is used for depression in Europe and elsewhere. This paper will briefly review milnacipran and its utility in psychiatry for the treatment of depression.Conclusion: Milnacipran is a dual reuptake inhibitor of noradrenaline and serotonin, with greater effect on noradrenaline than serotonin, in contrast to the related drugs venlafaxine, desvenlafaxine and duloxetine. Rapidly absorbed irrespective of food, milnacipran has a half-life of approximately 8 hours, reaches steady state in 2 days and is excreted renally. Milnacipran helps a minority of patients with fibromyalgia by reducing pain and fatigue. It is also an effective antidepressant with efficacy comparable to venlafaxine and duloxetine, and a side effect profile characteristic of SNRIs. The dose range is 50-200 mg, in divided doses. Milnacipran may be useful for patients with depression and pain, and endogenous depression characterised by anergia, psychomotor retardation and hypersomnia. Caution is necessary in the presence of heart disease, hypertension, renal impairment, epilepsy, glaucoma, bipolar disorder, and bleeding tendency. Milnacipran is likely to be a useful late antidepressant option in treatment-resistant patients, as well as those with chronic pain, anergia and hypersomnia. [ABSTRACT FROM AUTHOR]

Objective This paper is a systematic review on seizures under treatment with substances licensed for major depression. Method Systematic review protocol is available in PROSPERO registration number CRD42016034010. Twenty-five substances were selected according to frequencies of prescriptions and publications. A PubMed search was conducted with "substance name" and "seizure." Results A total of 2291 articles were screened, out of which 164 fulfilled inclusion criteria. Data synthesis was possible only to a limited extent due to heterogeneity of included patients, observation periods, methods, and outcomes. Evidence for an at most moderate, but still low, risk ( > 0.1 % under regular doses) was found highest for clomipramine, followed by quetiapine, amitriptyline, venlafaxine, citalopram, sertraline, trazodone, mirtazapine, paroxetine, bupropion, and escitalopram. For fluoxetine and duloxetine, the risk seems to be negligible. For the other, mostly newer, substances, sufficient evidence was not available. An increased risk for lithium, as reported in many reviews and textbooks, could not be confirmed. Conclusions Antidepressive treatment is rather safe in terms of risk of seizures and also can be generally recommended in the treatment of patients with epilepsy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to clarify the inconsistent findings in the association between antidepressant use and the risk of epithelial ovarian cancer (EOC). Methods: This study is a meta‐analysis of observational studies retrieved from the PubMed, EMBASE, and Web of Science databases prior to August 15, 2017. Two researchers independently screened studies and extracted study characteristics and risk estimates. The odds ratios (OR) and 95% confidence intervals (CI) of EOC risk were summarized using an inverse variance weighted random‐effects model. Heterogeneity between studies was assessed with the I2 statistic. Results: Eight case–control studies involving 7878 EOC cases and 73 913 controls were identified. Compared with non‐use, use of antidepressants was not significantly associated with EOC risk (summarized OR = 1.10, 95% CI: 0.91–1.32, I2 = 74.4%). Similar null results were also observed in the use of selective serotonin reuptake inhibitors (OR = 1.04, 95% CI = 0.80–1.35), tricyclic antidepressants (OR = 1.01, 95% CI = 0.79–1.30), and other antidepressant drugs (OR = 0.91, 95% CI = 0.74–1.12). Subgroup analyses of study characteristics, stratified by the type of control subjects, geographic location, exposure assessment, number of cases, and adjustment for potential confounders, showed that the ORs were broadly consistent across strata. The OR per 1 year‐increment of duration was 0.99 (95% CI = 0.94–1.05, I2 = 40.0%, P = 0.154). Additionally, the OR for the greatest intensity of antidepressant use compared with never use was 0.82 (95% CI = 0.70–0.98, I2 = 0%, P = 0.489). Furthermore, no evidence of publication bias was detected through Funnel plots as well as Egger's and Begg's tests. Conclusions: There is no association between antidepressant use and EOC risk. Further prospective studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brainmetabolismand receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies. [ABSTRACT FROM AUTHOR]

Background: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. Aims: To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. Methods: We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. Results: We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). Conclusions: Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus. [ABSTRACT FROM AUTHOR]

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16 h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES. Summary points Desvenlafaxine (DES) is a hydrophilic drug showing initial burst release from conventional dosage forms. It is rapidly absorbed after its oral administration, which intensifies its side effects. Its burst release was overcome by incorporating it into Compritol-based solid lipid nanoparticles (SLNs). DES-SLNs prepared by the hot-melt encapsulation technique had a particle size of 156 nm with an encapsulation efficiency of 69.50% and appeared spherical with a smooth surface when observed under a scanning electron microscope. The DES-SLNs had a polydispersity index value of 0.139, indicative of homogenous dispersion. x-ray diffraction analysis revealed the conversion of DES from crystalline form to amorphous form, exhibiting molecular dispersion of the DES in the Compritol matrix. An in vitro release study of DES presented a sustained release of drug from lipid matrix with no initial burst release that is observed in commercially available tablets of DES. [ABSTRACT FROM AUTHOR]

Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research. Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients. Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as "Chaihu Shugan" and "depression" to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines. Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brainderived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs. [ABSTRACT FROM AUTHOR]

Prenatal depression affects approximately 10% to 15% of women. Guidelines recommend supporting women to make informed treatment decisions; however, minimal evidence exists regarding this decision-making process. This study aimed to develop a constructivist grounded theory of prenatal antidepressant treatment decision-making. Semi-structured interviews were conducted with purposively sampled women from the community or specialty clinics (N = 31). Iterative data collection and analysis, theoretical sampling, and member checking supported model sufficiency. In the Creating Comfort in Choice theory that we developed, participants were highly conscious of societal stigma toward mental illness and prenatal medication use, so fear, anxiety, and guilt dominated decision-making. Participants navigated dynamically among three clusters of decision-making activities: seeking information, making sense of information, and self-soothing. "Seeking information" included internal and external processes. In "making sense of information," participants appraised available evidence. In "self-soothing," participants engaged in coping strategies to try to alleviate painful emotions. The Creating Comfort in Choice theory can support patient-oriented decision-making regarding prenatal mental healthcare. [ABSTRACT FROM AUTHOR]