Search

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.

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]

Summary The discovery of rapid eye movement sleep in 1953 led to numerous studies investigating the relationship between rapid eye movement sleep abnormalities and psychiatric disorders. The most salient findings were the association of rapid eye movement sleep alterations—reduced rapid eye movement sleep latency, increased rapid eye movement sleep volume of total sleep, and increased rapid eye movement density—with major depression. This paper briefly reviews the history of rapid eye movement sleep research in psychiatry with a focus on the work related to major depressive disorder and some of the various theories that have been proposed to explain the associated rapid eye movement sleep abnormalities. Given the increasing evidence that rapid eye movement sleep is important for emotional processing, memory and cognition, a better understanding of the underlying mechanisms for the relationship between rapid eye movement sleep and mood disorders could lead to improved treatments for these common and disabling illnesses. [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]

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.

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]

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]

Recent guidelines suggest that the overall quantity and duration of antidepressant prescriptions should be reduced. In this paper, we comment on the evidence both for and against this view.We critically review the arguments proposed by proponents of antidepressant deprescribing in the context of the evidence-base for the treatment of depression.Proponents of deprescribing do not address the substantive issues of whether inappropriate prescribing has been demonstrated, and when prescribing is needed. Their arguments for deprescribing are rebutted in this context.Whether or not to deprescribe antidepressant medication needs to take into consideration the risk-benefit profile of the decision, the responsibility for which needs to be shared and based on the context of the patient’s depression, their preferences, experiences and perspectives. [ABSTRACT FROM AUTHOR]

Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm2 vs. CRS, 173/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1β signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment. [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]

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as "rabbit" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0–4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive–compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology. [ABSTRACT FROM AUTHOR]

Antidepressants, including duloxetine, are a significant cause of drug-induced hyponatremia, which can disrupt the continuation of medication. Tolvaptan is beneficial for correcting hyponatremia caused by the syndrome of inappropriate antidiuresis, but its impact on duloxetine-induced hyponatremia remains unknown. We used male Sprague-Dawley rats to examine the impact of duloxetine treatment on lithium-induced nephrogenic diabetes insipidus (Li-NDI) and to evaluate whether the results were reversed by co-treatment with tolvaptan. To induce Li-NDI, lithium chloride (40 mmol lithium/kg dry food) was administered for 2 weeks. Duloxetine (50 mg/kg/day) and tolvaptan (10 mg/kg/day) were also administered in food to assess their individual effects over the same period. At the end of each animal experiment, kidneys were harvested to measure levels of cAMP, vasopressin-2 receptor (V2R), cAMP-responsive element binding protein 1 (CREB-1), aquaporin-2 (AQP2), and prostaglandin E2 (PGE2). Water diuresis was induced in the Li-NDI rats, and duloxetine treatment reduced polyuria while increasing urine osmolality. Duloxetine treatment prevented the decrease in total AQP2, AQP2 phosphorylation at serine 256, and CREB-1 phosphorylation in Li-NDI rats. The V2R mRNA level was also reduced in Li-NDI rats and restored by duloxetine treatment. In the subsequent experiment, the decreased water diuresis in Li-NDI rats treated with duloxetine was reversed by co-treatment with tolvaptan. Tolvaptan co-treatment also reversed the changes in AQP2 protein and CREB-1 phosphorylation in the renal cortex and medulla. The decreased cAMP levels in Li-NDI rat kidneys were elevated by duloxetine treatment, and this elevation was reversed by co-treatment with tolvaptan. However, the elevated PGE2 levels in Li-NDI rat kidneys were not affected by either duloxetine alone or tolvaptan co-treatment. In conclusion, antidiuresis was induced by duloxetine in Li-NDI and reversed by tolvaptan co-treatment through alterations in the V2R-cAMP-AQP2 pathway. These findings could underlie the mechanism of duloxetine-induced hyponatremia and suggest the potential usefulness of tolvaptan in treating drug-induced hyponatremia. [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]

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]

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]

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: 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]