Serotonin Reuptake Inhibitors Research Articles

Pharmacotherapy and electroconvulsive therapy prescription for women with depressive and anxiety disorders in a psychiatric mother-baby unit.

The purpose of this study was to understand the pharmacotherapy and electroconvulsive therapy (ECT) prescription of women with depression and anxiety admitted to an Australian inpatient psychiatric mother-baby unit (MBU) and compare prescription to national clinical practice guidelines. A retrospective audit was conducted on women diagnosed with depression or anxiety admitted to a public psychiatric inpatient MBU from March 2017 to July 2019. Data was captured at three time points to assess demographic, clinical and pharmacotherapy treatment characteristics. Descriptive statistics were completed. Of the 74 women, 57 women had depression, with 73% prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) and 14% provided ECT during admission. For women with anxiety (n = 17), 23% were prescribed a benzodiazepine with concurrent antidepressant prescription. SSRI prescription increased, with other antidepressant prescription up trending through admission. Atypical antipsychotic prescription was increased initially and trended downwards at discharge. This study explored the therapeutic armamentarium employed for the treatment of mothers admitted to an inpatient psychiatric MBU with depression and anxiety. The results point to the intricate prescribing practices in a naturalistic setting and highlight that prescribing practices were in line with national guidelines.

Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis.

Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.

Rapid reorganization of serotonin projections and antidepressant response to 5-HT1A-biased agonist NLX-101 in fluoxetine-resistant cF1ko mice

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) like fluoxetine remain a first-line treatment for major depression, but are effective in less than half of patients and can take 4–8 weeks to show results. In this study, we examined cF1ko mice with genetically induced upregulation of 5-HT1A autoreceptors that reduces 5-HT neuronal activity. These mice display anxiety- and depression-related behaviors that did not respond to chronic fluoxetine treatment. We examined treatment with NLX-101, a biased agonist that preferentially targets 5-HT1A heteroreceptors. By testing different doses of NLX-101, we found that a dose of 0.2 mg/kg was effective in reducing depression-related behavior in cF1ko mice without causing hypothermia, a 5-HT1A autoreceptor-mediated response. After 1 h, this dose activated dorsal raphe 5-HT neurons and cells in the medial prefrontal cortex (mPFC), increasing nuclear c-fos labelling in cF1ko mice. In cF1ko mice but not wild-type littermates, 0.2 mg/kg NLX-101 administered 1 h prior to each behavioral test for two weeks reduced depressive behavior in the forced swim test, but increased anxiety-related behaviors in the open field, elevated plus maze, and novelty suppressed feeding tests. During this treatment, NLX-101 induced widespread increases in the density of 5-HT axons, varicosities, and especially synaptic and triadic structures, particularly in depression-related brain regions including mPFC, hippocampal CA1 and CA2/3, amygdala and nucleus accumbens of cF1ko mice. Overall, NLX-101 was rapid and effective in reducing depressive behavior in SSRI-resistant mice, but also induced anxiety-related behaviors. The increase in serotonin innervation induced by intermittent NLX-101 may contribute to its behavioral actions.

Peripheral Serotonin Controls Dietary Fat Absorption and Chylomicron Secretion via 5-HT4 Receptor in Males.

Postprandial dyslipidemia is commonly present in people with type 2 diabetes and obesity and is characterized by overproduction of apolipoprotein B48-containing chylomicron particles from the intestine. Peripheral serotonin is emerging as a regulator of energy homeostasis with profound implications for obesity; however, its role in dietary fat absorption and chylomicron production is unknown. Chylomicron production was assessed in Syrian golden hamsters by administering an olive oil gavage and IP poloxamer to inhibit lipoprotein clearance. Administration of serotonin or selective serotonin reuptake inhibitor, fluoxetine, increased postprandial plasma triglyceride (TG) and TG-rich lipoproteins. Conversely, inhibiting serotonin synthesis pharmacologically by p-chlorophenylalanine (PCPA) led to a reduction in both the size and number of TG-rich lipoprotein particles, resulting in lower plasma TG and apolipoprotein B48 levels. The effects of PCPA occurred independently of gastric emptying and vagal afferent signaling. Inhibiting serotonin synthesis by PCPA led to increased TG within the intestinal lumen and elevated levels of TG and cholesterol in the stool when exposed to a high-fat/high-cholesterol diet. These findings imply compromised fat absorption, as evidenced by reduced lipase activity in the duodenum and lower levels of serum bile acids, which are indicative of intestinal bile acids. During the postprandial state, mRNA levels for serotonin receptors (5-HTRs) were upregulated in the proximal intestine. Administration of cisapride, a 5-HT4 receptor agonist, alleviated reductions in postprandial lipemia caused by serotonin synthesis inhibition, indicating that serotonin controls dietary fat absorption and chylomicron secretion via 5-HT4 receptor.

Pharmacological Treatments for Gambling Disorder: A Current Review of Literature

This narrative review aims to examine pharmacological treatment modalities for gambling disorder (GD) by analyzing recent literature and identifying significant trends in the field. A thorough examination of relevant literature, focusing primarily on recent studies and reviews, in order to identify significant pharmacological treatment approaches and current trends. Results: The review identifies several pharmacological approaches for GD, including opioid antagonists, serotonergic agents, dopaminergic modulators, glutamatergic agents, and mood stabilizers. Recent studies suggest that opioid antagonists such as naltrexone and nalmefene show promise in reducing gambling urges and behaviors. Additionally, serotonergic agents like selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in alleviating the impulsivity and compulsivity associated with GD. Dopaminergic and glutamatergic agents, while showing some potential, require further investigation for their role in GD treatment. Mood stabilizers, particularly lithium, appear to be beneficial, especially in individuals with co-occurring bipolar affective disorder. Pharmacological interventions play a crucial role in the management of GD, with opioid antagonists and SSRIs emerging as promising options. However, further research is needed to elucidate the optimal pharmacotherapeutic approach and develop more targeted treatments for GD. Integration of pharmacotherapy with psychotherapeutic interventions may enhance treatment outcomes for individuals with GD.

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling

Misexpression of the E3 ubiquitin ligase gene UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, additional genomic copies of UBE3A give rise to the autism, muscle hypotonia and spontaneous seizures characteristics of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown that glial-driven expression of the UBE3A ortholog dube3a led to a “bang-sensitive” phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-driven dube3a expression on motor coordination and seizure susceptibility in Drosophila.To quantify seizure-related behavioral events, we developed and trained a hidden Markov model that identified these events based on automated video tracking of fly locomotion. Both glial and neuronal driven dube3a expression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous seizure-associated immobilization events, that were clearly observed at high-temperature (38 °C). Using a tethered fly preparation amenable to electrophysiological monitoring of seizure activity, we found glial-driven dube3a flies display aberrant spontaneous spike discharges which are bilaterally synchronized. Neither neuronal-dube3a overexpressing flies, nor control flies displayed these firing patterns. We previously performed a drug screen for FDA approved compounds that can suppress bang-sensitivity in glial-driven dube3a expressing flies and identified certain 5-HT modulators as strong seizure suppressors. Here we found glial-driven dube3a flies fed the serotonin reuptake inhibitor vortioxetine and the 5-HT2A antagonist ketanserin displayed reduced immobilization and spike bursting, consistent with the previous study. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

IMPACT OF PROLONGED USE OF ANTIDEPRESSANTS ON NEUROPLASTICITY

Antidepressants are widely used in the treatment of depressive and anxiety disorders and are essential for the management of these conditions. However, the impact of prolonged use of these drugs on neuroplasticity - the brain’s ability to reorganize itself, forming new neural connections - has been a topic of growing interest and debate in the scientific community. This abstract addresses the effects of prolonged use of antidepressants on neuroplasticity, considering their implications for long-term mental health. The aim of this paper is to examine and synthesize the scientific evidence on the impact of long-term use of antidepressants on neuroplasticity, with a focus on how these changes can influence the effectiveness of treatment and the long-term prognosis of patients. This study conducts a literature review on the long-term effects of antidepressants on neuroplasticity, investigating both the therapeutic potentials and the associated risks. The review focuses on how neuroplasticity can influence treatment outcomes, tolerance to antidepressants, and the impacts on specific populations, such as the elderly and individuals with hormonal variations. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), have been shown to influence neuroplasticity in several ways. Pre-clinical and clinical studies suggest that prolonged use of these drugs can promote neurogenesis, particularly in the hippocampus, an area of the brain crucial for memory and learning. This neurogenic effect is associated with an improvement in depressive symptoms and the brain’s ability to adapt to new challenges. In addition, antidepressants appear to increase the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), which plays a vital role in the survival and growth of neurons. The increase in BDNF levels may contribute to the restoration of synaptic connectivity, which is often compromised in patients with depression. However, there is controversy about the long-term effects of continuous use of these drugs on neuroplasticity. Some studies suggest that, despite the initial benefits, prolonged use can lead to a “rigidity” in brain plasticity, making it difficult to adapt to new treatments or therapeutic strategies. In addition, the impact on other areas of the brain, such as the prefrontal cortex, which is involved in decision-making and emotional control, is still poorly understood and requires further research. These findings raise questions about the optimal duration of treatment with antidepressants and the need for continuous monitoring of patients’ long-term mental health. Neuroplasticity may be a crucial factor in individual response to treatment and the possibility of relapse or development of resistance to treatment. Therefore, the prolonged use of antidepressants has a significant impact on neuroplasticity, initially promoting neurogenic effects and an increase in synaptic connectivity, which can improve depressive symptoms. However, the long-term effects still need to be better understood, especially with regard to the possible “rigidity” in brain plasticity and the implications for ongoing treatment. To maximize the benefits and minimize the risks, it is essential that treatment with antidepressants is carefully monitored, with attention to changes in neuroplasticity over time. More research is needed to elucidate the underlying mechanisms and guide clinical practice towards more effective and safer strategies for the management of depression and other related disorders.

Preoperative SSRI use increases perioperative transfusion need in patients undergoing surgical procedures on the hip joint.

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for psychiatric conditions. Previous studies have shown that SSRIs can increase bleeding risk by affecting platelet aggregation. However, their impact on perioperative outcomes in hip surgery remains uncertain. This case-control study examines the link between preoperative SSRI use and perioperative transfusion requirements in hip surgery patients. Data from the M161Ortho dataset of Pearl Diver patient records database were utilized. Patients who underwent hip joint surgery between 2010 and 2022 and had documented preoperative SSRI use within one month prior to surgery were included. Patients with coagulopathy disorders or coagulopathy medication use were excluded. Perioperative transfusion need was defined as receiving red blood cell or whole blood transfusions on the same date or within 10 days following the surgery. A total of 75,374 patients with preoperative SSRI use were matched with an equal number of non-SSRI users. Preoperative SSRI use was associated with an increased risk of requiring perioperative transfusion (5.7% vs. 5.1%, P < 0.001). Subgroup analysis demonstrated increased transfusion risk in patients undergoing pinning (2.6% vs. 1.8%, P = 0.02), open reduction with internal fixation (ORIF) (8.9% vs. 8.2%, P = 0.007), and total hip arthroplasty (THA) (3.8% vs. 3.4%, P < 0.001), but no significant difference was observed in patients undergoing hemiarthroplasty. Clinicians should be aware of the potential risk of increased perioperative transfusion requirements in hip surgery patients using SSRIs, especially during pinning, ORIF, and THA procedures. It is essential to consider this when managing patients on SSRIs before hip surgery.

Efficacy of antidepressants in functional dyspepsia: Systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults. Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE)approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0. Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]),respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04]). Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population.

Increased Odds of Cognitive Impairment in Adults with Depressive Symptoms and Antidepressant Use.

The relationship between antidepressant use and class with cognition in depression is unclear. This study aimed to evaluate the association of cognition with depressive symptoms and antidepressant use (class, duration, number). Data from the National Health and Nutrition Examination Survey were examined for cognitive function through various tests and memory issues through the Medical Conditions questionnaire. Depressive symptoms were assessed using the Patient Health Questionnaire-9. A total of 2867 participants were included. Participants with depressive symptoms had significantly higher odds of cognitive impairment (CI) on the animal fluency test (aOR=1.89, 95% CI=1.30, 2.73, P=0.002) and Digit Symbol Substitution test (aOR=2.58, 95% CI=1.34, 4.9, P=0.007), as well as subjective memory issues (aOR=7.25, 95% CI=4.26, 12.32, P<0.001) than those without depression. There were no statistically significant associations between any of the CI categories and depressive symptoms treated with an antidepressant and antidepressant use duration. Participants who were using more than one antidepressant had significantly higher odds of subjective memory issues than those who were using one antidepressant. Specifically, users of atypical antidepressants, selective serotonin reuptake inhibitors, or tricyclic antidepressants (TCAs) had significantly higher odds of subjective memory issues in comparison to no antidepressants, with TCAs showing the largest odds (aOR=4.21, 95% CI=1.19, 14.86, P=0.028). This study highlights the relationship between depressive symptoms, antidepressant use, and CI. Future studies should further evaluate the mechanism underlying this phenomenon.

Exploring the Antibiofilm Effect of Sertraline in Synergy with Cinnamomum verum Essential Oil to Counteract Candida Species.

The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming ineffective against them. In recent decades, there has been a notable increase in systemic fungal infections, primarily caused by Candida species, which are progressively developing resistance to azoles. Moreover, Candida species biofilms are among the most common in clinical settings. In particular, they adhere to biomedical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. In recent years, many research programs have concentrated on the development of novel compounds with possible antimicrobial effects to address this issue, and new sources, such as plant-derived antimicrobial compounds, have been thoroughly investigated. Essential oils (EOs), among their numerous pharmacological properties, exhibit antifungal, antibacterial, and antiviral activities and have been examined at a global scale as the possible origin of novel antimicrobial compounds. A recent work carried out by our research group concerned the synergistic antibacterial activities of commercially available and chemically characterized Cinnamomum verum L. essential oil (C. verum EO) in association with sertraline, a selective serotonin reuptake inhibitor whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. The aim of this work was to explore the synergistic effects of C. verum EO with sertraline on both planktonic and sessile Candida species cells. Susceptibility testing and testing of the synergism of sertraline and C. verum EO against planktonic and sessile cells were performed using a broth microdilution assay and checkerboard methods. A synergistic effect was evident in both the planktonic cells and mature biofilms, with significant reductions in fungal viability. Indeed, the fractional inhibitory concentration index (FICI) was lower than 0.5 for all the associations, thus indicating significant synergism of the associations with the Candida strains examined. Moreover, the concentrations of sertraline able to inhibit Candida spp. strain growth and biofilm formation significantly decreased when it was used in combination with C. verum EO for all the strains considered, with a reduction percentage in the amount of each associated component ranging from 87.5% to 97%.

Persistent postural perceptual dizziness (PPPD) in pediatric patients after COVID-19 infection

BackgroundPatients with long-COVID suffer from symptoms that continue or develop after a COVID-19 or SARS-CoV-2 infection and are present for four or more weeks after the initial infection. This case series describes a group of previously healthy adolescent patients with long-COVID who were seen in a pediatric vestibular clinic for evaluation of severe dizziness and were diagnosed with persistent postural-perceptual dizziness (PPPD). By presenting their symptoms, management and treatment effects, this study aims to provide a diagnostic and therapeutic framework for providers who encounter these patients. MethodsPatient records were reviewed for past medical history, symptoms, physical exam findings, results of audiometric and vestibular testing, dizziness handicap inventory for patient caregiver (DHI-pc) scores, and treatment recommendations. Parents of patients were contacted for a follow up survey to assess treatment adherence and outcomes including changes in symptoms and return to activity. ResultsA series of 9 adolescent patients were referred from a multidisciplinary long-COVID clinic and diagnosed with PPPD. Recommended treatment included vestibular physical therapy, selective serotonin reuptake inhibitor medication, and cognitive behavioral therapy. The majority of patients experienced an improvement in their symptoms, and all patients had improved activity levels and DHI-pc scores after treatment. ConclusionTo the best of our knowledge, no previous reports exist discussing PPPD in long-COVID patients. This case series provides insight into symptom evolution and treatment efficacy in this patient population.

The Effect of Antidepressants on Withdrawal in Patients with Alcohol Dependence: A Retrospective Study.

The use of electronic health records has expanded in the past decades, with healthcare entities storing terabytes of patient health data. In this study, we investigated how these databases can be utilized to generate clinically relevant information. We used the Office of Addiction Services and Supports Client Data Systems data merged with the NYS Medicaid Data Warehouse to study the relationship of certain antidepressants on alcohol withdrawal (AW) rates in patients with alcohol dependence (AD). We found that in patients with AD, bupropion was associated with a significantly reduced rate of AW compared to selective serotonin reuptake inhibitors (SSRIs). This may be due to the ability of bupropion to inhibit dopaminergic reuptake. This retrospective study provides the advantage of being faster and less expensive than randomized controlled trials (RCTs).

Pharmacological interventions for pruritus in adult palliative care patients.

Pharmacological interventions for pruritus in adult palliative care patients.

Dangerous Intersection of Alcoholism and Othello Syndrome: A Comprehensive Review of Delusional Jealousy and Treatment Strategies.

The modern pace of life, increased susceptibility to stressors, and easy access to psychoactive substances have contributed to the increase in the number of people addicted to alcohol. Alcoholism has serious and life-threatening consequences, one of which is brain damage causing morbid jealousy, otherwise known as Othello syndrome. The disease, currently classified as a subtype of delusional disorder, manifests itself in groundless and dangerous judgments about a partner's sexual infidelity. People with Othello syndrome constantly believe in their partner's infidelity despite inadequate evidence of it. Patients become aggressive toward their partners as well as themselves, which is why in a fit of anger they can commit murder or suicide. Othello syndrome can occur as a symptom of an underlying mental illness, but it is most often associated with brain damage caused by chronic alcohol use. Antipsychotic drugs and serotonin reuptake inhibitors are used in pharmacotherapy. Targeted treatment using the neuropeptide oxytocin, which modulates the transmitter systems responsible for disease symptoms, is also being considered. The use of oxytocin seems groundbreaking, but it remains at the research stage. The treatment of addictions and primary diseases, as well as long-term cognitive-analytic psychotherapy, also have a huge impact. Othello syndrome is a life-threatening disease with an insidious course and serious consequences. This article aims to review the manifestations of morbid jealousy, including delusional disorder, and the association with alcoholism.

Transcriptome networks and physiology related to cardiac function and motor activity are perturbed in larval zebrafish (Danio rerio) following exposure to the antidepressant citalopram

Citalopram is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and is often detected in aquatic environments. Here, we measured the acute toxicity of citalopram at environmentally relevant concentrations to zebrafish embryos/larvae and utilized RNA-seq to reveal potential mechanisms of toxicity. We also assessed behavioral outcomes in larval zebrafish. Zebrafish embryos were exposed continuously to embryo rearing medium (ERM), or one concentration of 0.1, 1, 10, 100, and 1000 μg/L citalopram for 7 days post-fertilization (dpf). No acute toxicity was noted for citalopram over 7-days in developing zebrafish, nor were there any effects on hatch rates; however, exposure resulted in a dose-dependent decrease in heart rate at 2 dpf. Reactive oxygen species were also increased in 7-day old larvae zebrafish exposed to 100 μg/L citalopram. There were 29 genes differentially expressed in fish exposed to 10 μg/L citalopram [FDR <0.05] and 79 genes differentially expressed in fish exposed to 1000 μg/L citalopram [FDR <0.05]. In the 1000 μg/L citalopram treatment, there were several transcripts downregulated related to muscle function, including myhz2, myhz1, and myom1. Twenty-five gene set pathways were shared between exposure concentrations including ‘IL6 Expression Targets’, ‘Thyroid Stimulating Hormone (TSH) Resistance in Congenital Hypothyroidism’, and ‘GFs/TNF - > Ion Channels.' Enrichment of KEGG pathways revealed that 1000 μg/L citalopram altered processes related to the proteosome and cardiac muscle contractions. Larval zebrafish at 7 dpf showed hypoactivity with exposure to ≥10 μg/L citalopram. This may be related to the downregulation of transcripts involved in muscle function. Overall, our results show that citalopram as a pharmaceutical pollutant may have an adverse influence on aquatic species' ability to survive by reducing their abilities to elude predators (e.g. cardiac output, locomotor activity). This study improves mechanistic understanding of the potential harm citalopram may cause fish and contributes to environmental risk assessments for SSRIs in aquatic species.

Prefrontal cortex-nucleus reuniens-hippocampus network exhibits sex-differentiated responses to stress and antidepressant treatment in rats.

Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression. In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine. Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity. RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females. Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.

Adsorption of Nefazodone on single-wall carbon nanotube as an antidepressant drug delivery: A DFT study

Nefazodone, a derivative of triazolones, belongs to a group of heterocyclic aromatic compounds. It is used as an antidepressant for treating depression, including major depressive disorder. Unlike other antidepressant groups such as selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors, Nefazodone does not share chemical similarities. Recent research has focused on studying the reactivity and chemical structure influenced by Nefazodone's medicinal features in the drug's adsorption process on single-wall Carbon Nanotube (CNT) as an adsorbent in the gas phase using density functional theory (DFT), Becke, 3-parameter, Lee–Yang–Parr (B3LYP) 6-311+G(d,p) basis set (DFT/B3LYP/6-311+G(d,p)). The effect of electronegative atoms and phenyl groups on the adsorption of Nefazodone on CNT has been studied by calculating the adsorption energy for all active sites. On the other hand, thermodynamic values, such as Gibbs free energy (−4873.09 kJ), Enthalpy (−4872.83 kJ), and Entropy (903.09 J/mol.kelvin), as well as thermodynamic capacity (497.45 J/mol.kelvin), were calculated to show the reactivity of Nefazodone. The stability and reactivity were examined through the energies of the highest occupied molecular orbital (HOMO) (−5.53 eV) and lowest unoccupied molecular orbital (LUMO) (−0.58 eV) of Nefazodone, highlighting ten regions with chemical activity, all of which are thermodynamically stable. Some Electronic parameters such as chemical potential (µ), electronegativity (χ), softness (σ), hardness (η), and electrophilicity index (ω) were calculated. The comparison of chemical potential values between Nefazodone(−3.05 eV) and the more stable complex (−3.81 eV) illustrates the more reactivity for the complex. This suggests that Nefazodone can be transferred to biological systems through such an adsorption mechanism.

Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response

This study compared the power of the novel inflammatory markers systemic immune inflammation index (SII) and the system inflammation response index (SIRI) versus the classical hematological indices neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and platelet counts in distinguishing between major depressive disorder (MDD) with and without suicide attempts and distinguishing the non-response to selective serotonin reuptake inhibitor (SSRI) treatment. A total of 139 young adult MDD patients and 54 healthy controls (HC) were included. We found that, in comparison to HC, baseline NLR, PLR, SII, and SIRI were significantly higher in MDD patients, but only NLR and SII had area under the ROC curve (AUC) values greater than 0.7. MDD patients with suicide attempts (SA) showed significantly higher baseline MLR and SIRI, and a tendency to increase NLR compared to those without SA. In terms of AUC, sensitivity, and specificity, NLR was better than MLR, SIRI, SII, and PLR in distinguishing SA. Non-responders to SSRI treatment showed a significant increase in baseline platelet count and PLR compared to responders with an AUC greater than 0.7. These findings highlight the potential benefit of combining novel and classical hematological indices in predicting depression, suicide attempts and treatment response.