Antidepressant Medicine Research Articles

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

From Perspective of Hippocampal Plasticity: Function of Antidepressant Chinese Medicine Xiaoyaosan.

The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.

The role of TrkB signaling-mediated synaptic plasticity in the antidepressant properties of catalpol, the main active compound of Rehmannia glutinosa Libosch.

Ethnopharmacological relevanceRehmannia glutinosa Libosch. (RGL) is a famous ethnic medicine contained in antidepressant Chinese medicine formulas and is traditionally clinically used for depression. We have recently confirmed that RGL enhanced synaptic plasticity in a mouse model of Chinese medical syndrome and that catalpol may be the representatively pharmacological component responsible for its improvement in synaptic plasticity and treatment of depression. Impaired synaptic plasticity is closely linked to major depression. Tyrosine kinase receptor B (TrkB) signaling has recently been discovered as a key pathway for synaptic plasticity improvement and antidepressant discovery. However, to date, it is unknown whether the target of catalpol to improve synaptic plasticity involves TrkB and whether its antidepressant mechanism involves synaptic plasticity mediated by TrkB signaling. Aim of studyThis study aims to elucidate the potential antidepressant target and mechanisms of catalpol, the main active compound of RGL, through TrkB signaling-mediated synaptic plasticity. Materials and methodsWe have recently predicted through molecular networking strategy (including network pharmacology, molecular docking, and molecular dynamics simulation) that catalpol may exert its antidepressant effects by regulating TrkB signaling and thus modulating essential synaptic plasticity proteins. Then, this study used classic behavioral tests, targeted diagnostic reagents, Nissl and Golgi staining, immunohistochemical analysis, immunofluorescence analysis, Western blot, enzyme-linked immunosorbent assay, and Real-time PCR to confirm the potential target and signaling of catalpol to improve synaptic plasticity for the treatment of depression. ResultsThe data showed that catalpol could improve synaptic plasticity and depressive behaviors, and its action pathway was predicted to involve TrkB signaling. Subsequently, the blockade of TrkB abolished the improvement of synaptic plasticity by catalpol and its antidepressant properties, which validated that TrkB signaling was the key pathway for catalpol to improve synaptic plasticity and exert antidepressant properties. Inhibition of COX-2 was likely to be a necessary facilitator for the antidepressant efficacy of catalpol via the TrkB target and TrkB-mediated synaptic plasticity. ConclusionTrkB signaling-mediated synaptic plasticity plays a key role in the antidepressant properties of catalpol. This study provides critical information for the development of new and targeted antidepressant therapies or treatment strategies by catalpol. However, considering the existence of sex differences in depression (female depression is 2–3 times than that of males) and not exploring the antidepressant sex specificity of catalpol is a limitation, we will investigate the sex specificity of the antidepressant effects and molecular mechanisms of catalpol on sex-specific animals in the future to provide a preclinical basis for more accurate and targeted medication of catalpol.

Evaluation of the on–off fluorescence method for facile measurement of vilazodone in pharmaceutical dosage form; Application to content uniformity testing and greenness evaluation

Vilazodone is a recently approved antidepressant medicine used for treating major depressive disorder. A simple, extremely sensitive, accurate and green spectrofluorimetric method was constructed for its determination through formation of ion-pair complex with erythrosine B. The formation of ion-pair complex lowers the dye’s native fluorescence emission measured at 552 nm (λ ex = 530 nm). In terms of analysis, the system’s parameters for producing the vilazodone-erythrosine B complex have been optimized. The reaction was carried out in Teorell-Stenhagen buffering solution (pH 4.6). The fluorescence emission intensity of the dye decreased linearly in the range of 20 – 600 ng mL−1 and the correlation coefficient was 0.9999. The quantitation and detection limit values were 18.5 and 6.1 ng mL−1, respectively. The proposed strategy has been validated according to the ICH criteria. The proposed technique was thoroughly employed for evaluating vilazodone in raw material and pharmaceutical tablet dosage form. Furthermore, it was also successfully used for content uniformity testing. Lastly, using four advanced tools namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach (AGREE), the greenness of the established technique was evaluated.

ACE I/D polymorphism in cognitive impairment and depression among North Indian adults: a pilot study

BackgroundCognitive impairment and depression are two common mental health conditions affecting millions worldwide. CI and depression both have complex etiology and multiple genetic and environmental factors are thought to play a role in their onset and progression. Further, CI and depression often occur as comorbidities, indicating an overlap in their etiologies. The likelihood of developing major depressive illness and CI, the prognosis in response to treatments, and the possibility of adverse reactions to antidepressant medicines are all significantly influenced by genetics. Looking at the limited literature on the role of ACE I/D polymorphism in CI and depression among Indian populations, the present population-based pilot study was conducted with the aim to understand the association of ACE I/D polymorphism with CI and depression among North Indian adults.ResultsThe present study was conducted among 195 individuals aged 30 years and above. The results of the present study show that the distributions of some of the studied sociodemographic variables, viz., gender, educational status, and employment status, were significantly different between those with and without CI, where a higher percentage of females, nonliterate and unemployed participants were in CI group than in the without CI group (p value < 0.05). For cognitive impairment, none of the models showed a statistically significant association with ACE I/D genotypes or alleles. For depression, two of the models showed a statistically significant association with ACE I/D genotypes or alleles. The ID + DD (D allele) and DD genotypes of ACE I/D polymorphism, with II as a reference, were found to pose a significantly reduced risk for depression (p value < 0.05).ConclusionIn conclusion, the findings of this study suggest that the D allele of ACE I/D gene polymorphism poses a potentially reduced risk of depression among North Indian adults. In the case of cognitive impairment, the findings suggest that gender, educational status, and employment status may be important factors to consider when assessing the risk of cognitive impairment. However, more research is needed to better understand the complex interplay between sociodemographic and genetic factors and cognitive impairment and depression.

The anti-depression effect and potential mechanism of the petroleum ether fraction of CDB: Integrated network pharmacology and metabolomics

The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.

Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

Green synthesis of copper(II) oxide nanoparticles covered on multiwalled carbon nanotubes modified screen-printed electrode as rapid electrochemical sensing platform for detection of doxepin

In the current research, a modified screen-printed electrode has been made by depositing a copper(II) oxide nanoparticle upon the surface of multiwalled carbon nanotubes (CuO/MWCNTs). Through the use of X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), and mapping, the characterization of the CuO/MWCNTs modifier was examined. The XRD analysis confirms the in-situ formation of copper(II) oxide nanoparticles with MWCNT. FESEM studies reveal the simultaneous existence of nanoparticles and nanotubes in the prepared nanocomposite material. This kind of morphological orientation has significantly improved the nanocomposite’s catalytic properties. Moreover, EDS analysis and elemental mapping depicts that the presence of nanocomposite containing the elements of Cu, O, and C mentioned. Examining the modified electrode's electrochemical activity revealed good stability and conductivity under a diffusion-controlled procedure, making it an ideal working electrode. Additionally, the doxepin oxidation process at the modified electrode’s surface, an antidepressant medicine, has been examined. The modified electrode had a high doxepin sensitivity at an applied voltage of 780 mV. With a detection limit of 0.17 nM (signal/noise = 3), linear range was also obtained over a wide concentration range of 0.001 µM to 400.0 µM (R2 = 0.9998). What's more, the modified electrode is very resistant to ion poisoning and efficiently prevents interference from the oxidation of typicalinterfering species. Moreover, the CuO/MWCNTs electrode has been utilized to measure the doxepin concentration in actual samples. Aside from having an improved electrocatalytic capability, the modified electrode also has a low working potential and good stability, as well as high sensitivity.

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review.

Depression is one of the most mutilating conditions in the world today. It has been difficult to make advancements toward better, more effective therapies since the introduction of antidepressant medicines in the late 1950s. One important field of medicinal chemistry is the synthesis of antidepressant molecules through metal-catalyzed procedures. The important role that different transition metals, including iron, nickel, ruthenium, and others, serve as catalysts in the synthesis of antidepressants is examined in this review. Key structural motifs included in antidepressant drugs such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and others can be synthesized in a variety of effective ways using metal-catalyzed steps. This review examines current developments in the catalytic synthesis of antidepressants and their potential application over the previous thirteen years.

Opioid analgesics for nociceptive cancer pain: Acomprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Vertically well-aligned ZnO nanorods based biosensor for determination of paeoniflorin as an antidepressant medicine

In the study, a novel method for detecting paeoniflorin (PF), a significant antidepressant drug, is described that makes use of vertically aligned zinc oxide nanorods (ZnO NRs). Vertically aligned zinc oxide (ZnO) nanorods and rGO were electrodeposited on the GCE electrode surface, according to structural investigations performed using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). According to electrochemical experiments, ZnO NRs and rGO increase the electron transfer rate and support catalytic activity, making it easier to detect and quantify PF in the electrochemical sensor. The results exhibited that the linear range and sensitivity of ZnO-rGO/GCE were, respectively, 0.1–1305 μg/mL and 0.03792 μA/μg.mL−1. The PF sensor also achieved a low detection limit of 3.4 ng/mL. It was investigated to see how well a PF sensor worked to analyze a sample of human serum. Relative standard deviations (RSD) for sample detections for the proposed PF sensor were all below 4.13 %, according to analytical analyses utilizing the conventional addition approach, with recoveries ranging from 96.00 % to 99.25 %. These findings affirm that the proposed PF sensor exhibits a high degree of accuracy, rendering it well-suited for clinical applications and the analysis of human bodily fluids.

Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats.

Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population. Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems. Male and female rats were gavaged with FLX (5mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment. Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals. Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.

Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons

Major depressive disorder (MDD) is a serious disease and a burden to patients, families and society. Rodent experiments and human studies suggest that several neuropeptide systems are involved in mood regulation. The aim of this study is two-fold: (i) to monitor, with qPCR, transcript levels of the substance P/tachykinin (TAC), NPY and CCK systems in bulk samples from control and suicide subjects, targeting five postmortem brain regions including locus coeruleus (LC); and (ii) to analyse expression of neuropeptide family transcripts in LC neurons of ‘normal’ postmortem brains by using laser capture microdissection with Smart-Seq2 RNA sequencing. qPCR revealed distinct regional expression patterns in male and female controls with higher levels for the TAC system in the dorsal raphe nucleus and LC, versus higher transcripts levels of the NPY and CCK systems in prefrontal cortex. In suicide patients, TAC, TAC receptors and a few NPY family transcript levels were increased mainly in prefrontal cortex and LC. The second study on ‘normal’ noradrenergic LC neurons revealed expression of transcripts for GAL, NPY, TAC1, CCK, and TACR1 and many other peptides (e.g. Cerebellin4 and CARTPT) and receptors (e.g. Adcyap1R1 and GPR173). These data and our previous results on suicide brains indicates that the tachykinin and galanin systems may be valid targets for developing antidepressant medicines. Moreover, the perturbation of neuropeptide systems in MDD patients, and the detection of further neuropeptide and receptor transcripts in LC, shed new light on signalling in noradrenergic LC neurons and on mechanisms possibly associated with mood disorders.

Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3β and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3β and FoxO3a were upregulated. Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

Ketamine Improves the Glymphatic Pathway by Reducing the Pyroptosis of Hippocampal Astrocytes in the Chronic Unpredictable Mild Stress Model.

Ketamine as a glutamate receptor antagonist has a rapid, potent, and long-lasting antidepressant effect, but its specific mechanism is still not fully understood. Depression is associated with elevated levels of glutamate and astrocyte loss in the brain; the exploration of the relationships between ketamine's antidepressant effect and astrocytes has drawn great attention. Astrocytes and aquaporin 4 (AQP4) are essential components of the glymphatic system, which is a brain-wide perivascular pathway to help transport nutrients to the parenchyma and remove metabolic wastes. In this study, we investigated pyroptosis-associated protein Nlrp3/Caspase-1/Gsdmd-N expression in the hippocampus of mice and the toxic effect of high levels of glutamate on primary astrocytes. On this basis, the protective mechanism of ketamine is explored. A single administration of ketamine (10 mg/kg) remarkably relieved anxious and depressive behaviors in the sucrose preference test, elevated plus maze test, and forced swim test. Meanwhile, ketamine reduced the level of hippocampus Nlrp3 and the expression of its downstream molecules in chronic unpredictable mild stress (CUMS) mice model by western blot and reduced the colocalization of Gfap and Gsdmd by nearly 25% via immunofluorescent staining. Ketamine also increased the Gfap-positive cells and AQP4 expression in the hippocampus of the CUMS mice. More important, ketamine increased the distribution of the fluorescent tracer of CUMS mice. Treatment with 128 mM glutamate in cortical and hippocampus astrocytes increased the level of Nlrp3, and Gsdmd-N, and ketamine alleviated high glutamate-induced pyroptosis-associated proteins. In summary, these results suggest that high glutamate-induced astrocyte pyroptosis through the Nlrp3/Caspase-1/Gsdmd-N pathway which was inhibited by ketamineandketamine can improve the damaged glymphatic function of the CUMS mice. The present study indicates that inhibiting astrocyte pyroptosis and promoting the glymphatic circulation function are a new mechanism of ketamine's antidepressant effect, and astrocyte pyroptosis may be a new target for other antidepressant medicines.

Systematic Analysis of the Mechanism of Polygoni Multiflori Caulis in Improving Depressive Disorder in Mice via Network Pharmacology Combined with Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Exactive Orbitrap Mass Spectrometer.

Depressive disorder (DD) is a common chronic and highly disabling disease. Polygoni Multiflori Caulis (PMC), a traditional Chinese medicine, has been listed in the 2020 edition of the Chinese Pharmacopoeia. Here, the antidepressant effects and mechanisms of PMC were explored for the first time. We observed the safety of PMC at a 10-fold clinically equivalent dose. Depressed mice were induced by chronic unpredictable mild stress (CUMS) and were used to evaluate the antidepressant effects of PMC via the sucrose preference test and the tail suspension test. The composition of PMC was identified by ultra-high performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer, and the active components, important targets, and potential mechanism of PMC in DD treatment were predicted via network pharmacology. Investigation included active compounds and DD-related targets screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, PMC-compound-target-pathway- DD network construction, and Molecular docking. In the safety evaluation of PMC, no toxic side effects or deaths occurred. There were no significant differences in liver function (ALT, AST, and TP; P > 0.05) and kidney function (BUN, CRE, and UA; P > 0.05) in each group of mice. Compared to the control group, the model group of mice showed significantly decreased sucrose preference and significantly increased immobility time (P < 0.01 or P < 0.05). Compared with the model group, the mice in the PMC low, medium, and high dose groups showed a significant decrease in immobility time and a significant increase in sucrose preference. In the PMC-Compound-Target-Pathway-DD network, 54 active compounds, 83 common targets, and 13 major signaling pathways were identified for the treatment of DD. Molecular docking verified that the active compounds could effectively bind with the hub targets. PMC is a relatively safe antidepressant herbal medicine with its potential mechanism involving multiple compounds, targets, and pathways.

Profil peresepan dan analisis risiko racikan antidepresan di sebuah apotek di Yogyakarta

In Yogyakarta, the number of patients suffering from depression reached 5.5%. To enhance the therapeutic benefit, psychiatrists frequently prescribe a combination of antidepressants to their patients. To identify the risk for incompatibility, the prescription profile of antidepressant medicines that are compounded together must be examined. The purpose of this study is to examine the prescribing patterns of compounded medications designated as antidepressants in a Yogyakarta pharmacy. The prescription is the research subject in this descriptive exploratory study. Prescriptions that satisfied the inclusion criteria were gathered, and the frequency of prescriptions was calculated. Two medications with the greatest prescribing frequency were then examined for potential interactions and incompatibility. Folic acid is the most commonly prescribed medicine when combined with another. It was formerly used with sertraline HCl, maprotiline HCl, trifluoperazine HCl, and diazepam. The psychiatrist was used to mixing three to four active drugs administered in capsules. The drug combination has various interactions that must be properly monitored. These findings can be used by the doctor to choose the best medicine combination.

A CASE REPORT ON AYURVEDIC MANAGEMENT OF TRIGEMINAL NEURALGIA WITH RESPECT TO ANANTHAVATA

Trigeminal neuralgia is a distinctive facial pain syndrome characterized by severe electric shock-like pain in one or more branches of the trigeminal nerve. It is also known as tic douloureux as it is often accompanied by facial spasms or tic. The treatment includes anticonvulsants, antidepressant medicines, and other surgical measures. According to Ayurvedic classics it can be considered as Ananthavata. Ananthavata is a Sannipathika siroroga. The main treatment principles are Siravyadha and Vatapittahara measures. The primary objective of this paper is to discuss the action of Ayurvedic management in trigeminal neuralgia with the support of a clinical case. Ayurvedic treatments can significantly reduce the severity and recurrence of symptoms.

The impact of a reimbursement rate reduction on the utilization of antiulcer, antidepressants and antidiabetics in Portugal: A time series analysis

ABSTRACT Background According to international research, an increase in the patient share of pharmaceutical expenditure results in a decrease in medicines utilization. In 2010, the Portuguese government reduced the reimbursement rate for certain therapeutic classes. The aim of this study was to evaluate the impact of raising cost to the patient on the utilization of medicines. Methods Between January 1996 and December 2015, medicines utilization and cost to the patient per DDD of antihypertensive, antidyslipidemic, antidiabetic, antiulcer and antidepressant medicines were compared. A segmented linear regression of two time series – before and after the change in reimbursement percentage – was used. Results During the two time series, there was an increase in the utilization of antidepressants and antiulcer medicines. The consumption growth decelerated following the reduction in reimbursement rate. Cost to the patient decreased for both classes across the two time series, although the trend accelerated during the second. Conclusion These findings suggest that a decrease in the reimbursement rate had little impact on the utilization of medicines. It is reasonable to assume that the reduction in percentage covered by the Portuguese National Health System was gradually compensated by the decrease in the absolute amount that patients paid for medicines.