The present study aimed to investigate the characteristics of abnormal resting-state brain-network connectivity and the reorganization effects of antidepressant drug escitalopram oxalate treatment in patients with major depressive disorder (MDD), and to explore spatial correlations between brain network alterations and gene expression profiles. We employed a longitudinal study design to recruit 113 patients with MDD and 114 healthy controls (HCs) between November 2020 and October 2022. Clinical symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired using a Siemens 3.0 T MRI scanner. At baseline, patients with MDD exhibited significantly reduced functional connectivity (FC) within the default mode network (DMN) compared to HCs, along with significantly increased FC between the sensorimotor network (SMN) and both the frontoparietal network (FPN) and the salience network (SN) (False Discovery Rate, FDR-corrected, p < 0.05). Following treatment with escitalopram oxalate, MDD patients showed a significant enhancement in intra-DMN connectivity, as well as a significant reduction in SMN-FPN and SMN-SN connectivity (FDR-corrected, p < 0.05). Notably, the degree of increase in intra-DMN connectivity was significantly and negatively correlated with improvement in core depressive symptoms (r = - 0.305, p = 0.026), while the reduction in SMN-DMN connectivity was positively correlated with the alleviation of somatic symptoms (r = 0.362, p = 0.008). Further neuroimaging-guided transcriptomics analysis indicated that these alterations in brain network connectivity were linked to biological pathways, such as the Wnt signaling. In conclusion, our findings demonstrate a multidimensional imbalance in brain network connectivity in MDD and show that antidepressant treatment can partially ameliorate aberrant connectivity patterns. These neural changes are closely associated with symptomatic improvements, offering valuable imaging-based evidence for understanding the neurobiological mechanisms of MDD and informing the development of personalized treatment strategies.

Introduction: Escitalopram oxalate (ESC) was extensively reported to improve insomnia in patients with depression/anxiety. The serotonin transporter gene (SLC6A4) was involved in regulating insomnia. However, it is still unclear whether ESC improves insomnia by regulating SLC6A4 expression. Therefore, this study aimed to investigate whether ESC improves insomnia by regulating SLC6A4 based on clinical and animal experiments. Methods: The clinical and animal experiments were involved in this study. For clinical experiments, after all 110 participants were divided into four groups, the portable sleep electroencephalogram monitor, HAMA14 scale, and HAMD24 scale were used to evaluate patients’ sleep quality, anxiety, and depression. For animal experiments, after all 18 ICR male mice were randomly divided into three groups (n = 6), the sodium pentobarbital-induced sleeping test, locomotor activity test, elevated plus maze, and open field test were used to evaluate mice’s sleep quality and anxiety- and depression-like behaviors. The H&E staining was used to determine pathological injuries in mice’s hippocampal tissues. The ELISA kits were adopted to detect the 5-HT, norepinephrine (NE), gamma-aminobutyric acid (GABA), and glutamate (Glu) levels in the hypothalamus tissue and the corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the serum. The PubChem, DrugBank, and Therapeutic Target Database were employed to predict the potential targets of ESC. The immunohistochemical staining and Western blot were applied to assay the SLC6A4, 5-HTR1A, and 5-HTR2A expression levels in the hippocampal tissues of mice. Results: ESC shortened the sleep latency, extended the sleep time, enhanced the sleep efficiency, and improved anxiety and depression in patients and mice. ESC mitigated the pathological injuries in mice’s hippocampal tissues. ESC effectively regulated mice’s neurotransmitter levels and hypothalamic-pituitary-adrenal (HPA) axis homeostasis, including upregulating 5-HT and GABA and downregulating NE, Glu, CRH, ACTH, and CORT. Moreover, SLC6A4 was predicted as the potential target of ESC. ESC prominently inhibited SLC6A4 expression (p < 0.001) and regulated 5-HTR1A and 5-HTR2A expression (p < 0.001) in hippocampal tissues. Conclusion: Taken together, ESC was suitable for treating insomnia in the clinic and improved insomnia by targeting SLC6A4 to regulate the HPA axis in mice.

ObjectiveThis study aimed to establish a UPLC-MS/MS method for the simultaneous quantification of five antidepressants: venlafaxine (VEN) and its metabolite O-desmethylvenlafaxine (ODV), mirtazapine (MIR), sertraline (SER), escitalopram (ESC), and vortioxetine (VTX) in human plasma and saliva. By analyzing real-world therapeutic drug monitoring (TDM) data, this study aimed to identify key factors influencing drug concentrations thereby optimizing personalized treatment strategies for patients with depression and advancing precision medicine.MethodsFollowing liquid-liquid extraction for plasma and protein precipitation for saliva, analyte concentrations were determined using a fully validated UPLC-MS/MS method. Validation included assessments of selectivity, linearity, accuracy, precision, extraction recovery, matrix effects, stability, and dilution integrity. The established method was applied to clinical samples, with further investigation into how clinical factors, including age, BMI, renal function (as measured by GFR), total protein (TP), albumin levels, and concomitant medications, influenced the concentration-to-dose ratio (CDR).ResultsThe method demonstrated excellent linearity (5–500 ng/mL) with all validation parameters meeting acceptance criteria. The established method was successfully applied to analyze 566 plasma and 39 saliva samples. TDM revealed significant variations in target attainment rates among different antidepressants, along with varying degrees of dose-concentration correlations. Multivariate analysis demonstrated that the CDR of VEN + ODV was primarily influenced by age and GFR, while the CDR of MIR showed a significant association with BMI. The CDR of SER was affected by both BMI and TP levels. The CDR of ESC was modulated by age, concomitant medications, and renal function.ConclusionThis study demonstrated that TDM-based individualized medication strategies can support the optimization of antidepressant efficacy. Saliva monitoring requires further validation. Clinicians should adopt dynamic, patient-specific monitoring to enhance precision medicine outcomes in depression management.

Formulation and Evaluation of Escitalopram Oxalate Oral Films by 32 Factorial Design

Drugs are challenging to remove from water due to their chemical stability, low biodegradability, and resistance to conventional water treatments. Thus, this work aimed to synthesize a niobium-based nanozeolite (Nb-nFAU) to remove the Escitalopram Oxalate drug (EsOx) from water, in continuous operation. Nb-nFAU was obtained by hydrothermal method, combining zeolite precursors and ammonium niobium(V) oxalate (10 wt.%). The Nb-nFAU was characterized by XRD, FEG–SEM with EDX, N2 porosimetry, DLS, and pHZCP. XRD identified faujasite, niobium pentoxide, and lueshite for Nb-nFAU. Moreover, S BET = 234.8 ± 1.9 m2 g−1, V p = 0.121 ± 0.01 cm3 g−1, D p = 13.7 ± 2.6 nm, ZP = −19.7 ± 2.5 mV, PDI = 0.67 ± 0.07, and pHZCP 7.06 were reported for Nb-nFAU. The experimental data were fitted by Clark, Thomas, and Yoon–Nelson models, which indicated high affinity between EsOx and Nb-nFAU. Nb-nFAU showed higher bed adsorption capacity (q bed = 8.79 mg g−1) than pristine nanozeolite, nFAU (q bed = 6.37 mg g−1), and higher breakthrough time (53.11 min versus 34.77 min). nFAU and Nb-nFAU showed q max = 82.5 and 92.4 mg g−1, respectively. Therefore, the incorporation of Nb proved to enhance the adsorption capacity of nanozeolites, being useful as a starting point for scale-up studies.

PK/PD modeling of the effect of Escitalopram combined with Docetaxel in the treatment of breast cancer with depression in mice.

Integrative therapy with moxibustion and repetitive transcranial magnetic stimulation enhances outcomes in patients with post-stroke depression.

Escitalopram oxalate is a widely used drug for treating depressive conditions in various age groups. However, it exerts systemic side effects beyond its primary action in the brain, including impacts on bone, with negative repercussions on bone quality. Yet, the influence of this drug on fracture healing has not been investigated, and this is the focus of the present study. Fractures were created in the right femur diaphysis in healthy adult rats and those with osteopenia induced by prior ovariectomy. All animals underwent right femur fracture, and the subsequent healing process was examined. Four groups were established: Healthy Adult Sham, Osteoporosis Sham, Healthy Adult Escitalopram, and Osteoporosis Escitalopram. Oral administration of escitalopram was conducted daily via gavage for 35 days, while sham treatment consisted of distilled water administration via gavage. The bone callus analysis included the determination of bone mineral density, Computed microtomography images, mechanical resistance testing, and histomorphometry. Exposure to escitalopram resulted in the disruption of the bone callus, characterized by a decrease in trabecular thickness, an increase in trabecular separation, and greater deposition of type I collagen. Bone mineral density and strength, however, remained unaffected. In conclusion, escitalopram oxalate negatively interfered with fracture repair in both healthy and osteopenic rat bones.

ObjectiveThis study aimed to explore the efficacy and safety of Bifidobacterium combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating depression in adolescents.MethodsA total of 100 patients were selected and divided into an experimental group (n = 50) and a control group (n = 50) using a random number table. Patients in the experimental group were treated with Bifidobacterium and high-frequency rTMS, and those in the control group were treated with oral escitalopram oxalate. After 8 weeks of treatment, the Hamilton Rating Scale for Depression (HAMD-24) score, serum inflammatory factors, neuroendocrine indicators and microRNAs were determined in both groups. The single-blind principle was strictly followed throughout the study.ResultsThe HAMD-24 score after treatment significantly decreased in the experimental group compared with the control group, with a statistically significant difference (p < 0.05). The levels of serum tumour necrosis factor-α, interleukin (IL)-1β and IL-6 also decreased significantly in the experimental group compared with the control group (p < 0.05). Additionally, the elevated levels of dopamine, serotonin and cortisol, including dopamine, 5-hydroxytryptamine and cortisol, was more pronounced in the experimental group than in the control group. The serum levels of miR-16 and miR-195 also showed statistically significant differences (p < 0.05).ConclusionBifidobacterium combined with high-frequency rTMS is effective in the treatment of depression in adolescents with a favourable safety profile, providing references for the clinical treatment of this disease.Clinical trial number: ISRCTN16752763 (https://doi.org/10.1186/ISRCTN16752763), Date: 19/03/2025.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12991-025-00595-5.

Objective: To explore the clinical application value and ideas of the collaborative mode of traditional Chinese and Western medicine based on syndrome differentiation and treatment in the treatment of complex schizophrenia. Methods: the diagnosis and treatment process of a 53 year old female patient with schizophrenia comorbid hyperthyroidism was reported in detail. The patient had a history of 25 years, was intolerant to a variety of antipsychotics and had repeated symptoms. A small dose of olanzapine (5mg/day) combined with escitalopram oxalate (10mg/day) was used. According to the syndrome differentiation of traditional Chinese medicine, the treatment was divided into three stages: the first diagnosis (liver depression and phlegm disturbance, heart and spleen deficiency) was treated with soothing liver depression, resolving phlegm and opening orifices, invigorating spleen and benefiting qi, and Chaihu Shugan powder combined with Wendan Decoction was used as the decoction; The second diagnosis (liver and kidney deficiency, spleen and stomach weakness) is to nourish the liver and kidney, strengthen the spleen and appetizer; Three diagnostic methods (deficiency Yang floating over, phlegm heat internal disturbance) are used to calm nerves, clear away heat and dissipate phlegm. Results: after treatment, the patients' positive symptoms such as hallucination and delusion disappeared, the hyperthyroidism related physical symptoms and drug side effects were significantly improved, and the condition was stable. Conclusion: this case shows that the dynamic syndrome differentiation of traditional Chinese medicine based on the principle of "corresponding prescriptions and syndromes" can effectively cooperate with western medicine, significantly improve the physical symptoms and drug side effects of patients while controlling mental symptoms, reflecting the synergistic advantages of traditional Chinese medicine and Western medicine of "dynamic syndrome differentiation, simultaneous treatment of physical diseases, synergy and detoxification".

Chronic stress induces mood disturbances, disrupts gut barrier function, and promotes low-grade systemic inflammation. This study assessed the therapeutic effects of atomoxetine (ATX), escitalopram (ESC), cannabidiol (CBD), and CBD-loaded lipid nanoparticles (CBD/LNP) in male rats exposed to repeated restraint stress. Stressed rats exhibited a 2.03-fold increase in interleukin-6 and a 1.89-fold increase in TNF-α, a 1.20-fold decrease in brain-derived neurotrophic factor, a 1.36-fold decrease in osteocalcin, accompanied by alterations in gut metabolites, particularly short-chain fatty acids (SCFAs; from 155.3 to 94.83 μmol/L), polyamines (from 273.6 to 192.4 μmol/L), and bile acids (BAs; from 21.19 to 14.53 μmol/L), compared with the control group. Protein analysis revealed gut barrier disruption and microglial/macrophage activation, accompanied by reduced synaptic plasticity. ATX improved gut permeability and reduced glial activation but did not restore osteocalcin. ESC provided neuroimmune benefits with limited and BA gut restoration and modulated the gut-brain axis and improved anxiety-like behaviors, partly by altering gut microbiota and metabolites. CBD and CBD/LNP treatment restored intestinal barrier function, as indicated by intestinal permeability in the range of 1.15-1.61-fold. These treatments also normalized bile acids (1.0-1.38-fold) and osteocalcin (1.0-1.28-fold) and significantly reduced glial activation (0.63-1.12-fold) as opposed to the non-treated stressed group. All treatments were found to be effective in correcting SCFA and polyamine levels. Histological analysis confirmed that CBD/LNP, ATX, and ESC ameliorated tissue alterations. These findings highlight CBD/LNP as a promising intervention for stress-induced gut-brain-bone axis disruption, supporting its potential as a therapeutic alternative through modulation of microbiota-driven gut-brain communication in stress-associated disorders.

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and anxiety, but their potential for drug-drug interactions (DDIs) poses significant risks, particularly given their influence on cytochrome P450 enzymes. Variability in identifying and classifying these interactions among drug interaction checkers (ICs) can complicate clinical decision-making and compromise patient safety. This study aims to compare five widely used ICs in identifying DDIs related to SSRIs, highlighting discrepancies in DDI identification and severity classification to inform best practices.MethodsA comparative study was conducted using five popular ICs (Micromedex, Lexi-Interact, Epocrates, Medscape, and Drugs.com) to evaluate their performance in identifying SSRIs-related DDIs. Data on drug-SSRIs interaction pairs were extracted over 2 weeks in 2025. Descriptive analysis was used to quantify potential interactions and their severity. Gwet’s AC1 coefficient was employed to assess agreement among all five ICs and to compare groups of four- and two-pair sets of ICs.ResultsA total of 1,190 potentially interacting drugs with fluoxetine (FXT) were reported, 1,129 for fluvoxamine (FVM), 1,131 for citalopram (CIT), 1,084 for paroxetine (PAR), 1,206 for sertraline (SER) and 1,146 for escitalopram (ESC). The agreement among all five ICs was notably low, with Gwet’s AC1 values ranging from 0.16 to 0.24 across different SSRIs. Similarly, it was poor in 4 and 2 sets analyses. The level of agreement among the ICs in classifying the severity of potential DDIs or restricting DDIs identified as severe was poor, also in 4 and 2 sets analysis.ConclusionThe findings reveal substantial discrepancies in the identification and severity categorization of SSRIs-related DDIs among ICs, underscoring the challenges faced by healthcare providers in ensuring safe prescribing practices. The study advocates for the standardization of IC databases and severity criteria to enhance consistency and reliability.

One of the major environmental and socioeconomic challenges todayis the improper disposal of stable pharmaceutical compounds. In thiscontext, this study focuses on the biosynthesis and characterizationof lithium oxide nanoparticles (Li2O-NPs) using Mentha arvensis extract for the adsorption-basedremoval of the escitalopram oxalate (OxE) drug from aqueous solutions.The nanoparticles were characterized by Fourier transform infrared(FTIR) spectroscopy, field emission gun scanning electron microscopy(FEG-SEM), N2 porosimetry, ζ-potential (ZP), thermogravimetricanalysis (TGA/DTG), and X-ray diffraction (XRD) to assess their textural,structural, morphological, and thermal properties. Moreover, their in vitro biocompatibility was evaluated using SH-SY5Y cells.Li2O-NPs exhibited mesoporous morphology with small particleclusters, characteristic peaks of the antifluorite crystalline phase,a negative surface charge, and functional groups consistent with Li2O. Cytotoxicity assays confirmed that the nanoparticles provideda biocompatible environment, causing no oxidative stress or inflammationwith the tested concentration range (1–150 μg mL–1). Regarding the adsorption equilibrium, analysisshowed that OxE adsorption onto Li2O-NPs followed the Hillmodel (qH = 38.96 mg g–1, KH = 0.0384 mg L–1, nH = 0.5582, R2 = 0.9975), indicating moderate affinity betweenthe adsorbate and nanoadsorbent. Kinetics studies revealed that thepseudo-first-order (PPO) model provided the best fit, with q1 = 130.7 mg g–1 and k1 = 0.0061 min–1, indicatingphysical adsorption as the predominant mechanism for the OxE removal.Therefore, Li2O-NPs demonstrated strong potential as ananoadsorbent for the treatment of water contaminated with stablepharmaceutical compounds.

A randomized controlled trial comparing mindfulness to escitalopram for anxiety: In-person and remote, synchronous delivery pre and post COVID-19 pandemic.

BackgroundObsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by obsessions and compulsions. Selective serotonin reuptake inhibitor (SSRI) is the first-line treatment with proven efficacy in controlled settings, which often necessitates higher SSRI doses than depression. In Japan, paroxetine (PXT), titrated up to 50 mg, offers dose flexibility but requires over five weeks for gradual titration in outpatient care. Escitalopram (ESP), limited to 20 mg, has a simpler schedule, allowing faster evaluation of efficacy and tolerability, despite its lower maximum dose. Although ESP is only approved for depression in Japan, it is widely used off-label for OCD, especially for childhood OCD.Aims & ObjectivesThis study sought to prospectively examine the comparative efficacy and tolerability comparing between paroxetine and escitalopram in routine outpatient settings.MethodThis study enrolled forty-two outpatients of our hospital who met DSM-5 criteria for OCD and gave us written informed consent to participate in this study. Twenty-two patients were randomly assigned to the PXT group, and twenty initially received ESP. PXT was initiated at 10 mg/day and titrated to a maximum of 50 mg/day with an interval of at least one week between dose increases, while ESP was started at 10 mg/day and increased to a maximum of 20 mg/day as tolerated. Treatment response was assessed 6–8 weeks after reaching the maximum tolerated dose, with an effective response defined as a ≥25% reduction in Yale Brown Obsessive Compulsive Scale (YBOCS) score. This study was approved by the Ethics Committee of Hyogo Medical University (Approval No. 2080).ResultsAt the beginning of this study, mean age of 35.2 (±10.4) in the PXT group and 33.3 (±11.9) in the ESP group and mean YBOCS total score of 28.8 (±6.7) and 27.6 (±6.6), respectively. The time to achieve the maximum tolerated dose was significantly longer in the PXT group, averaging 7.4 (±4.3) weeks, compared to 4.3 (±4.1) weeks in the ESP group (p < 0.01). In the PXT group, 8 patients (36.4%; 3 at 40 mg/day and 5 at 50 mg/day) showed an effective response, compared to 4 patients (20.0%; all at 20 mg/day) in the ESP group without statistically significant group-difference. Finally, 4 patients (18.2%) in the PXT group discontinued treatment due to side effects, while 5 patients (25.0%) in the ESP group discontinued.Discussion & ConclusionsPXT demonstrated a numerically higher treatment response rate compared to ESP, which may be attributed to its broader dosing range; however, this difference was not statistically significant. PXT’s extended titration schedule, often exceeding five weeks due to outpatient scheduling constraints, may delay therapeutic outcomes in routine clinical practice. In contrast, ESP’s simplified titration schedule allows for quicker evaluations of efficacy and tolerability, although its lower maximum dose may limit its overall effectiveness. These results highlight the need to balance pharmacological properties with practical considerations, such as treatment logistics, adherence and adverse effect, when selecting SSRIs for each OCD individual.

Objective: This study aimed to develop and optimize an Oral Thin Film (OTF) formulation of escitalopram oxalate to enhance patient compliance, improve drug acceptability, and facilitate rapid systemic absorption. Methods: A Central Composite Design (CCD) under Response Surface Methodology (RSM) was employed to optimize the formulation. Polymer (300–500 mg) and plasticizer (100–300 mg) concentrations were selected as independent variables, and their effects on critical response parameters—tensile strength, folding endurance, disintegration time, and dissolution rate-were evaluated. The optimized OTF was characterized for thickness, disintegration, and dissolution behaviour. Results: The optimal polymer and plasticizer concentrations were identified as 400 mg and 220 mg, respectively, yielding desirable film properties. The OTF thickness ranged from 0.48 to 0.57 mm, with formulations between 0.50 and 0.55 mm exhibiting the most favorable dissolution and disintegration profiles. The optimized OTF exhibited a tensile strength of 15.3 N/mm², folding endurance of 159 folds, and a disintegration time of 73 sec. Dissolution studies demonstrated 98% drug release within 10 min, confirming rapid dissolution for a fast onset of action. Conclusion: The study successfully developed an optimized OTF formulation of escitalopram oxalate, supporting the global shift toward patient-centric drug delivery. The formulation enhances therapeutic outcomes by ensuring rapid systemic absorption and improved patient adherence.

Major depressive disorder (MDD) is a significant global health issue, yet its pathophysiology remains unclear. One-third of patients achieve complete remission with monotherapy, highlighting the need for effective add-on therapies. This study explores the antidepressant potential of galantamine (GAL) as an add-on to escitalopram (ESC), focusing on the neurotrophic system, kynurenine pathway, neuroinflammation, and oxidative stress in MDD. We employed corticosterone (CORT)-induced toxicity in Neuro-2a cells and an unpredictable chronic mild stress (UCMS) model in mice to simulate depressive conditions. Neuro-2a cells were treated with GAL (39 µM) and ESC (107 µM) in CORT pretreated cells to better understand the protective potential of the drug combination. In vivo treatment with GAL (3 and 5mg/kg) and ESC (5 and 10mg/kg) for four weeks in UCMS mice was evaluated for behavioural, biochemical, and histopathological changes. The combination therapy enhanced cell viability, reduced apoptosis, and lowered intracellular ROS levels in Neuro-2a cells. In vivo, treatment with the GAL + ESC combination significantly alleviated UCMS-induced depressive symptoms and improved working memory. The combined therapy modulated the brain-derived neurotrophic factor (BDNF), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), TNF-α, and IL-6 levels, reversing oxidative stress markers in the hippocampus. Moreover, the combined therapy preserved hippocampal structure and modulated α7 nicotinic acetylcholine receptor (α7nAChR) density in the CA1 region of the hippocampus. This study signifies the potential of GAL as an add-on therapy to ESC, enhancing antidepressant effects and cognitive function, warranting further clinical investigation for treating depressive disorders.

Overall, 20% of patients with major depressive disorder (MDD) are treatment-resistant and do not respond to multiple antidepressant monotherapies. For such patients, augmentation therapy with antipsychotics is one of the therapeutic options. However, the mechanism of augmentation therapy is essentially unknown. This study aimed to elucidate the mechanism of brexpiprazole (BREX) augmentation at gene expression levels. Vehicle, escitalopram (ES), BREX, and ES + BREX (augmentation therapy) were administered to mouse neuroblastoma (Neuro2a) cells and submitted to RNA-sequencing. Gene expressions were also measured in the whole blood of MDD patients and the frontal cortices and hippocampi of mice after treatment for 20 days. On RNA-seq and gene ontology analyses, upregulation of mitochondria (MT)-related genes was confirmed by quantitative Polymerase Chain Reaction (PCR). These upregulated genes were successfully validated in both Neuro2a and Caco2 cells. Decreased MT-ATP8 expression was found in the whole blood of MDD patients. Furthermore, changes in MT-mRNA expression were confirmed in the frontal cortices and hippocampi of mice with augmentation therapy. BREX augmentation modified MT-mRNA expressions in both in vitro and in vivo experiments. This may be a key finding in improving our understanding of MDD pathogenesis and clinical practice.

Background: Antidepressants are a class of pharmaceuticals utilized for the management of many psychiatric disorders, including depression. A considerable number of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), have been documented to demonstrate significant anticancer properties in various cancer cell lines. Objectives: The aim of this study was to evaluate the selective cytotoxic and apoptotic effects of escitalopram oxalate (ES) alone and in combination with etoposide (ET) on ET-resistant A549 (A549/90E) lung cancer cells. Methods: The cytotoxic effects of the drugs were determined by CCK-8, trypan blue, and neutral red assays. Apoptosis was observed by Annexin V fluorescein isothiocyanate (FITC)/PI and mitochondrial membrane potential (ΔΨm) assays. Moreover, the effects of the drugs, alone and in combination, on apoptosis-related proteins, caspase-3, PTEN, and resistance-related P-gP were determined by ELISA. The relationship between drugs and lung cancer was determined with protein-protein interaction (PPI) network analysis. Results: Our results revealed that ES significantly exerted cytotoxic effects on both wild-type and A549/90E cells compared with BEAS-2B cells. The IC50 values of 48.67 and 51.6 μg/mL obtained for ET and ES, respectively, at the end of 24 h of incubation for A549 cells were applied reciprocally for each cell by including BEAS-2B together with the 2xIC50 and ½ IC50 values. The results of each combination were statistically evaluated with combination indices (CIs) obtained using the Compusyn synergistic effect analysis program. Combination doses with a synergistic effect in A549 and A549/90E cells and an antagonistic effect in BEAS-2B cells have been determined as ½ IC50 for ET and ½ IC50 for ES. ET ½ IC50, ES ½ IC50, and an ET ½ IC50 + ES ½ IC50 combination caused 18.37%, 55.19%, and 57.55% death in A549 cells, whereas they caused 44.9%, 22.4%, and 51.94% death in A549/90E cells, respectively. In A549 cells, the combination of ES ½ IC50 and ET ½ IC50 caused increased levels of caspase-3 (p < 0.01) and P-gP (p < 0.001), while PTEN levels remained unchanged. The combination resulted in an increase in caspase-3 (p < 0.001) and PTEN (p < 0.001) amounts, alongside a decrease in P-gP (p < 0.01) levels in A549/90E cells. The death mechanism induced by the combination was found to be apoptotic by Annexin V-FITC and ΔΨm assays. Conclusions: Based on our findings, ES was observed to induce cytotoxic and apoptotic activities in A549/90E cells in vitro. ES in combination therapy is considered to be effective to overcome ET resistance by reducing the amount of P-gP in A549/90E cells.

This analysis observed the clinical effect of acupuncture combined with Escitalopram oxalate in the treatment of mild to moderate post-stroke depression (PSD). This was a retrospective study of 1:1 matching design. A total of 96 cases of mild to moderate PSD patients were enrolled and divided into 48 cases each in the control group and the observation group. The control group received treatment with Escitalopram oxalate tablets. The observation group received acupuncture combined with Escitalopram Oxalate, both for a duration of 8weeks. Comparisons were performed in regard clinical efficacy, 17-Item Hamilton Rating Scale for Depression (HAMD-17), National Institutes of Health Stroke Scale (NIHSS), Pittsburgh Sleep Quality Index (PSQI), Barthel Index, neurotransmitters (5-hydroxytryptamine [5-HT], norepinephrine [NE], and dopamine [DA]), and liver function (alanine aminotransferase [ALT], aspartate transaminase [AST], direct bilirubin [DBIL], and total bilirubin [TBIL]). The Side Effect Rating Scale (SERS) scores at weekends 4 and 8 of treatment were counted. The total effective rate was 91.67% (44/48) higher for the observation group than 75.00% (36/48) for the control group (P < 0.05). HAMD-17, NIHSS, and PSQI scores decreased in the two groups after treatment, and they were all lower in the observation group than in the control group (P < 0.05). The observation group had a higher Barthel index than the control group (P < 0.05). Serum 5-HT, NE and DA levels increased in both groups after treatment, and serum markers were higher in the observation group compared with the control group (P < 0.05). The differences in SERS scores between the two groups were not significant (P > 0.05). Combining acupuncture with Escitalopram oxalate proves to be effective and safe for treating mild-to-moderate PSD, significantly alleviating depression, and enhancing neurological function, sleep quality, and quality of life.