Search Results (272)

Behavioral issues in domestic dogs represent a significant welfare concern affecting both canines and their caregivers, with prevalence rates reported to range from 34 to 86% across the population. Current treatment options, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, often present limitations including adverse effects and delayed efficacy. This randomized, placebo-controlled (maltodextrin) study investigated the effects of a novel Lactiplantibacillus plantarum strain (LP815^TM) on canine behavioral concerns through gut–brain axis modulation. Home-based dogs (n = 40) received either LP815^TM (n = 28) or placebo (n = 12) daily for 4 weeks, with behavioral changes assessed using the comprehensive Canine Behavioral Assessment & Research Questionnaire (C-BARQ) and continuous activity monitoring. After the intervention period, dogs receiving LP815^TM showed significant improvements in aggression (p = 0.0047) and anxiety (p = 0.0005) compared to placebo controls. These findings were corroborated by objective activity data, which demonstrated faster post-departure settling, reduced daytime sleep, and improved sleep consistency in the treatment group. Throughout >1120 administered doses, no significant adverse events were reported, contrasting favorably with pharmaceutical alternatives. The concordance between our findings and previous research using different L. plantarum strains suggests a consistent biological mechanism, potentially involving GABA production and vagal nerve stimulation. These results indicate that LP815^TM represents a promising, safe alternative for addressing common canine behavioral concerns with potential implications for improving both canine welfare and the human–animal bond. Full article

Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article

Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. Objectives: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. Methods: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. Results: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω₀₂₅ = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω₀₂₅ = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. Conclusions: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. Full article

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article

Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic unpredictable mild stress (CUMS)-induced changes in lymphoid organs through evaluating its effect on the histological structure of spleen, thymus gland, and lymph nodes compared to the antidepressant fluoxetine (FLU). Materials and Methods: Fifty male albino rats equally distributed into five groups that included control, control + CP, CUMS-exposed, FLU-treated, and CP-treated groups were used in this study. Rats were exposed to CUMS for 4 weeks, and treatment (either with FLU or CP) was started after 14 days of exposure. Behavior of the rats, serum corticosterone, oxidants/antioxidants profile, proinflammatory cytokines, and gene expression of glucocorticoid receptor (GR) and β-adrenergic receptor (β2-AR) were assessed after 28 days. Spleen, thymus gland, and lymph nodes were histopathologically assessed. Results: CP administration significantly reduced the CUMS-induced behavioural changes evident by the significant reduction in immobility time (p = 0.02) and corticosterone level (p < 0.001). Biochemically, CP reduced TNF-α and IL-6 (p < 0.001) and markedly alleviated the changes in oxidants/antioxidants in the serum and lymphoid organs compared to fluoxetine. CP significantly (p < 0.001) reduced CUMS-induced changes in GR and (β2-AR). Histopathologically, CP alleviated changes observed in the spleen, lymph nodes, and thymus gland. It significantly reduced the number of CD4, CD8, CD68, CD20, and caspase-3 immunopositive cells in the studied organs. Conclusions: This study proved the potential efficacy of CP in alleviating depression-associated immunodysregulation either alone or in combination with antidepressant therapy. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Pharmaceuticals such as fluoxetine, paroxetine, sertraline, and mianserin occur in aquatic environments at low yet persistent concentrations due to their incomplete removal in wastewater treatment plants. Although frequently detected, these neuroactive compounds remain underrepresented in ecotoxicological assessments. Given their pharmacodynamic potency, environmentally relevant concentrations may induce sublethal effects in non-target organisms. In this study, we applied untargeted LC-MS-based metabolomics to investigate the sublethal effects of four widely used antidepressants—paroxetine, sertraline, fluoxetine (SSRIs), and mianserin (TeCA)—on two ecologically relevant freshwater invertebrates: S. ambiguum and D. magna. Organisms were individually exposed to each compound for 48 h at a concentration of 100 µg/L and 25 µg/L, respectively. Untargeted metabolomics captured the sublethal biochemical effects of these antidepressants, revealing both shared disruptions—e.g., in glycerophospholipid metabolism and cysteine and methionine metabolism—and species-specific responses. More pronounced pathway changes observed in D. magna suggest interspecies differences in metabolic capacity or xenobiotic processing mechanisms between taxa. Among the four antidepressants tested, sertraline in D. magna and fluoxetine in S. ambiguum exerted the most extensive metabolomic perturbations, as evidenced by the highest number and pathway impact scores. In D. magna, fluoxetine and mianserin produced similar metabolic profiles, largely overlapping with those of sertraline, whereas paroxetine affected only a single pathway, indicating minimal impact. In S. ambiguum, paroxetine and mianserin elicited comparable responses, also overlapping with those of fluoxetine, while sertraline triggered the fewest changes. These results suggest both compound-specific effects and a conserved metabolic response pattern among the antidepressants used. They also underscore the considerable potential of metabolomics as a powerful and sensitive tool for ecotoxicological risk assessments, particularly when applied across multiple model organisms to capture interspecies variations. However, further research is essential to identify which specific pathway disruptions are most predictive of adverse effects on organismal health. Full article

Background/Objectives: Hepatic clearance is important in determining clinical drug administration strategies. Achieving accurate hepatic clearance predictions through in vitro-to-in vivo extrapolation (IVIVE) relies on appropriate model selection, which is a critical step. Although numerous models have been developed to estimate drug dosage, some may fail to predict liver drug clearance owing to inappropriate hepatic clearance models during IVIVE. To address this limitation, an in silico-based model selection approach for optimizing hepatic clearance predictions was introduced in a previous study. The current study extends this strategy by verifying the accuracy of the selected models using ex situ experimental data, particularly for drugs whose model choices are influenced by protein binding. Methods: Commonly prescribed drugs were classified according to their hepatic extraction ratios and protein-binding properties. Building on previous studies that employed multinomial logistic regression analysis for model selection, a three-phase classification method was implemented to identify five representative drugs: diazepam, diclofenac, rosuvastatin, fluoxetine, and tolbutamide. Subsequently, an isolated perfused rat liver (IPRL) system was used to evaluate the accuracy of the in silico method. Results: As the unbound fraction increased for diazepam and diclofenac, the most suitable predictive model shifted from the initially preferred well-stirred model (WSM) to the modified well-stirred model (MWSM). For rosuvastatin, the MWSM provided a more accurate prediction. These three capacity-limited, binding-sensitive drugs conformed to the outcomes predicted by the multinomial logistic regression analysis. Fluoxetine was best described by the WSM, which is consistent with its flow-limited classification. For tolbutamide, a representative capacity-limited, binding-insensitive drug, no significant differences were observed among the various models. Conclusions: These findings demonstrate the accuracy of an in silico-based model selection approach for predicting liver metabolism and highlight its potential for guiding dosage adjustments. Furthermore, the IPRL system serves as a practical tool for validating the accuracy of the results derived from this approach. Full article

Shallow lakes are highly vulnerable to pollution due to their small water volume. Those that receive effluent from the drainfields of onsite wastewater treatment systems (septic tanks) may contain pharmaceuticals and personal care products (PPCPs) that escaped removal during treatment. This study examined the effects of seasonal rainfall variability on the assemblages and concentrations of fourteen PPCPs in two shallow lakes in West–Central Florida, USA: one surrounded by residents equipped with septic tanks and the other located within a nature preserve. Water samples were collected weekly during an 18-week interval from April to August 2021. Liquid chromatography–mass spectrometry analyses revealed the omnipresence of five PPCPs: theophylline, caffeine, cotinine, DEET, and testosterone, although acetaminophen, ibuprofen, and sulfamethoxazole were also common. Of all the PPCPs detected, theophylline, DEET, and acetaminophen concentrations were higher during the wet season in the septic tank-influenced lake, while caffeine, cotinine, and testosterone concentrations decreased. In the lake located in the nature preserve, theophylline, caffeine, and acetaminophen levels increased in the wet season. In contrast, cotinine, DEET, and testosterone levels decreased. Overall, more compounds were detected during the wet season, with highly hydrophobic PPCPs (fluoxetine, atorvastatin, and octocrylene) only present during this period. Full article

Backgrounds and Objectives: This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Materials and Methods: Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs. Sensitivity analysis was performed to validate the overall findings and assess the robustness of associations across subgroups defined by completeness of demographic data (age and sex), elderly age-stratification, and causality assessment. The study protocol was approved by the Kyung Hee University institutional review board. Results: Among 21,103 antidepressant-related ADEs, duloxetine was the most etiologic medication, followed by amitriptyline and escitalopram. Fluoxetine is the only agent with a high likelihood of reporting SAEs. ADEs involving vascular (extracardiac) disorders (ROR 42.42, 95% CI 13.19–136.42) and liver and biliary system disorders (ROR 7.84, 95% CI 3.77–16.29) were most likely to be SAEs. The predictors associated with substantial increased SAE risk were fluoxetine use (OR 2.71, 95% CI 1.68–4.39), male sex (OR 1.48, 95% CI 1.11–1.98), and concomitant administration of antiparkinsonian treatment (OR 8.29, 95% CI 3.61–19.06) and antidementia treatment (OR 2.94, 95% CI 1.34–6.05). Sensitivity analyses demonstrated similar and consistent findings. However, reversed trends in the association between SOC-based ADEs and sex were observed in the sensitivity analysis restricted to cases with “certain” and “probable” causality. Conclusions: The type of antidepressant, concomitant medications, and sex are major predictors for SAE risk. Further controlled studies on the impact of comorbidities and polypharmacy on antidepressant-related SAEs are warranted. Full article

Background/Objectives: Depression ranks among the most prevalent mental health conditions globally, marked by a variety of symptoms that frequently cause significant emotional distress and impairment in individuals, alongside a high recurrence rate. The predominant approach to treating depression revolves around monoamine theory, utilizing SSRIs and SNRIs, with Esketamine emerging as a supplementary option in recent times. Nevertheless, there is a growing focus on exploring the relationship between inflammation and depression, revealing a strong correlation between the two. This insight prompts consideration of the anti-inflammatory properties of current antidepressants in their therapeutic application. Methods: A systematic literature search was conducted using the PubMed database to identify randomized controlled trials (RCTs) and clinical trials (CTs) that assessed the in vivo anti-inflammatory effects of SSRIs (fluoxetine, escitalopram, sertraline, and paroxetine), the SNRI venlafaxine, and esketamine/ketamine in human subjects undergoing treatment for depression. The included studies were evaluated based on changes in levels of pro-inflammatory and anti-inflammatory markers in response to the antidepressant treatments. Results: SSRIs, SNRIs, esketamine, and ketamine (a racemic mixture of S- and R-ketamine not formally approved for the treatment of depression) exhibit anti-inflammatory effects through diverse mechanisms, such as reducing pro-inflammatory cytokines or enhancing anti-inflammatory cytokines in serum or within specific brain regions like the hippocampus and prefrontal cortex. These actions are mediated through various inflammatory pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome, the glutamatergic system, the gut–brain axis, the hypothalamic–pituitary axis, impaired neuroplasticity, and the kynurenine pathway. Conclusions: In summary, SSRIs, SNRIs, esketamine, and ketamine exert an anti-inflammatory role alongside their antidepressant effects via these intricate mechanisms. Full article

Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. Methods: A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. Results: Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms—especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. Conclusions: High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies—such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms—may support more individualized and safer treatment strategies. Full article

Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in PD and to identify novel drug combinations that may target dysregulated molecular mechanisms associated with PD’s pathophysiology. Methods: We analyzed clinical records from 702 PD patients spanning 30 years, encompassing over 5500 prescription points. Using network-based modeling techniques, we assessed drug co-prescription patterns, clinical outcomes, and longitudinal treatment trends. To explore potential drug repurposing opportunities, we constructed a molecular network model of PD based on a consolidated transcriptomics dataset and integrated this with drug–target interaction information. Results: We found commonly prescribed drugs such as furosemide, sucroferric oxyhydroxide, calcitriol, darbepoetin alfa, and aluminum hydroxide to be integral components of PD patient management, prescribed in over 30% of PD patients. The molecular-network-based approach found combinations of drugs like theophylline, fluoxetine, celecoxib, and amitriptyline to possibly have synergistic effects and to target dysregulated molecules of PD-related pathomechanisms. Two further distinct categories of drugs emerged as particularly interesting in our study: selective serotonin reuptake inhibitors (SSRIs), which were found to modulate molecules implicated in peritoneal fibrosis, and vascular endothelial growth factor (VEGF) inhibitors, which exhibit anti-fibrotic properties that are potentially useful for PD. Conclusions: This comprehensive exploration of drug co-prescriptions in the context of PD-related pathomechanisms provides valuable insights for opening future therapeutic strategies and identifying new targets for drug repurposing. Full article

This study analyzed 97 pharmaceuticals in samples of surface water, as well as influent and effluent from various wastewater treatment plants (WWTPs), during winter 2022 and spring 2023. Approximately 40% of the tested compounds were detected, at amounts ranging from below the methods’ detection limits to 5623 ng/L (2-hydroxyibuprofen in surface water) and 12,664 ng/L (caffeine in wastewater). Twelve compounds (acetaminophen, ampicillin, azithromycin, caffeine, fluoxetine, gemfibrozil, 2-hydroxyibuprofen, ibuprofen, ketoprofen, mazindol, naproxen, and salicylic acid) were detected with a 100% frequency in both surface water and wastewater samples. The observed high detection frequency of pharmaceuticals within the nonsteroidal anti-inflammatory drugs/analgesics, antibiotics, and psychiatric drug classes aligns with their high consumption. Caffeine was both the compound with the highest concentration and the most prevalent compound detected. Seasonal differences were observed, with higher concentrations detected during winter. Six of the eleven targeted metabolites and degradation products were detected in at least one sample. Risk quotient assessment revealed potential ecological risks, particularly for atorvastatin, caffeine, carbamazepine, and venlafaxine, exceeding risk thresholds for various trophic levels. The studied WWTPs showed limited removal efficiencies, with some compounds presenting higher concentrations in effluent than in influent, emphasizing the need for enhanced treatment to mitigate micropollutant risks. Full article

Selective serotonin reuptake inhibitors (SSRIs), like fluoxetine, are increasingly used by women of a reproductive age, raising concerns about their impact on oocyte quality and early embryonic development. This study investigated the effects of chronic fluoxetine exposure on oocyte maturation, ovulation, and embryonic development in a mouse model. Female mice were administered fluoxetine via drinking water, and their reproductive outcomes were compared to those of control mice. Oocyte quantity and quality were assessed following superovulation, including the analysis of spindle morphology, chromatin configuration, and maturation markers. In vitro maturation assays were conducted to evaluate the developmental competence of oocytes exposed to fluoxetine. Finally, the impact of fluoxetine on blastocyst formation, litter size, offspring growth, and ovarian reserve was examined. The results show that fluoxetine treatment reduced the number of ovulated oocytes but did not significantly affect oocyte quality or meiotic spindle formation. Fluoxetine exposure impaired cytoplasmic maturation at the germinal vesicle stage, resulting in a lower proportion of fully mature oocytes and reduced in vitro maturation efficiency. While blastocyst numbers were modestly reduced in fluoxetine-treated mice, litter size and offspring ovarian reserve were unaffected. Unexpectedly, offspring of fluoxetine-treated mothers exhibited increased body weight. These findings suggest that while fluoxetine may impair oocyte developmental competence through disruptions in cytoplasmic maturation, it does not severely compromise overall reproductive outcomes or offspring fertility. Full article