Selective serotonin reuptake inhibitors (SSRIs) are reported to be implicated in altering glucose homeostasis and inducing hypoglycemia in diabetic patients and mice. Herein, the effects of paroxetine on glucose homeostasis, insulin secretion, and insulin sensitivity were investigated in both healthy and streptozotocin-induced-insulin deficient mouse model. Mice were administered with paroxetine (1, 10, and 50 mg/kg) and fasting insulin levels and glucose-stimulated insulin secretion were assessed in healthy mice, whereas the glycemic profile in diabetic mice was evaluated after glucose or insulin challenge. Muscle mRNA expression of insulin signaling-relevant genes was analyzed, in addition to protein kinase B (PKB/Akt) activity and glucose transporter 4 (GLUT4) plasma membrane expression assessed in C2C12 myotubes. Paroxetine modulated glucose homeostasis and reduced the spike in blood glucose in diabetic mice in a dose-dependent manner after a glucose tolerance test. On the other hand, a reverse relationship was observed in the insulin tolerance test, with no evidence of acute hypoglycemia, suggesting that paroxetine did not further exacerbate insulin-induced glucose lowering under the tested conditions. Paroxetine (50 mg/kg) significantly increased fasting insulin secretion and upregulated genes involved in insulin receptor and Akt signaling, while reducing Glut4 mRNA expression. At 10 mg/kg, paroxetine significantly elevated Akt phosphorylation (p < 0.01). Paroxetine enhanced GLUT4 translocation and Akt phosphorylation in C2C12 myotubes. These findings suggest that paroxetine influences glucose homeostasis in diabetic conditions without causing acute hypoglycemia. Nevertheless, further preclinical and clinical investigations are warranted to clarify its metabolic effects and to determine the clinical implications for glycemic management in diabetic patients receiving paroxetine.

Beta-adrenoreceptor blockers (beta-blockers) and selective serotonin reuptake inhibitors (SSRIs) are commonly used medications and often used together, such as for the treatment of anxiety. However, there is no recent review of any potential adverse events related to concomitant use of medicines from each group. This scoping review therefore aimed to provide this narrative synthesis. Key databases were searched for articles published in English from 1 January 1990 to 24 November 2025 reporting any adverse event due to the concomitant use of beta-blockers and SSRIs in people aged 18 or over. Any study design was permitted. From 2211 distinct records, 117 articles were eligible for full-text screening, and 48 articles were included. Eight of these were review articles referring to otherwise-included empirical studies. Most were interventional (n = 19, 36.9%) or case reports (n = 14, 29.2%). Bradycardia was the most frequently reported adverse event (n = 11) mostly in case reports involving metoprolol-fluoxetine, metoprolol-paroxetine, metoprolol-sertraline or propranolol-fluoxetine. Blood pressure changes (including hypotension) were observed in half of studies which explored them. Neurocognitive-related symptoms were heterogeneous and there were four case reports/series of self-poisoning suicide or self-harm. The adverse events discussed in this review could be signals for drug-drug interactions. Where mechanism was postulated, authors mostly proposed pharmacokinetically mediated effects via Cytochrome P450 2D6. Signals described in this review of potential adverse events should be examined in robust observational studies of specific beta-blocker-SSRI combinations. This will enable precise estimation of the magnitude of any associated risks and provide insight into the potential mechanism.

The American College of Physicians (ACP) developed this clinical guideline on pharmacologic treatments for internal medicine physicians and other clinicians caring in outpatient settings for females with menopausal vasomotor symptoms.

Serotonin transporter (SERT), encoded by SLC6A4, is a key regulator of serotonergic neurotransmission and a primary target for selective serotonin reuptake inhibitors (SSRIs). Dysregulation of SERT is implicated in neuropsychiatric and neurodevelopmental disorders, including autism spectrum disorder (ASD). SSRIs, while widely used, have limitations such as adverse effects, drug-drug interactions, and interindividual variability, necessitating safer and mechanistically distinct SERT modulators. This study utilized an integrative in-silico approach to evaluate the SERT inhibitory potential of glabridin, glabrene, and liquiritigenin the phytoestrogens from Glycyrrhiza glabra (licorice), known for neuroprotective properties. Blind and site-specific molecular docking, molecular dynamics simulations, binding free energy calculations, ADMET profiling, and machine learning-based QSAR modeling were employed to characterize ligand-transporter interactions. The compounds glabridin and glabrene exhibited favorable binding affinity for the central S1 substrate-binding site of human SERT, with a comparable or superior binding free energy (-50.35 kcal/mol and -52.41 kcal/mol, respectively) to the reference SSRI paroxetine (-53.04 kcal/mol). The 100 ns MD simulations confirmed stable ligand occupancy and persistent interactions with key residues involved in extracellular gate regulation, stabilizing the SERT outward-open inhibitory conformation. ADMET predictions indicated favorable pharmacokinetic properties, including blood-brain barrier permeability and acceptable toxicity profiles of glabridin and glabrene. QSAR-derived IC50 estimates and combination modeling revealed nonantagonistic, mild positive cooperativity between glabridin and glabrene, supported by dual-ligand docking and MM-GBSA analyses, suggesting complementary orthosteric engagement. These findings position glabridin and glabrene as putative natural SERT modulators, providing a mechanistic basis for their potential use in serotonergic modulation therapeutics, warranting further experimental validation.

Catheters are often sources of bloodstream infections since they promote the development of polymicrobial biofilms composed of Candida albicans and Staphylococcus aureus, which are resistant to conventional treatments. Paroxetine (PRX), a selective serotonin reuptake inhibitor, has demonstrated antibiofilm activity against both C. albicans and S. aureus. However, studies evaluating PRX's activity against polymicrobial biofilms remain scarce. Consequently, we investigated the activity of PRX against mixed biofilms of C. albicans and S. aureus, as well as its potential to prevent the formation of such biofilms on peripheral venous catheters. Our findings revealed that PRX not only prevented biofilm formation but also significantly reduced both the viability and biomass of these structures, possibly by disrupting the polysaccharide matrix. When impregnated in peripheral venous catheters, PRX also inhibited the excessive growth of microbial communities, making it a potentially effective agent to modulate the structure and susceptibility of multispecies biofilms, expanding its spectrum of action to more complex clinical scenarios associated with medical devices.

The coexistence of multiple primary sleep disorders in a single patient is uncommon and poses significant diagnostic and therapeutic challenges. We report a 45-year-old woman with severe mixed sleep apnea (OSA/CSA), NREM parasomnia (night terrors), sleep-related eating disorder (SRED), nightmare disorder (with RBD like behavior but no REM atonia on PSG), and central hypersomnolence phenotype minimally affected with PAP optimization and delayed sleep-wake phase disorder. Symptoms began more than two decades earlier and included violent dream-enactment behaviors, hypnopompic hallucinations, sleep inertia, and chronic excessive daytime sleepiness (EDS). Treatment required multi-modal therapy. Positive airway pressure therapy successfully treated sleep disordered breathing while pitolisant and solriamfetol produced the most durable improvement in daytime sleepiness. Together melatonin plus clonazepam reduced parasomnia frequency and severity. Several other agents (including prazosin, sodium oxybate, paroxetine, and modafinil) were tried and discontinued for limited benefit or adverse effects. Notably, GLP-1 receptor agonist (GLP-1 RA) therapy for obesity was followed by a substantial weight loss and coincided with resolution of SRED. Because this occurred alongside improved sleep stability, PAP adherence, behavioral adaptation, and medication changes, causality cannot be inferred. The observation may justify further study of metabolic and incretin-related pathways in sleep-related eating behaviors. Overall, this case highlights the complexity of overlapping sleep-wake disorders, the need for individualized pharmacologic sequencing, and a potential emerging role for GLP-1 agonists in SRED.

This case report examines the presentation and management of late-onset frontal lobe syndrome (FLS) following early-life traumatic brain injury (TBI). It illustrates the diagnostic challenges of this condition and the rationale for an individualized pharmacological approach. The case focuses on a young adult male who sustained two head injuries in early childhood, the more severe being a frontotemporal trauma at age 5, with debilitating FLS symptoms, including marked emotional lability and executive function deficits, emerging at age 17. This delayed presentation, characteristic of late-onset FLS, often complicates diagnosis and treatment. Prior to referral, the patient experienced significant interpersonal conflicts, strained family dynamics, and an inability to maintain employment due to his FLS symptoms. Recognizing the profound impact of his condition, a tailored pharmacological intervention strategy was implemented, focusing on mood stabilization and emotional regulation. This approach utilized mood stabilizers, specifically lithium and valproic acid, alongside the selective serotonin reuptake inhibitor (SSRI) paroxetine. Over follow-up, the patient demonstrated gradual improvements across multiple domains. His emotional lability decreased, alongside improved interpersonal relationships, reduced family conflict, and a greater capacity for sustained occupational engagement. Additionally, he reported subjective improvements in his overall quality of life, experiencing greater emotional well-being and increased self-efficacy. This case highlights the importance of considering long-term neurological consequences of TBI, even in the absence of immediate symptoms. It also illustrates the potential value of tailored pharmacological management within a broader multidisciplinary approach.