Search Results (326)

Background: Biological sex contributes to variability in drug metabolism, receptor sensitivity, and susceptibility to adverse drug reactions (ADRs). Despite this, dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) are still largely sex-neutral. This systematic review examines sex-related differences in pharmacokinetics (PK), pharmacodynamics (PD), and safety outcomes, with the aim of clarifying their potential implications for personalized psychopharmacology. Methods: A systematic search of PubMed was conducted for studies published between January 2010 and March 2026. The strategy combined MeSH terms and free-text keywords related to SSRIs, SGAs, sex differences, pharmacokinetics, pharmacodynamics, and ADRs. Two independent reviewers performed study selection and data extraction. Studies reporting sex-stratified PK, PD, or safety outcomes in humans were included. Owing to methodological heterogeneity, results were synthesized narratively. Results: Twenty-seven studies met the inclusion criteria. Overall, the evidence indicates clinically meaningful sex-related differences in psychotropic drug exposure and response. Women more frequently exhibited higher dose-adjusted serum concentrations, particularly for risperidone and some SSRIs, with age-related increases more evident in females. Pharmacodynamic findings suggest that women may reach comparable dopamine D2 receptor occupancy at lower olanzapine doses. Pharmacovigilance analyses revealed sex-specific adverse event patterns, including greater reporting of endocrine-related effects and QT prolongation in women. Conclusions: Sex influences psychotropic drug exposure, pharmacodynamic sensitivity, and safety profiles in ways that may be clinically relevant. Integrating sex-aware considerations into dosing strategies could improve therapeutic precision and reduce adverse outcomes, reinforcing the importance of sex as a key variable in personalized psychiatric care. Full article

Obsessive-compulsive disorder (OCD) is a chronic mental disorder characterized by distressing thoughts and repetitive behaviors that significantly impair daily functioning and quality of life. Many patients fail to achieve sufficient symptom relief with first-line treatments, such as cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs). Dopaminergic dysregulation has been implicated in the pathophysiology of OCD, providing a rationale for pharmacological augmentation strategies. This article presents a narrative review of the evidence regarding the efficacy, safety, and clinical applicability of antipsychotic agents and emerging pharmacological augmentation approaches, including extended-release methylphenidate (MPH-ER), in SSRI-resistant OCD. A literature search was conducted using PubMed, EBSCO, and Embase databases, with an additional search of Google Scholar, focusing on studies examining pharmacological augmentation in treatment-resistant OCD. Overall, the evidence base is limited by small sample sizes, short follow-up durations, heterogeneous response criteria, and a lack of head-to-head comparisons versus CBT augmentation, which constrains the generalizability of conclusions. Dopamine receptor antagonists, particularly risperidone, as well as the partial agonist aripiprazole, remain the most consistently supported augmentation strategies, while olanzapine and quetiapine may be considered in selected cases. Evidence for MPH-ER is currently limited—supported by one small RCT and two recent case series—and may be considered in carefully selected adults with comorbid ADHD or marked executive dysfunction, although larger controlled studies and long-term safety data are required before firm clinical recommendations can be made. Full article

When using traditional approaches, such as pharmacokinetics and pharmacodynamics, the entire cellular or molecular response to drugs in the body cannot be fully ascertained or established. The oral medication process involves pharmacokinetics, followed by oral microbiomics and then gut microbiomics and pharmacodynamics. Recently, there has been increasing interest in the role of genetics (pharmacogenetics and pharmacogenomics) in both humans and microbiomes, as well as omics alterations (e.g., epigenetic, transcriptomic, proteomic, and metabolomic alterations as a consequence of drug exposure), which can help to ascertain the cellular responses to medications. Both the efficacy and toxicity of a drug are influenced by these factors. To assess these at an individual level, an integrative Personalized Medicine Model may be needed to help with medication management. Two example application cases for SSRIs and statins demonstrate the clinical usefulness of such a model, which can guide clinicians during drug selection and dosing to reduce reliance on trial-and-error, thus potentially improving patient outcomes and safety. Integrating this framework into practical clinical workflows requires the capture, analysis, and translation of multi-omics data in order to realize decision support protocols and actionable drug recommendations. This review also discusses IT requirements and different stakeholder roles. Although the proposed model can guide the treatment of diseases at the individual patient level, further research is still needed before it can be implemented as part of drug development research, clinical care, and healthcare delivery systems. Full article

This study looks at a selection of newspaper content from 1995 to 2024 that mentions the names of SSRI drugs in passing as jokes, metaphors, or cultural references. These passing mentions of SSRIs are analyzed via qualitative textual analysis, considering stigma and trivialization. The results of the study suggest that stereotypes about SSRIs have been cemented via popular discourse and media coverage and persist today despite nearly 40 years of prescriptions. Mentions of the SSRI drugs in passing suggest the illusion of a post-Prozac society where mental illness has been “fixed” and therefore can be trivialized with little consequence. This work expands upon existing theoretical concepts to propose a new theoretical model—a continuum of trivialization and stigma which may aid researchers in parsing the ways that colloquialization, trivialization and stigma interact and overlap in media texts. Full article

Introduction: Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and a reduced ability to understand mental states (mentalization). These features can lead to suicidal ideation and/or behavior. Intranasal esketamine may offer a novel therapeutic option for this population. Methods: This case series focuses on the clinical response to intranasal esketamine in patients with autism and TRD; esketamine is approved in Italy as an add-on therapy in TRD, so our case study is based on an in-label treatment. Three young patients (n = 3, F/M 2:1, age range 20–25 y) with light to moderate autism (Level 1 or 2) were treated. Esketamine was administered in augmentation with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in accordance with EMA/AIFA guidelines. A structured follow-up protocol was set to monitor depressive symptoms, social cognition, and mentalization. Follow-up during treatment was maintained for six months, and psychometric evaluations were performed at six time points: baseline (T0), 1 week (T1), 1 month (T2), 2 months (T3), 3 months (T4), and 6 months (T5). Also, subjective quality of life was investigated before and after the observation period. Results: Despite differences in clinical profile, all patients showed good efficacy of esketamine in reducing depressive symptoms: two patients experienced clinical remission at T5 (MADRS < 10), one patient showed partial response (dMADRS = 43.24%). No major side effects were reported. Significant improvements were observed after the first week of treatment (P1: MADRS_T0 = 37, MADRS_T1 = 12; P2: MADRS_T0 = 32, MADRS_T1 = 21; P3: MADRS_T0 = 25, MADRS_T1 = 12). Depressive relapses occurred (e.g., P1, T3–T4), but they were not associated with hospitalizations and/or suicidal attempts. Suicidal ideation, when present, decreased by the end of the follow-up period. Lack of mentalization and in social cognition was noted, with just mild improvements during therapy. Subjective quality of life improved significantly for all patients (P1: 28% at T0, 73% at T5. P2: 25% at T0, 71% at T5. P3: 35% at T0, 80% at T5). Conclusions: Intranasal esketamine showed a favorable efficacy and safety in these three cases of TRD in comorbidity with ASD (at six months: total remission = 66.66%, partial remission = 33.33%, inefficacy = 0%, drop-out = 0, severe adverse events = 0). Besides improvements in depressive symptoms, esketamine was associated with a constant decrease in suicidal thoughts. A case series is unfit to form statistical conclusions; preliminary data warrant further investigation in randomized controlled studies to validate the therapeutic potential of esketamine in this population. Full article

This review discusses emerging in vitro and in vivo strategies for the control of Acinetobacter baumannii, a critical multidrug-resistant pathogen; the increasing isolation of strains resistant to multiple drugs, including newly developed and last-resort antibiotics, has highlighted the urgent need to pursue adjunctive therapeutic technologies. The article aims to provide an overview of alternative control approaches beyond conventional antibiotics. Emphasis is placed on strategies based on the disruption of essential metabolic pathways, nanotechnology-based approaches such as antibiotic-coated nanoparticles, in vivo bacteriophage therapy, and drug repurposing, specifically compounds such as selective serotonin reuptake inhibitors (SSRIs), as a means of exploiting already approved pharmaceuticals. By synthesizing recent findings, this review highlights current advances in the development of innovative therapeutic strategies against A. baumannii infections. Full article

Background/Objectives: Predicting individual response to depression therapy prior to treatment initiation remains a critical clinical challenge, as the response rate to both selective serotonin reuptake inhibitors (SSRIs) and repetitive transcranial magnetic stimulation (rTMS) is approximately 50%, leaving treatment selection largely trial-based. This study presents a computer-aided decision (CAD) framework that predicts depression therapy outcomes from pre-treatment electroencephalogram (EEG) signals using advanced time-frequency representations and pretrained convolutional neural networks (CNNs). Methods: EEG signals from 30 SSRI patients and 46 rTMS patients are transformed into time-frequency images using Continuous Wavelet Transform (CWT), Variational Mode Decomposition (VMD), and their pixel-level fusion. Four pretrained CNN architectures, including ResNet-18, MobileNet-V3, EfficientNet-B0, and TinyViT-Hybrid, are fine-tuned and evaluated under both image-independent and subject-independent 6-fold cross-validation (CV). Results: Results reveal a clear therapy-specific pattern: CWT-based representations yield superior discrimination for SSRI outcome prediction, with ResNet-18 achieving 99.43% image-level accuracy, while VMD-based representations are statistically superior for rTMS outcome prediction, with ResNet-18 reaching 98.77%. Pixel-level fusion of CWT and VMD does not consistently improve performance over the best individual representation in either therapy context. Pairwise Wilcoxon signed-rank tests confirm a two-tier architectural hierarchy in which ResNet-18 and TinyViT-Hybrid significantly outperform MobileNet-V3 and EfficientNet-B0 across all conditions, while remaining statistically indistinguishable from each other. At the subject level, the framework achieves 82.50% and 83.53% accuracy for SSRI and rTMS, respectively, under strict subject-independent evaluation. Per-channel analysis reveals occipital dominance for SSRI under CWT and frontotemporal dominance for rTMS under VMD, consistent with known neurophysiological mechanisms. Conclusions: These findings demonstrate that the choice of time-frequency representation is therapy-specific and at least as important as architectural complexity, and that competitive performance can be achieved without recurrent or attention layers by combining well-designed spectral images with a simple pretrained residual network. Full article

Sphingolipids (SL) are essential structural and bioactive components of cell membranes, remarkably involved in inflammatory signaling and membrane dynamics. Dysregulation of SL metabolism contributes to pathological inflammation and cellular stress. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FXT), are known inhibitors of acid sphingomyelinase (aSMase), although their impact on macrophage SL remodeling and inflammatory responses remains unclear. Here, we investigated the modulation of FXT on SL species composition and inflammatory activation in THP-1-derived macrophages stimulated with inactivated SARS-CoV-2 particles, which is a model of viral-induced inflammation. Sphingolipidomic profiling revealed that FXT pre-treatment markedly reduced ceramide (Cer) species while increasing sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels, consistent with inhibition of the aSMase-Cer axis. These changes were accompanied by attenuation of proinflammatory components, including interleucin (IL)-6, IL-1β, and matrix metalloproteinase (MMP)-9, indicating that SL remodeling correlates with reduced macrophage activation. Despite pronounced alterations in membrane lipid composition, the quantification of extracellular vesicles (EVs) released by FXT-treated macrophages remained unchanged, however the EVs size distribution was smaller compared to non-treated cells. Altogether, our findings demonstrate that FXT reshapes SL metabolism and lipid membrane composition, thereby diminishing macrophage activation without affecting EVs biogenesis. This study emphasizes the immunometabolic role of SL on membrane reprogramming as a mechanism by which pharmacological aSMase inhibition modulates viral inflammation responses. Full article

Background/Objectives: Dialysis-induced hypotension (DIH) affects 10–30% of hemodialysis sessions and increases mortality. Sertraline may stabilize blood pressure by modulating the Bezold–Jarisch reflex. We aimed to evaluate the efficacy and safety of sertraline for preventing DIH. Methods: We searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov through December 2025. Random-effects meta-analysis was performed using standardized mean differences (SMD). Results: Nine studies (140 patients) met inclusion criteria. Sertraline significantly increased mean arterial pressure (SMD: 0.87; 95% CI: 0.52–1.22; p < 0.001), corresponding to approximately 8.5 mmHg. DIH episodes decreased by 35% (RR: 0.65; 95% CI: 0.48–0.88). Heterogeneity was moderate (I² = 42%). Among studies reporting safety data (n = 106), adverse events were mild (14%) with no serious events. No publication bias was detected (Egger’s p = 0.21). Conclusions: Sertraline significantly improves hemodynamic stability during hemodialysis with a favorable safety profile. It represents a promising option for DIH, particularly in patients with comorbid depression or contraindications to midodrine. Full article

This narrative literature review explores the clinical use of Ketamine as part of an untested hypothetical model framework for bridge therapy for acute suicidality. Long-term suicide rates continue to increase in the United States and in many other countries, creating a pressing public health challenge with a variety of treatment considerations. Existing standard-of-care SSRI therapeutics have a delay between administration and symptom relief at 2–6 weeks, leaving a so-called danger zone of about 1–3 months of risk for suicidal follow-through behaviors. Ketamine, a potent NMDA (N-methyl-D-aspartate) receptor antagonist, has recently seen widespread interest in both regulatory and clinical settings for increasing neuroplasticity and alleviating depressive symptoms. Ketamine’s mechanism-of-action through mTORC1 is much faster than SSRI’s downstream transcriptional regulation, leading to quicker relief of suicidal symptoms and the removal of the danger zone lag period. The current literature suggests that a controlled, supervised subanesthetic dose of Ketamine in a clinical setting has low risks of addiction or abuse, distinguishing therapeutic uses of Ketamine from recreational uses. While the biological efficacy of Ketamine is established, this conceptual review focuses on a possible initial hypothetical framework of a “Bridge Protocol.” We searched PubMed, Google Scholar, The Cochrane Library, and PsycINFO (January 2000–December 2025) to synthesize evidence regarding SSRI latency, acute Ketamine protocols, and post-discharge safety. We conclude that while promising, the proposed Ketamine Bridge Therapy requires rigorous longitudinal validation and sustained clinical studies before it can be safely used and experience widespread adoption. Full article

Accumulating evidence indicates that epigenetic and post-transcriptional mechanisms interact to shape stress vulnerability and the adaptive capacity of the central nervous system (CNS). This review aimed to identify molecular markers with potential prognostic value for stress-induced CNS disorders. We analyzed 93 publications (2008–2025) identified in PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library, including 80 original experimental and clinical studies, as well as 13 reviews and meta-analyses addressing epigenetic regulation, hypothalamic–pituitary–adrenal (HPA) axis function, CNS remodeling, and therapeutic or environmental modulation in stress-exposed models and clinical cohorts with stress-related disorders. Across studies, altered methylation of NR3C1, FKBP5, and BDNF, reduced hippocampal histone acetylation, and shifts in microRNA profiles (miR-16, miR-124, miR-132, miR-135a, miR-34c) were repeatedly associated with HPA axis dysregulation, limbic system remodeling, and phenotypes relevant to PTSD and depression. Evidence further suggests that at least some of these signatures show partial reversibility, with modulation reported after pharmacological interventions (e.g., SSRIs, histone deacetylase inhibitors, FKBP51 inhibitors, ketamine) and non-pharmacological approaches (e.g., physical activity, social support) in animal models and, to a lesser extent, in clinical and observational studies. We conclude that targeted modulation of specific epigenetic and post-transcriptional pathways supports the development of candidate biomarkers and may inform stratified prevention and treatment strategies for stress-induced CNS disorders, while acknowledging that further validation in large, well-characterized cohorts is required. Full article

Background: Treating depression and anxiety in adolescents can be challenging due to interindividual variability in medication response. With current trial-and-error prescribing practices, adolescents may undergo multiple medication changes over months or years before an effective and tolerated drug and dose are identified. Pharmacogenomic (PGx) testing can identify interindividual differences in drug metabolism, and evidence supporting PGx-guided prescribing in adults with mental disorders is growing. However, its impact on pediatric psychotropic prescribing remains underexplored. Methods: This is a protocol for a parallel-arm, multicentre, randomized controlled trial. Canadian adolescents aged 12–17 years who are initiating or switching a selective serotonin reuptake inhibitor (SSRI) for depression and/or an anxiety disorder under physician care are eligible. A total of 452 participants will be randomized 1:1 to PGx-guided SSRI prescribing (experimental) or SSRI prescribing based on current practice guidelines (control). Participants, caregivers, prescribing clinicians, outcome assessors, and investigators will be blinded to treatment allocation. Dual primary outcomes are symptom remission at 12 weeks, measured with the Quick Inventory of Depressive Symptomatology–Adolescent (QIDS-A17-SR) and the Screen for Child Anxiety Related Disorders (SCARED). Secondary outcomes, assessed at 4, 8, and 12 weeks, include participant- and physician-rated changes in depressive and anxiety symptoms, role functioning, health-related quality of life, health care utilization, cost-effectiveness, side-effect burden, medication burden, and adherence. Multiple testing will be addressed using the Hochberg method, and a parallel gated analysis will account for non-actionable genotypes. Secondary analysis will estimate minimal clinically important differences for symptom and role-functioning change with PGx-guided therapy. Discussion: At the time of writing, 36 participants have consented and been randomized to an intervention. This trial will evaluate whether PGx-guided prescribing improves symptom remission in adolescents treated with SSRIs. If efficacious, results should be interpreted with existing pediatric pharmacokinetic, observational, and adult trial data to inform PGx use in managing pediatric anxiety and depressive disorders. Full article

Parkinson disease (PD) and mood disorders represent two substantial global health burdens that increasingly co-occur as both conditions rise in prevalence worldwide. Diagnosing Parkinson disease in patients with pre-existing mood disorders is clinically challenging due to overlapping symptoms, medication effects, and shared neurobiological mechanisms. Apathy, psychomotor slowing, and fatigue may mimic depressive symptoms, leading to delayed recognition of early parkinsonism. Development of an underlying neurodegenerative disorder could account for some treatment-resistant symptoms or treatment failures if not recognized. Therefore, the identification of PD will change the treatment and management plan significantly. Accurate diagnosis of PD requires a detailed neurologic examination focusing on bradykinesia, rigidity, and resting tremor, supported when appropriate by dopamine transporter imaging (DaT scan) or other emerging biomarkers. Understanding the temporal relationship between psychiatric and motor features helps differentiate prodromal PD from primary mood disorders. Management of patients with both mood disorders and PD integrates dopaminergic replacement therapy for motor symptoms with individualized treatment of psychiatric comorbidities. Levodopa remains the cornerstone for motor control, while dopamine agonists, MAO-B inhibitors, and COMT inhibitors can be added as needed. For depression and anxiety, SSRIs and SNRIs are first-line choices; quetiapine or clozapine are preferred when treatment for psychosis is necessary. Intentional, thoughtful polypharmacy is frequently required. Non-pharmacologic interventions—including cognitive behavioral therapy, structured exercise, and patient–caregiver education—enhance mood, function, and quality of life. Multidisciplinary collaboration between neurology, psychiatry, and allied health professionals is essential for optimal outcomes. This review offers guidance to healthcare providers as well as other interested parties involved in patients with mood disorders who may also be developing or have PD, especially to those who may have limited access to neurologic resources. Full article

Background: The clinical presentation of temporal lobe epilepsy (TLE) and panic disorder can sometimes overlap, particularly when the seizure symptoms include paroxysmal episodes of intense fear and autonomic symptoms. As a result, patients with TLE can be misdiagnosed with a primary psychiatric illness, which leads to inappropriate treatment, worsening of the underlying condition and decreased function and quality of life. Clinical case: We present the case of a 46-year-old woman, known for a 20-year history of generalized epilepsy and major depressive disorder with panic attacks that were refractory and persistent despite trials of SSRIs, benzodiazepines and cognitive behavioral therapy (CBT). While hospitalized for video-EEG monitoring in the context of worsening epilepsy, she was found to have TLE seizures presenting as what the patient had described as panic attacks, and that sometimes progressed to secondarily generalized seizures. Following a transition from a medication regimen targeting generalized epilepsy to one more appropriate for focal seizures, the patient experienced clinical improvement with a decrease in the magnitude and frequency of panic symptoms. Conclusions: This case, in combination with other case reports in the literature, demonstrates the need for clinical suspicion of TLE in patients presenting with atypical panic-like episodes or a refractory panic disorder, especially in cases known for epilepsy or having risk factors for seizure disorder. It also highlights the importance of comprehensive diagnostic evaluation in neuropsychiatric presentations, including EEG and brain imaging, to ensure accurate diagnosis and appropriate management. Full article

Studies of adult depressed patients report that selective serotonin (5-HT) reuptake inhibitors (SSRIs) like clomipramine (CMI) have secondary effects on sperm quality. The epididymis possesses an autonomous serotonergic system critical for sperm maturation, whose establishment during neonatal development remains unexplored as a target for SSRI programming. We hypothesized that neonatal CMI exposure would disrupt the developing epididymal 5-HT system, leading to permanent sperm dysfunction. CMI (30 mg/kg s.c.) was administered to male rats between postnatal days 8–21. At 3 months, sperm from the epididymal cauda was evaluated, and 5-HT levels were measured in the testis, caput, and cauda epididymis. Our novel findings demonstrate that neonatal CMI exposure induces region-specific, long-term alterations in epididymal 5-HT levels (decreased in caput, increased in cauda) without affecting testicular 5-HT. This reprogramming of the local serotonergic milieu was associated with reduced sperm concentration, viability, normal morphology, and motility, alongside increased mitochondrial activity and reactive oxygen species. This study reveals, for the first time, that the epididymal serotonergic system is a key target for neonatal SSRI programming, providing a mechanistic link (altered 5-HT homeostasis) between early-life exposure and persistent sperm defects in adulthood. Full article