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Search Results (221)

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Keywords = selective serotonin reuptake inhibitors (SSRIs)

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9 pages, 1004 KB  
Article
Serotonergic Antidepressant Use Is Not Associated with Increased Revision but Alters Postoperative Pain Following Rotator Cuff Repair
by Ronak J. Mahatme, Shawn A. Moore, Anish Gangavaram, Esha Reddy, David L. Bernholt and Brian M. Grawe
Psychoactives 2026, 5(3), 21; https://doi.org/10.3390/psychoactives5030021 - 5 Aug 2026
Viewed by 130
Abstract
Rotator cuff tears are common, and although surgical repair is frequently performed, re-tear and complication rates remain substantial. The impact of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) on postoperative outcomes after rotator cuff repair is not well understood. Using [...] Read more.
Rotator cuff tears are common, and although surgical repair is frequently performed, re-tear and complication rates remain substantial. The impact of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) on postoperative outcomes after rotator cuff repair is not well understood. Using the TriNetX Research Network, adult patients undergoing arthroscopic rotator cuff repair were identified and stratified into SSRI/SNRI users (at least one prescription within 3 months preoperatively and continued use within 2 years postoperatively) and non-users. Propensity score matching was performed for demographic and medical comorbidities, yielding 2457 patients in each cohort. At 1-year follow-up, SSRI/SNRI users demonstrated lower rates of adhesive capsulitis compared with controls (3.1% vs. 5.8%; RR 0.53; 95% CI 0.41–0.70; p < 0.001), with similar revision rotator cuff repair rates. This pattern persisted at 2 years (3.6% vs. 6.1%; RR 0.58; 95% CI 0.45–0.75; p < 0.001), with comparable revision rates between groups. There were no differences in 30-day emergency department visits, readmissions, or 90-day postoperative infections. SSRI/SNRI users had lower early opioid use (21.0% vs. 29.5%; RR 0.71; p < 0.001) but higher prolonged (17.2% vs. 14.1%; RR 1.22; p = 0.003) and chronic opioid use (16.7% vs. 9.1%; RR 1.84; p < 0.001). In this large national cohort, SSRI/SNRI use was associated with lower rates of adhesive capsulitis and differences in postoperative opioid utilization, without differences in revision rotator cuff repair or short-term complications. These findings reflect associations rather than causation and highlight the need for further studies to clarify underlying mechanisms and clinical implications. Full article
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17 pages, 1597 KB  
Article
Antidepressants and Road Safety: A Forensic Toxicological Perspective Based on Observational Data and Current Evidence
by Davide Filardi, Francesca Vernich, Federico Mineo, Giulio Mannocchi and Roberta Tittarelli
Pharmaceuticals 2026, 19(7), 1118; https://doi.org/10.3390/ph19071118 - 20 Jul 2026
Viewed by 375
Abstract
Background/Objectives: Antidepressants are widely prescribed medications that may affect psychomotor performance and driving ability depending on their pharmacological profile. This study investigated the prevalence and patterns of antidepressant use among drivers undergoing forensic toxicological evaluation and explored their potential implications for road safety. [...] Read more.
Background/Objectives: Antidepressants are widely prescribed medications that may affect psychomotor performance and driving ability depending on their pharmacological profile. This study investigated the prevalence and patterns of antidepressant use among drivers undergoing forensic toxicological evaluation and explored their potential implications for road safety. Methods: An observational study was conducted on n = 6316 drivers undergoing forensic toxicological assessment following licence suspension for driving under the influence (DUI) of alcohol and/or drugs between January 2023 and December 2025. Reported antidepressants were classified into selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), tricyclic antidepressants (TCAs), norepinephrine–dopamine reuptake inhibitors (NDRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), and monoamine oxidase inhibitors (MAOIs). Distribution patterns were analysed descriptively and discussed considering the available literature. Results: Antidepressant use was reported by n = 132 participants (2.1%). SSRIs were the most common class (44.0%), followed by SNRIs (26.5%) and SARIs (17.4%). TCAs (6.1%), NDRIs (3.7%), and NaSSAs (2.3%) were less common, while no MAOI use was reported. Among antidepressant users, n = 28 individuals (21.2%) tested positive for other psychoactive substances, including benzodiazepines, cocaine, and cannabinoids. Conclusions: The use of antidepressants was relatively uncommon in the study population. However, clinical evaluation remains important, particularly at the start of treatment and during dose adjustments to determine the potential for an increased risk while driving. Further studies integrating toxicological analyses and clinical data are needed to better define the relationship between antidepressant exposure, polysubstance use, and road safety. Full article
(This article belongs to the Special Issue Effects of Drug Abuse and Its Consequences on Health)
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16 pages, 741 KB  
Review
Hyponatraemia in Neck of Femur Fracture: A Narrative Review of Epidemiology, Pathophysiology, and Outcomes
by Amirmohammad Heidari, Kiana Heidary, Hussain Aladdin Leelo and Mohamed H. Ahmed
Geriatrics 2026, 11(4), 85; https://doi.org/10.3390/geriatrics11040085 - 13 Jul 2026
Viewed by 479
Abstract
Background: Hyponatraemia is the commonest electrolyte disturbance encountered in older adults admitted with neck of femur (NOF) fracture. It is now recognised both as associated with fragility fracture and as an independent prognostic indicator for adverse post-operative outcomes. Methods: Narrative review of the [...] Read more.
Background: Hyponatraemia is the commonest electrolyte disturbance encountered in older adults admitted with neck of femur (NOF) fracture. It is now recognised both as associated with fragility fracture and as an independent prognostic indicator for adverse post-operative outcomes. Methods: Narrative review of the literature, with emphasis on cohort studies, meta-analyses and mechanistic investigations pertinent to hip fracture in adults. Results: Admission hyponatraemia affects approximately 13–20% of NOF patients, twice the prevalence observed in age-matched community-dwelling elders and broadly comparable to general geriatric inpatients. A further 20–30% develop in-hospital, predominantly post-operative, hyponatraemia. Mild hyponatraemia (130–135 mmol/L) accounts for 75–85% of cases. Pathophysiology is multifactorial: hypovolaemia from the fracture haematoma, fasting and pre-admission “long lie”; drug effects (thiazides, selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors, carbamazepine, opioids); and non-osmotic arginine vasopressin (AVP) release driven by pain, nausea and peri-operative stress. Chronic hyponatraemia is hypothesised to contribute to fracture risk through three convergent mechanisms, direct sodium-dependent stimulation of osteoclastogenesis with AVP-mediated bone resorption, subtle cerebral dysfunction producing gait and attention deficits, and sarcopenia, although much of this mechanistic evidence derives from animal and in vitro studies rather than from patients with hip fracture. Hyponatraemia is reproducibly associated with longer length of stay, delayed surgery, and an adjusted 30-day mortality hazard of approximately 1.15–1.40. A dose–response relationship with severity is demonstrable; pre-operative correction has not been shown to improve outcomes in any randomised trial. Conclusions: Hyponatraemia in NOF fracture is consistently a consequence of the acute event and, at minimum, a robust marker of frailty and adverse prognosis. Whether it also causally contributes to fracture risk remains unproven, since the supporting human evidence is entirely observational and mechanistic, each contributing study carries methodological weaknesses that warrant caution, and no interventional study has established causality. Where hyponatraemia is mild and isolated, current evidence does not support delaying surgery; moderate and severe hyponatraemia warrant individualised assessment, with cautious correction proceeding alongside surgical planning rather than postponing it. Given the absence of interventional evidence, no correction strategy can yet be recommended to improve fracture or surgical outcomes. Prospective trials of targeted correction strategies and rehabilitation outcomes are overdue. Full article
(This article belongs to the Special Issue Comprehensive Geriatric Assessment of Older Surgical Patients)
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22 pages, 1608 KB  
Article
Study on the Gut–Brain Mechanism of Escitalopram for Alleviating Symptoms of Disorders of Gut–Brain Interaction in the Elderly—A Cohort Study
by Qiao Tang and Jing Li
J. Clin. Med. 2026, 15(13), 5100; https://doi.org/10.3390/jcm15135100 - 30 Jun 2026
Viewed by 619
Abstract
Objective: Disorders of gut–brain interaction (DGBIs) are characterized by functional impairments without identifiable organic causes, with their prevalence increasing with age. Emerging evidence suggests that selective serotonin reuptake inhibitors (SSRIs), such as escitalopram oxalate, may influence DGBIs through the brain–gut axis, though the [...] Read more.
Objective: Disorders of gut–brain interaction (DGBIs) are characterized by functional impairments without identifiable organic causes, with their prevalence increasing with age. Emerging evidence suggests that selective serotonin reuptake inhibitors (SSRIs), such as escitalopram oxalate, may influence DGBIs through the brain–gut axis, though the precise mechanisms driving their therapeutic effects remain unclear. This study investigated the impact of escitalopram oxalate on elderly patients with DGBIs in an outpatient department to elucidate these mechanisms. Methods: This study was an observational cohort study. We recruited elderly patients diagnosed with DGBIs. Patients receiving standard treatment alone were assigned to the control group, while patients receiving standard treatment plus 10 mg of escitalopram oxalate daily were assigned to the exposure group. Emotional and gastrointestinal symptoms were assessed at baseline and after 12 weeks of treatment using validated symptom scales. Additionally, stool samples were collected at both time points and analyzed via 16S amplicon sequencing to evaluate the changes in gut microbiota. Results: A total of 83 elderly patients with DGBIs were included in the study, comprising 40 patients in the control group and 43 in the exposure group. After 12 weeks, the exposure group showed significantly greater reductions in their scores on the Gastrointestinal Symptom Rating Scale (GSRS), Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ), Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) compared with the control group (e.g., GSRS: 17.00 ± 0.85 vs. 22.58 ± 3.18, p < 0.001; p < 0.01 for all other scale comparisons), with higher effective and recovery rates. Notably, the exposure group showed significant alterations in the abundance of four genus-level taxa (Blautia, Butyricicoccus, Prevotellaceae UCG-003, and Streptococcus) and two species-level taxa (Eubacterium-hallii-group and Parabacteroides-merdae). Conclusions: The escitalopram oxalate treatment was associated with significant improvements in both emotional and gastrointestinal symptoms in elderly patients with DGBIs. These improvements may be linked to alterations in specific gut microbiota taxa, offering a preliminary hypothesis for further investigating the underlying mechanisms of the gut–brain axis. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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21 pages, 2554 KB  
Review
Prevention of Gastrointestinal Bleeding in Patients Receiving Direct Oral Anticoagulants: A Narrative Review and Practical Framework for Prescribers
by Nicoleta Dubei, Larisa Anghel, Laura-Cătălina Benchea, Radu Andy Sascău, Cristina Prisacariu, Mircea Ovanez Balasanian, Bogdan-Sorin Tudurachi, Bianca-Ștefania Profire and Cristian Stătescu
Clin. Pract. 2026, 16(7), 120; https://doi.org/10.3390/clinpract16070120 - 26 Jun 2026
Viewed by 647
Abstract
Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. [...] Read more.
Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended. Full article
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20 pages, 624 KB  
Review
Pharmacological Intensification Strategies in Highly Refractory Obsessive–Compulsive Disorder: Evidence Synthesis and a Tertiary-Care Case Series
by Mario Pinzi, Alessandro Cuomo, Pietro Carmellini, Claudia Libri, Maria B. Rescalli, Caterina Pierini, Alessia Santangelo, Benjamin Patrizio and Andrea Fagiolini
J. Clin. Med. 2026, 15(12), 4796; https://doi.org/10.3390/jcm15124796 - 20 Jun 2026
Viewed by 422
Abstract
Background: Treatment-resistant obsessive–compulsive disorder (TR-OCD) remains a major therapeutic challenge. Although current guidelines recommend optimized serotonin reuptake inhibitor (SRI) therapy, clomipramine switching, exposure and response prevention, and antipsychotic augmentation, a substantial proportion of patients continue to experience severe and disabling symptoms. In such [...] Read more.
Background: Treatment-resistant obsessive–compulsive disorder (TR-OCD) remains a major therapeutic challenge. Although current guidelines recommend optimized serotonin reuptake inhibitor (SRI) therapy, clomipramine switching, exposure and response prevention, and antipsychotic augmentation, a substantial proportion of patients continue to experience severe and disabling symptoms. In such cases, clinicians may consider pharmacological intensification strategies beyond guideline-endorsed algorithms. Methods: This study combines a structured narrative synthesis of pharmacological strategies for TR-OCD with a retrospective observational case series from a tertiary OCD referral clinic. Treatment resistance was defined as failure to achieve at least a 35% reduction in Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score after at least two adequate SRI trials, including clomipramine, and optimized exposure and response prevention when available. Five patients treated with pharmacological intensification strategies were included. The primary outcome was percentage change in Y-BOCS score at 12 weeks. Results: The case series illustrates five strategies used in highly refractory OCD: supratherapeutic SSRI dosing, SSRI plus mirtazapine augmentation, dual SSRI therapy, serotonergic intensification in a clozapine-treated patient, and glutamatergic/GABAergic augmentation with topiramate. Baseline Y-BOCS scores ranged from 28 to 32. At 12 weeks, symptom reduction ranged from 23% to 36%. One patient met criteria for response, three showed near-response, and one demonstrated partial improvement. No cases of serotonin toxicity or clinically significant cardiac complications occurred. Conclusions: These cases suggest that carefully monitored pharmacological intensification may be feasible in selected specialist settings, but efficacy and safety require confirmation in prospective controlled studies. Recommendations: Pharmacological intensification should be reserved for highly refractory patients managed in specialist services, implemented with gradual titration, structured serotonin toxicity and electrocardiographic monitoring, and explicit individualized risk–benefit discussion; dual SSRI therapy should be regarded as the most experimental and highest-risk serotonergic option; and prospective controlled studies incorporating standardized functional outcomes are needed to refine patient-selection criteria and clarify which patients may benefit. Full article
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20 pages, 2987 KB  
Review
The Potential Use of Selective Serotonin Reuptake Inhibitor Therapy for Gambling Disorders Associated with Impulse-Control Disorders
by Riccardo Gennari, Nicole Capretti, Danial Daroui, Sergio Terracina, Lorenzo Martellone, Andrea Mastrostefano and Giuseppe Greco
Targets 2026, 4(2), 19; https://doi.org/10.3390/targets4020019 - 1 Jun 2026
Viewed by 1132
Abstract
Gambling disorder (GD) constitutes a worldwide social and economic burden and is associated with impaired functioning and reduced quality of life. GD shares important mechanistic substrates with obsessive–compulsive disorder (OCD), including dysfunction of cortico-striato-thalamo-cortical circuitry and dysregulation of serotonergic pathways involved in impulsivity, [...] Read more.
Gambling disorder (GD) constitutes a worldwide social and economic burden and is associated with impaired functioning and reduced quality of life. GD shares important mechanistic substrates with obsessive–compulsive disorder (OCD), including dysfunction of cortico-striato-thalamo-cortical circuitry and dysregulation of serotonergic pathways involved in impulsivity, compulsivity, and impaired inhibitory control. On this basis, selective serotonin reuptake inhibitors (SSRIs), widely used in several psychiatric disorders, have been investigated as potential pharmacological treatments for GD. Evidence concerning fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram is heterogeneous and overall limited. Some early single-blind, randomized, and open-label studies have reported reductions in gambling urges, severity, and compulsive symptoms. However, larger and more rigorous placebo-controlled trials have frequently failed to demonstrate consistent superiority over placebo. Interpretation of these findings is further limited by small sample sizes, short observation periods, high dropout rates, heterogeneous outcome measures, and substantial placebo response. While SSRIs remain biologically plausible candidates for modulating the compulsive and impulsive dimensions of GD, current evidence does not support their routine use as first-line pharmacological treatment. Their role appears most justified in the presence of psychiatric comorbidity or within individualized, phenotype-oriented treatment strategies. Full article
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26 pages, 377 KB  
Review
Mental Health in Cystic Fibrosis in the Modulator Era: Epidemiology, Prognostic Significance, and Therapeutic Implications
by Maryam M. Almulhem and Rayan A. Siraj
J. Clin. Med. 2026, 15(10), 3953; https://doi.org/10.3390/jcm15103953 - 20 May 2026
Viewed by 692
Abstract
Individuals with cystic fibrosis (CF) face significant treatment burdens, and as life expectancy has increased, there is growing emphasis on their psychosocial well-being. Prevalence data indicate that approximately one-quarter to one-third of individuals with CF and their caregivers experience clinically significant anxiety or [...] Read more.
Individuals with cystic fibrosis (CF) face significant treatment burdens, and as life expectancy has increased, there is growing emphasis on their psychosocial well-being. Prevalence data indicate that approximately one-quarter to one-third of individuals with CF and their caregivers experience clinically significant anxiety or depression. Specifically, pooled global estimates report an anxiety prevalence of 24.9% (95% CI: 20.8–28.9%) and depression prevalence of 13–33% in adults with CF, with caregivers experiencing even higher rates (anxiety: 35–38%; depression: 20–35%). Depression is independently associated with a nearly twofold increase in mortality risk and substantially higher healthcare costs, underscoring its prognostic significance. These mental health comorbidities are consistently associated with reduced treatment adherence, diminished quality of life, increased healthcare utilisation, and decreased survival. Accordingly, psychological well-being has emerged as a key patient outcome that directly shapes engagement with care and the effectiveness of long-term CF management. International CF guidelines now recommend routine mental health screening within multidisciplinary care frameworks. Evidence-based interventions include cognitive–behavioural therapy (CBT), which is endorsed as a primary treatment, although access remains limited, and stepped-care pharmacotherapy, primarily selective serotonin reuptake inhibitors (SSRIs), for moderate to severe symptoms. Telemedicine and other digital health approaches have expanded access to psychological support, with remote CBT and online programmes demonstrating feasibility and symptom improvement during the COVID-19 pandemic and beyond. The advent of CFTR modulator therapies has significantly altered clinical outcomes, enabling many patients to achieve improved lung function and daily functioning. Nevertheless, mental health challenges persist, as individuals navigate new identity shifts and anxieties despite enhanced physical health. The implementation of mental healthcare remains inconsistent; while screening rates have increased, timely follow-up and integrated psychosocial support are frequently insufficient across care centres. This narrative review highlights the ongoing need to integrate mental health management into CF care to optimise adherence, patient outcomes, and long-term survival in the current therapeutic landscape. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Management Strategies and Patient Outcomes)
9 pages, 205 KB  
Article
Prenatal Selective Serotonin Reuptake Inhibitor Exposure and Its Impact on Neonatal Gastrointestinal and Urinary System: A Retrospective Matched Cohort Study
by Ronella Marom, Laurence Mangel, Addy S. BrandStetter, Jacky Herzlich, Dror Mandel and Yuval Bar-Yosef
Children 2026, 13(5), 630; https://doi.org/10.3390/children13050630 - 30 Apr 2026
Viewed by 370
Abstract
Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal [...] Read more.
Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal SSRI use during pregnancy and time to first stool and time to first void in healthy neonates. Methods: In this retrospective matched cohort study, neonates exposed to SSRIs in utero were matched 1:1 with unexposed controls by gestational age (GA) and weight-for-gestational-age category. The primary outcomes were time to first void and time to first stool. Multivariable linear regression was performed using log10-transformed time to first stool, adjusting for maternal age, GA, and neonatal sex. Sensitivity analyses included size-for-gestational-age and time to first feeding. Results: A total of 266 neonates were included (133 SSRI-exposed, 133 unexposed). Time to first stool was shorter in SSRI-exposed neonates compared with unexposed neonates (median 7.4 vs. 8.6 h, p = 0.023), while the time to first void did not differ. In adjusted analysis, SSRI exposure remained associated with shorter time to first stool (β = −0.08, 95% CI −0.16 to −0.001, p = 0.035), corresponding to an approximate 17% reduction. The association was consistent across sensitivity analyses. Meconium-stained amniotic fluid was associated with shorter time to first stool among SSRI-exposed neonates but not in unexposed neonates. The overall model explained a limited proportion of variance. Conclusions Prenatal SSRI exposure was associated with modest but consistent reduction in time to first stool, without affecting time to first void. While the clinical significance remains uncertain, these findings suggest a potential influence of in utero SSRI exposure on early neonatal gastrointestinal adaptation, which may be influenced by intrapartum conditions. Full article
(This article belongs to the Section Pediatric Drugs)
11 pages, 219 KB  
Article
Impact of Levothyroxine Treatment for Hypothyroidism on the Risk of Psychiatric Interventions in Children and Adolescents with Anxiety Disorders: A Retrospective Analysis of Data from the TriNetX Platform
by Marta Hilmon, Janina Kulińska, Dominik Krzyżanowski and Katarzyna Skórkowska-Telichowska
J. Clin. Med. 2026, 15(8), 2893; https://doi.org/10.3390/jcm15082893 - 10 Apr 2026
Viewed by 721
Abstract
Background/Objectives: Hypothyroidism, including subclinical hypothyroidism, may affect mental health in children and adolescents through disturbances of neurotransmission and dysregulation of the hypothalamic–pituitary–thyroid and stress axes. Anxiety disorders are common in this population and frequently coexist with somatic symptoms overlapping those of hypothyroidism, [...] Read more.
Background/Objectives: Hypothyroidism, including subclinical hypothyroidism, may affect mental health in children and adolescents through disturbances of neurotransmission and dysregulation of the hypothalamic–pituitary–thyroid and stress axes. Anxiety disorders are common in this population and frequently coexist with somatic symptoms overlapping those of hypothyroidism, complicating diagnosis and treatment. This study aimed to evaluate the association between levothyroxine treatment for hypothyroidism and the need for psychiatric interventions in children and adolescents with anxiety disorders. Methods: A retrospective cohort study was performed using data from the TriNetX global research network. Patients aged 5–18 years with diagnoses of hypothyroidism (ICD-10: E03) and anxiety disorders (ICD-10: F41) were included. Two propensity score–matched cohorts were analysed: patients treated with levothyroxine (n = 1861) and untreated patients (n = 1861). Outcomes included psychiatric hospitalisations, use of selective serotonin reuptake inhibitors and tricyclic-like antidepressants, frequency of psychiatric and psychotherapeutic consultations, and the occurrence of suicidal ideation and self-harm. Results: Levothyroxine treatment was associated with lower odds of SSRI use (OR = 0.58; p < 0.001), fewer psychiatric consultations (OR = 0.48; p < 0.001), and lower recorded use of psychotherapy (OR = 0.75; p = 0.029). Suicidal ideation and self-harm were recorded less frequently in the treated group (OR = 0.53; p = 0.001). No significant differences were observed in psychiatric hospitalisation rates. Use of tricyclic-like antidepressants was uncommon and did not differ significantly between groups. Conclusions: Among children and adolescents with comorbid anxiety disorders, levothyroxine treatment for hypothyroidism is associated with lower recorded utilization of certain psychiatric services and lower recorded rates of suicidal ideation and self-harm. Due to the retrospective design, causal inferences cannot be made, and the findings should be considered hypothesis-generating, requiring confirmation in prospective studies with standardised psychiatric outcome measures. Full article
(This article belongs to the Section Mental Health)
13 pages, 625 KB  
Systematic Review
Sex Differences in Psychotropic Drug Exposure and Safety: A Systematic Review Toward Personalized Dosing Strategies
by Maria Puntarello, Giuseppe Davide Albano, Stefania Zerbo, Ginevra Malta and Antonina Argo
J. Pers. Med. 2026, 16(4), 189; https://doi.org/10.3390/jpm16040189 - 31 Mar 2026
Cited by 1 | Viewed by 1026
Abstract
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 [...] Read more.
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
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16 pages, 725 KB  
Review
A Narrative Review of Augmentation Strategies in Obsessive-Compulsive Disorder: Antipsychotics as Mainstay and Emerging Role of Extended-Release Methylphenidate
by Julija Grigaitytė and Robertas Strumila
Pharmaceuticals 2026, 19(4), 551; https://doi.org/10.3390/ph19040551 - 30 Mar 2026
Viewed by 3150
Abstract
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 [...] Read more.
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
(This article belongs to the Section Medicinal Chemistry)
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15 pages, 896 KB  
Case Report
Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression with Comorbid Autism Spectrum Disorder: Three Case Reports
by Alessandro Guffanti, Matteo Leonardi, Natascia Brondino, Bernardo Dell’Osso, Vassilis Martiadis and Miriam Olivola
Clin. Pract. 2026, 16(3), 61; https://doi.org/10.3390/clinpract16030061 - 13 Mar 2026
Viewed by 1410
Abstract
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 [...] Read more.
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
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23 pages, 1106 KB  
Review
Revisiting the Fight Against Acinetobacter baumannii: Emerging Non-Antibiotic Strategies
by Victor Hugo Montini, Laura Santana Buso, Pedro Henrique Takata, Gabriel Henrique Maximino Santos, Bruna Carolina Gonçalves, Thiago Hideo Endo, Mariana Homem de Mello Santos, Eliana Carolina Vespero, Renata Katsuko Takayama Kobayashi and Gerson Nakazato
Antibiotics 2026, 15(3), 281; https://doi.org/10.3390/antibiotics15030281 - 10 Mar 2026
Cited by 2 | Viewed by 1780
Abstract
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 [...] Read more.
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
(This article belongs to the Topic Antimicrobial Agents and Nanomaterials—2nd Edition)
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41 pages, 7209 KB  
Article
Towards the Development of a Deep Learning Framework Using Adaptive and Non-Adaptive Time-Frequency Features for EEG-Based Depression Therapy Prediction
by Hesam Akbari, Sara Bagherzadeh, Javid Farhadi Sedehi, Rab Nawaz, Reza Rostami, Reza Kazemi, Sadiq Muhammad, Haihua Chen and Mutlu Mete
Brain Sci. 2026, 16(3), 301; https://doi.org/10.3390/brainsci16030301 - 9 Mar 2026
Viewed by 1139
Abstract
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 [...] Read more.
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
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