Search Results (578)

Background/Objectives: Acute pancreatitis (AP) lacks disease-modifying pharmacotherapy. Neuroimmune, serotonergic, and redox-regulated pathways may modulate inflammatory amplification and acinar injury, although pharmacovigilance data link some psychotropic drug classes to AP risk. This review synthesized controlled rodent studies evaluating neuromodulatory interventions with serotonergic, stress-axis, or ferroptosis-linked targets in experimental AP. Methods: PubMed, Scopus, eLIBRARY.ru, and Elicit were searched in January 2026, supplemented by Google Scholar audit and citation chasing. Eligible studies were controlled in vivo rodent experiments using validated AP models with quantitative outcomes. Intervention timing was classified a priori as a primary analytic variable. Risk of bias was assessed with SYRCLE. A prespecified audit showed that no subset met the criteria for quantitative pooling because of heterogeneity in model class, compounds, timing, outcome definitions, units, and sampling timepoints. Mechanism-stratified qualitative synthesis was therefore performed. The protocol was registered on OSF (doi: 10.17605/OSF.IO/CZXDJ). Results: Nine studies (1992–2023) yielded 410 outcome rows across three mechanistic strands. Serotonergic modulation (5-HT₂/5-HT₂A-focused; six studies) reduced serum amylase/lipase (−37% to −65% vs. disease controls) and histological injury, with receptor-selectivity data supporting 5-HT₂A-mediated mechanisms. Stress-axis modulation with thiadiazine L-17 reduced 7-day mortality in two severe models (from 50–70% to 30%). Olanzapine attenuated ferroptosis-linked injury via off-target antioxidant activity independent of serotonergic receptors. All interventions were prophylactic, peri-induction, or very early post-induction; no delayed therapeutic-window studies were identified. Most SYRCLE domains were unclear, particularly allocation concealment and blinding-related procedures. Conclusions: Neuromodulatory pathways modulate experimental AP in rodents, but evidentiary strength differs across mechanistic strands. Inference is constrained by absent therapeutic-window testing, heterogeneous endpoints, and reporting deficits. The findings support mechanism-level target prioritization rather than clinical repurposing. Full article

Background: Religious affiliation has traditionally served as a coping strategy during stressful events such as the COVID-19 pandemic. Pregnant women faced heightened stress during the pandemic due to concerns about their health as well as that of their fetus. This study examined the prevalence of self-reported religious affiliation among SARS-CoV-2-positive pregnant women and investigated differences in psychiatric diagnoses and pregnancy outcomes based on religious affiliation. Methods: The study included all asymptomatic or mildly symptomatic SARS-CoV-2-positive pregnant women who received care at the Mayo Health System from March 2020 through October 2021 and completed the routine religious affiliation questionnaire. Those selecting “none” were categorized as having no religious affiliation (RA−), whereas those selecting a specific religion were categorized as religiously affiliated (RA+). Results: Among 609 women, 49.6% were RA+ and 50.4% were RA−. RA+ women were more likely to be white, married, college-educated, and have fewer prior abortions. There were no significant differences in rates of depression, anxiety, psychotropic medication use, substance use, or pregnancy and labor complications between RA+ and RA− groups. Conclusions: Half of the women in this cohort reported no religious affiliation. Previously reported protective associations between religiosity and mental health were not observed when religious affiliation alone was examined. Full article

Objective: This study examined psychological resilience (PR) as a potential moderator and mediator of the association between borderline personality symptoms (BPS) and suicidal ideation (SI) among university students. Method: A cross-sectional design was used with (N = 257) university students. Moderation and mediation were tested in separate, theory-guided models using the PROCESS macro for SPSS, version 28. The moderation model (Model 1) and the mediation model (Model 4) were estimated with heteroskedasticity-consistent standard errors (HC3). In the adjusted analyses, sex, age, previous psychological consultation, previous psychotropic medication use, and family history of mental illness were entered as covariates. The indirect effect was evaluated using percentile bootstrap confidence intervals based on (5000) resamples. Results: BPS was positively correlated with SI, whereas PR was negatively correlated with both BPS and SI. In the adjusted moderation model, BPS was positively associated with SI (b = 0.118, p < 0.001) and PR was negatively associated with SI (b = −0.204, p = 0.048), but the interaction term was not significant (b = −0.001, p = 0.820) with negligible explained variance (ΔR² = 0.0003). In the adjusted mediation model, BPS was significantly associated with lower PR (a: b = −0.135, p < 0.001), and PR was associated with lower SI while controlling for BPS and the covariates (b: b = −0.216, p = 0.028). The total effect of BPS on SI was significant (c: b = 0.146, p < 0.001), and the direct effect remained significant after including PR (c′: b = 0.117, p < 0.001). The indirect effect was significant (ab = 0.029; 95% bootstrap CI [0.005, 0.061]). Conclusions: Psychological resilience did not moderate the association between BPS and suicidal ideation, but it showed a statistically significant indirect association consistent with the proposed mediation model. Higher BPS were associated with lower resilience, which in turn was associated with higher suicidal ideation. These findings suggest that resilience-related targets may complement interventions addressing core BPS-related risk processes, while the cross-sectional design precludes causal conclusions. Full article

Background: Health and social outcomes of previous opiate users (POUs) are not well-documented. We characterize the life situation, health status, and health-related quality of life (HRQoL) of POUs entering antiviral hepatitis C (HCV) treatment, compared with HCV patients without past illicit opiate use (NOU), and with HCV patients currently in opiate agonist treatment (OAT). Methods: Data are taken from the German Hepatitis C-Registry (“Deutsches Hepatitis C-Register”, DHCR), a multi-centre registry study focussing on the course and outcome of HCV treatment with directly acting antivirals. At treatment entry, patients underwent a standardized clinical assessment, including the Short Form 36 (SF-36) for self-reported HRQoL. Results: POUs (n = 734) and OAT patients (n = 554) were similar with regard to age, sex, migrant background, and psychiatric comorbidity. Employment rate and cannabis, alcohol, and smoking abstinence rates were higher for POUs than for OAT patients, but still lower than for NOU (n = 4147) patients. Mental and physical HRQoL was better for POUs than for OAT patients, but worse than for NOU patients. Compared with SF-36 normative data, POUs showed decreased HRQoL, especially regarding mental health. Conclusions: Compared with opiate-dependent patients in OAT, POUs showed less psychotropic substance use and better HRQoL. Compared with NOU patients and the general population, mental health problems were especially increased. Challenges persist for POUs even during abstinence from opiates, highlighting the need for targeted interventions tailored to the specific needs of this population. Full article

Background: Multimorbidity frequently involves overlapping neuro-psychic, cardiometabolic, and renal disturbances, yet clinical assessment often relies on diagnosis-based comorbidity counts that may not fully capture cumulative physiological stress. We developed the Neuro–Cardio–Renal Stress Index (NCR-SI) as a pragmatic composite framework to describe multisystem burden using routinely available clinical data. Methods: This cross-sectional study analyzed electronic medical record data from adult patients with chronic conditions. NCR-SI integrates three domains: neuro-psychic burden (text-derived indicators and psychotropic medication use), cardiometabolic stress (triglyceride–glucose index and cardiometabolic diagnoses), and renal function (MDRD-estimated eGFR staging). Importantly, this study is not intended to demonstrate incremental predictive value over individual components or established comorbidity indices. Rather, it presents NCR-SI as a transparent, domain-based descriptive framework and reports its internal coherence and distribution across clinically recognizable multimorbidity contexts. Results: A total of 148 patient records were screened; 143 patients met complete-case criteria and were included in the main NCR-SI analyses. NCR-SI ranged from 0 to 10 (median 5). Higher scores were observed in renometabolic profiles. NCR-SI showed expected structural associations with declining renal function (eGFR; ρ ≈ −0.71), moderately with the TyG index (ρ ≈ 0.42), and weakly with medication burden. Correlation with age-adjusted CCI was minimal (ρ ≈ 0.09), indicating limited overlap with diagnosis-based comorbidity counts. Domain-specific correlations were consistent with predefined score construction rules, particularly between the renal domain and eGFR, and between the cardiometabolic domain and TyG. Conclusions: NCR-SI provides a pragmatic, integrative descriptor of neuro-cardio-renal stress using routinely collected clinical data. Rather than replacing established comorbidity indices, NCR-SI may complement them by summarizing multidimensional physiological burden patterns. NCR-SI is proposed as a research-oriented, hypothesis-generating descriptive framework. External validation in independent cohorts and longitudinal evaluation against clinically meaningful outcomes (e.g., hospitalization, mortality, functional status, healthcare utilization) are required before any claims of clinical performance can be made. Full article

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

Background: It is well known that the university period is an important stage for young adults, involving significant academic and psychosocial adjustments. Students with greater Mental Health Literacy (MHL), which is defined as the knowledge, beliefs, and skills individuals have regarding mental health and mental illness, are better able to identify difficulties, seek help, and adopt healthier coping strategies. This study aims to describe the MHL levels of undergraduate health students and identify associated factors related to academic life, mental health and psychological state. Methods: A cross-sectional, self-administered, web-based survey was conducted using a non-probability sampling strategy among undergraduate students in health-related degrees at a Portuguese higher-education institution. Data was collected using a general characterization questionnaire and the following instruments: MHL Questionnaire, Academic Life Satisfaction, Subjective Happiness Scale, Psychological Well-Being Scale (PWBS), and Depression Anxiety Stress Scale. Bivariate and linear regression analyses were employed to identify factors associated with MHL. Results: A total of 306 students (79% female, mean age = 21.6 years; 59% nursing students) participated. The median MHL score was 70 (range: 30–80). The linear regression model explained 17.5% of the variance in MHL. Higher MHL levels were associated with having the course as a first choice, holding a previous degree, reporting taking psychotropic medication use (which may reflect previous mental health service utilization), and higher levels of psychological well-being. Conclusions: This study provides evidence on factors associated with MHL among undergraduate health students, suggesting that higher MHL is associated with greater psychological well-being, highlighting the potential importance of integrating strategies to promote MHL and psychological well-being in health and nursing education. However, these findings should be interpreted with caution due to the single-institution convenience sample, potential self-selection and reporting biases, and cross-sectional design, which limits causal inferences. Full article

The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders across six domains: perceived positive effects, adverse effects, reasons for use, route of administration, polydrug use, and dose amounts. Mood-related concerns were the primary reason for use (53%). Users reported positive effects, most often improvements in emotional well-being (65%). Adverse effects were predominantly psychological or mood-related (56%). A total of 70% of reported doses exceeded 149 mg, suggesting a trend toward higher dose use. Intravenous administration (40%) and sublingual troches (23%) were the most frequently reported routes. Concurrent use of prescribed psychotropics, cannabis, and psychedelics was also reported. This analysis identified substantial heterogeneity in individual-reported experiences. Frequent high-dose use, dose escalation, and polydrug exposure underscores the importance of clinical monitoring and attention to addiction potential and drug–drug interactions. The findings should be interpreted with caution, as follow-up and clinical verification were not possible; however, the data provide an unfiltered view of individual experiences in relation to ketamine use outside the clinical setting. Full article

Background: Decades of randomized controlled trials (RCTs) support cognitive behavioral therapy (CBT) for pediatric anxiety, but exclusion criteria may limit generalizability to routine settings. We examined common exclusion criteria in recent CBT RCTs for pediatric anxiety, trends in these criteria over time, and whether meeting RCT exclusion criteria affects outcomes in a naturalistic sample. Methods: We reviewed 81 RCTs from the past 25 years assessing CBT for pediatric anxiety or related disorders to identify common exclusion criteria. We examined how often youth seeking exposure-based treatment for anxiety or OCD at an urban community health center met these exclusion criteria and whether this impacted treatment response, using three-year retrospective chart review data (n = 94). Results: Common exclusion criteria in identified RCTs included psychotropic medication use (66.7%), autism spectrum disorder (63.0%), and other psychiatric comorbidities. Suicidal ideation increased as an exclusion criterion over time (p < 0.05, Cramér’s V = 0.23). Based on these criteria, 53% of participants in our naturalistic sample would have been excluded from one or more RCTs. Excluded patients did not differ in baseline characteristics. Excluded youth required nearly twice as many treatment sessions and had more than double the rate of case management utilization (all ps < 0.01). Conclusions: Youth who would have been excluded from at least one RCT had poorer prognoses. Findings support continued emphasis on pragmatic trials to advance understanding of how to augment treatments to better meet the diverse needs of youth. Full article

Background/Objectives: An extensive body of data suggests that inflammation may contribute to the pathophysiological mechanisms of psychiatric illness. Circumstantial evidence implied that low-dose aspirin (LDA) may enhance the therapeutic efficacy of psychotropic drugs. We examined whether LDA administration with psychotropic medications is associated with medication regimen stability and other therapeutic effects in patients with bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). Methods: This retrospective study analyzed data from Clalit Health Services’ Southern District database in Israel, including 1924 patients treated between 2017 and 2019. The Study Group consisted of patients treated with LDA plus psychotropic medications, whereas the Control Group included patients treated only with psychotropic medications. Study outcomes included suicide attempts and pharmacotherapy-related negative events, defined as psychotropic dose escalation, augmentation, or switching. Results: The study group included 137 patients (55% males, age 63.3 ± 12.3 years), and the control group included 1787 patients (60% males, age 47 ± 16.9 years). Significant differences were observed across nearly all outcomes, favoring the LDA co-treatment group. Patients in the study group exhibited lower rates of medication dosage increase (40 [29%] vs. 726 [40.5%], p = 0.01); fewer changes and/or additions of psychotropic medications (37 [26.9%] vs. 778 [43.5%], p < 0.001); and a non-significantly lower rate of suicide attempts (0 [0%] vs. 16 [0.9%], p = 0.53). Conclusions: Overall, LDA co-treatment was associated with better clinical outcomes among patients with BD, schizophrenia, and SAD. Follow-up large-scale epidemiological studies and prospective randomized clinical trials are needed to examine the therapeutic potential of add-on LDA to psychotropic medications. 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

Background: 47,XYY syndrome is a relatively common sex chromosome aneuploidy that remains largely underdiagnosed. While its somatic phenotype is often mild, growing evidence indicates a substantial burden of neurodevelopmental and psychiatric morbidity. However, the characterization of the neuropsychiatric phenotype across development, particularly during adolescence, and the associated treatment challenges remain incomplete. Objectives: To provide a comprehensive narrative review of the neuropsychiatric phenotype of 47,XYY syndrome and to illustrate clinical complexity and treatment response through a case series of adolescents. Methods: A narrative review of the literature was conducted focusing on genetics, neurodevelopmental and psychiatric features, neuroimaging and neurophysiology findings, clinical course, and management strategies in 47,XYY syndrome. This review is complemented by a case series of adolescents with confirmed 47,XYY karyotype, evaluated for developmental history, psychiatric comorbidity and response to pharmacological and non-pharmacological interventions. Results: The literature consistently describes increased risks of language impairment, executive dysfunction, ADHD, autism spectrum traits, and emotional and behavioral dysregulation in males with 47,XYY syndrome. Psychiatric vulnerability appears to increase during adolescence and adulthood, with elevated rates of mood, psychotic, and substance use disorders. The presented cases illustrate a convergent clinical trajectory marked by early developmental delays, progressive behavioral dysregulation in adolescence and limited or inconsistent response to multiple classes of psychotropic medications, suggesting a pattern of pharmacoresistance in a subset of patients. Conclusions: 47,XYY syndrome is associated with a distinct and heterogeneous neuropsychiatric phenotype that extends beyond early neurodevelopmental disorders. Early diagnosis alone may be insufficient to prevent severe psychiatric outcomes, highlighting the need for long-term monitoring and integrated, multidisciplinary management. Further research is required to identify early predictors of high-risk trajectories and to optimize treatment strategies for this population. Full article

The primary and secondary objectives of this article are, respectively, to measure the effect of habitual physical activity on total medication expenditures and on expenditures specifically related to psychotropic drugs among primary healthcare users in a large Brazilian city. This cross-sectional study with a retrospective component was conducted using Propensity Score Matching (PSM). PSM is a robust and widely utilized method in studies evaluating the impact of public policies, particularly in observational data settings where randomization is infeasible. Medication expenditures and habitual physical activity data referring to the past 12 months were collected from 250 users of both sexes, aged over 40 years, across seven primary healthcare units. The average medication expenditure was USD 6.33 (95% CI: −206.64 to −31.02), and for psychotropics, USD 0.63 (95% CI: −217.75 to −11.87). The effect of physical activity on expenditures showed that more active individuals spent on average USD 34.83 less on all medications and USD 4.34 less on psychotropics compared to less active individuals. The findings of this study reinforce the importance of the physical activity as a health promotion strategy and as a means to reduce public health expenditures. Full article

Benzodiazepines (BZDs) are globally prevalent psychotropic substances valued for their anxiolytic, hypnotic, anticonvulsant, and myorelaxant properties. Pharmacologically, they act as positive allosteric modulators of the ionotropic GABA_A receptor, enhancing inhibitory synaptic transmission. However, prolonged use poses a significant public health concern, risking adverse effects such as cognitive impairment, motor incoordination, tolerance, and physical dependence. The development of tolerance is mediated by complex neurobiological changes, notably the downregulation of GABA_A receptor subunits and a compensatory sensitization of excitatory glutamatergic systems. Effective management of established dependence requires comprehensive psychological intervention coupled with pharmacological substitution (switching to a long-acting BZD) and gradual dose tapering. Preventive measures are complex, emphasizing short-term prescriptions, minimum effective dosing, and selecting non-pharmacological or alternative pharmacological agents, such as SSRIs/SNRIs, to mitigate the risk of developing tolerance and dependence. This expert review aims to compile the most relevant, representative, and recent literature summarizing the pharmacology, clinical indications, adverse effects, misuse, and abuse of BZDs that ultimately lead to BZD use disorder (BUD). It also details the involved neurobiological mechanisms and discusses critical preventive and therapeutic strategies, providing readers with the main aspects to consider for addressing this global public health problem. Full article

Background: Major depressive disorder (MDD) is often accompanied by generalized anxiety disorder (GAD), a comorbidity linked to greater illness burden and potentially poorer outcomes. Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are established treatments for MDD, yet the impact of comorbid GAD and concomitant medications remains unclear. This study aimed to compare rTMS/iTBS treatment outcomes between patients with MDD with and without comorbid GAD, and to examine the association between concomitant psychotropic medication use, stimulation protocol, and treatment response in a real-world clinical setting. Methods: We conducted a retrospective observational analysis using registry data from 108 patients (MDD + GAD: n = 36; MDD only: n = 72). Patients received either Left-iTBS or Right-rTMS. Baseline severity, percentage change in Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAMD-17) scores, response, and remission were assessed. Logistic and linear regression models adjusted for age, sex, and baseline severity were applied. Sensitivity analyses stratified by stimulation protocol and benzodiazepine (BDZ) use were performed. Results: Baseline severity did not differ between groups. MADRS reduction was numerically lower in the comorbid GAD group (48.3% vs. 52.7%, p = 0.09), whereas HAMD-17 reduction was comparable. Response and remission rates did not differ significantly. Medication use and stimulation protocol did not show statistically significant independent associations with outcomes. Sensitivity analyses confirmed equivalent outcomes between Left-iTBS and Right-rTMS. BDZ users showed a non-significant trend toward lower MADRS improvement and remission. Conclusions: rTMS/iTBS produced substantial clinical improvement and was well tolerated in both patients with MDD and those with MDD comorbid with GAD. Although comorbid anxiety showed a modest tendency to attenuate MADRS score reduction, overall response and remission rates were comparable between groups. Neither concomitant medications nor stimulation protocol significantly affected treatment outcomes, while the potential influence of BDZ exposure warrants further investigation. Full article