Search Results (203)

Atypical antipsychotics (AAPs) remain the most effective treatment to control irritability associated with autism spectrum disorder (ASD). Although there is no pharmaceutical treatment to target the core symptoms of ASD, AAPs reduce their severity. However, AAPs have been reported to be associated with severe adverse drug reactions (ADRs) that may lead to long-term conditions such as diabetes mellitus and heart disease. Their prevalence varies depending on the type of AAP prescribed, age, ethnicity, gender, healthcare systems, and the severity of the ASD. Current ADR monitoring guidelines exist, but they are broad in scope and do not fully account for these factors. Therefore, the need to develop ADR monitoring guidelines considering these factors has increased with the expanded use of AAPs in paediatrics with ASD. This gap in knowledge and clinical practice highlights the ongoing need for research to explore these factors and how they can inform the creation of tailored guidelines for monitoring ADRs in this population. Full article

Copay accumulator (CA) and copay maximizer (CM) programs in the United States, which prevent manufacturer copay assistance from counting toward deductibles or out-of-pocket (OOP) maximums, are increasingly used, raising concerns about costs and outcomes for patients with major depressive disorder (MDD) or bipolar disorder (BPD) treated with branded atypical antipsychotics (AAPs) and/or antidepressants (ADs). This retrospective claims study used Kythera commercial data (2020–2024) in the United States to identify adults with MDD or BPD who had at least 1 diagnosis and one branded AAP or AD prescription between 2021 and 2023, requiring 12 months’ continuous enrollment pre- (2020–2021) and post-index (2023–2024) and at least three months of post-index branded medication use. This retrospective claims study used Kythera commercial data (2020–2024) to identify adults with MDD or BPD who had at least one diagnosis and one branded AAP or AD prescription between 2021 and 2023, requiring 12 months’ continuous enrollment pre- and post-index and at least 3 months of post-index branded medication use. Patients were stratified into CA, CM, or standard copay plan (SCP) cohorts, and propensity score matching was used to compare treatment patterns and costs. Both CA and CM groups had significantly higher median OOP costs than SCPs (e.g., $75/$60 vs. $16 for MDD+AAP; p < 0.0001), and higher pharmacy costs among adherent patients. CA patients had poorer adherence and persistence, shorter treatment duration, and higher discontinuation and abandonment rates than SCPs. These findings highlight higher OOP burden and adherence challenges with CA and CM programs, underscoring the need for careful benefit design for US mental health patients. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in social and communication skills and restricted interests. It is associated with behavioural symptoms and/or comorbidities (e.g., attention deficit hyperactivity disorder (ADHD)). Developing effective treatments for ASD remains a challenge because its pathophysiology is not fully understood. Multiple treatment options are used for ASD with varying levels of effectiveness and safety profiles. Atypical antipsychotics (AAPs), particularly risperidone and aripiprazole, provide superiority over other drug classes of pharmacological interventions. However, they are linked to adverse drug reactions (ADRs), specifically metabolic and endocrine ADRs. These ADRs may lead to chronic diseases such as diabetes and cardiovascular conditions, adding strain to healthcare systems beyond the original treatment of ASD. This narrative review enhances our understanding of ASD and highlights a gap in current knowledge about the evaluation of the effectiveness and safety of pharmacological treatments, especially AAPs for ASD in paediatric patients. Full article

Atypical antipsychotics (AAP), including clozapine (Clo), aripiprazole (Ari), and risperidone (Ris), are widely used in psychiatry but can lead to kidney damage due to oxidative stress. This study investigated whether dietary supplementation with selected antioxidants—ellagic acid, vitamin C, zinc, and seleno-methionine (SeMet) in fish oil, formulated as the composite product “ProCloSupp” (PCS)—can mitigate the oxidative damage induced by subchronic administration of AAP. Rats were treated with each antipsychotic for 28 days, with PCS added in the last 14 days. The kidney tissue was examined histologically and by determining the activities of antioxidant enzymes (copper, zinc and manganese superoxide dismutase—CuZn SOD and Mn SOD, catalase—CAT, glutathione peroxidase—GPx, glutathione reductase—GR, glutathione S-transferase—GST). All AAPs caused discrete to moderate renal damage and significant changes in enzyme profiles, which were most pronounced with Ari. Clo and Ari significantly decreased CuZn SOD and Mn SOD activity, while Ris only affected Mn SOD. Clo additionally increased CAT activity, while Ari increased GPx activity. Antioxidant-related protein levels increased only in the Ris group. PCS supplementation increased CuZn SOD and GPx activities and was associated with less pronounced histopathological changes than antipsychotic treatment alone. In conclusion, subchronic Clo, Ari, and Ris exposure induces oxidative renal damage in rats, while PCS supplementation enhances antioxidant defences and attenuates tissue damage. These results support PCS as a potential nephroprotective strategy in antipsychotic therapy. Full article

Oxidative stress observed in schizophrenia and other psychiatric disorders can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. The aim of this study was to estimate in vitro the possible antioxidant properties of curcumin, the natural polyphenolic antioxidant, and its protective effects against lipid peroxidation induced by the atypical antipsychotic Ziprasidone. Curcumin (5 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL) was added to human plasma and incubated for 1 and 24 h, alone and in the presence of Ziprasidone (40 ng/mL, 139 ng/mL, 250 ng/mL). Control plasma samples were incubated for 1 and 24 h. The concentration of thiobarbituric acid-reactive substances (TBARSs; lipid peroxidation marker) was determined by the spectrophotometric method according to Rice-Evans. Curcumin at the tested concentrations significantly inhibited lipid peroxidation in human plasma by about 60%. Ziprasidone (40 ng/mL, 139 ng/mL, 250 ng/mL) significantly increased TBARS levels, but in the presence of the studied curcumin concentrations, its pro-oxidative effects were reduced by about 56%. Our results confirm that Ziprasidone in vitro may induce lipid peroxidation in human plasma, whereas curcumin protects against lipid peroxidation in human plasma caused by the antipsychotic Ziprasidone. Full article

Background/Objectives: The objective of this study is to investigate the patterns and characteristics of medication errors (MEs) associated with antipsychotic medication use in hospitals affiliated with the Ministry of Health (MOH) in Saudi Arabia and to identify areas for improvement. Methods: A retrospective descriptive analysis of MEs associated with antipsychotic use was conducted using data collected from MOH-affiliated hospitals between April 2020 and September 2022. The data were analyzed descriptively to identify the factors underpinning unsafe antipsychotic use. Results: The sample period produced 35,077 reported MEs. Reports from the Western region contributed the highest error percentage, and MEs were reported more frequently in male (76.1%, n = 26,705) and adult (97.7%, n = 34,275) patients. Pharmacists reported MEs more often than other healthcare professionals (66.5%, n = 23,312). Most MEs (89.9%, n = 31,524) originated in the prescribing stage, with missing prescription information being the most frequently reported ME type (40.5%, n = 14,206). Atypical antipsychotics accounted for the greatest proportion of reports (79.3%, n = 27,811) compared to typical antipsychotics (20.7%, n = 7262). Most ME outcomes fell into Category B: The error occurred but did not reach the patient (56.4%, n = 19,794). Factors related to staffing or workflow accounted for 21.3% (n = 7467) of the reported errors, followed by a lack of policies in relation to antipsychotics prescribing and monitoring (20.5%; n = 7195). Conclusions: MEs in hospitals in Saudi Arabia frequently involve antipsychotic medications. This study identified important targets that may help reduce such risks in the future. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) of antipsychotic medications plays an important role in optimizing treatment efficacy, reducing adverse effects, and supporting adherence. While Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS) has long been the gold standard for antipsychotic quantification, recent advances in automated platforms and microsampling raise questions about its current clinical practicality. This systematic review evaluated the clinical applicability and analytical performance of UHPLC-based methods for monitoring antipsychotic drugs, focusing on precision, recovery, matrix effects, and suitability across various biological matrices. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between 2013 and 2024 involving UHPLC-based quantification of antipsychotics in clinical samples from adult patients. Data on analytical parameters, sample matrices, and study characteristics were extracted. A custom quality checklist was used to assess methodological rigor. In addition to qualitative synthesis, non-traditional quantitative approaches were applied, including descriptive aggregation of recovery, matrix effects, and precision across studies, as well as correlation analyses to explore relationships among performance parameters. Results: Twelve studies were included, spanning a range of typical and atypical antipsychotics and metabolites. Plasma and serum demonstrated the highest analytical reliability (recovery >90%, minimal matrix effects), while dried blood spots (DBSs), whole blood, and oral fluid showed greater variability. Clinically, UHPLC–MS/MS enabled more accurate dose adjustments and identification of non-adherence, outperforming immunoassays in sensitivity, specificity, and metabolite detection. Microsampling methods showed promise for outpatient and decentralized care but require further clinical validation. Conclusions: UHPLC–MS/MS remains the most robust and reliable method for TDM of antipsychotics, especially when quantification of active metabolites is required. While logistical barriers remain, technological advances may enhance feasibility and support broader integration into routine psychiatric care. Full article

Objective: Schizophrenia is a chronic psychiatric disorder associated with increased oxidative stress. We aimed to investigate serum myeloperoxidase (MPO), catalase (CAT), and malondialdehyde (MDA) levels and their diagnostic value in schizophrenia. Methods: Sixty patients with schizophrenia, diagnosed according to DSM-V criteria, and 65 age- and sex-matched healthy controls were enrolled. Clinical severity was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI). Serum MPO and CAT were measured using ELISA, and MDA levels were determined spectrophotometrically. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. Results: Compared with controls, schizophrenia patients demonstrated significantly higher serum MDA (5.64 vs. 3.42 pg/mL, p < 0.001), MPO (77.25 vs. 31.42 ng/mL, p < 0.001), and CAT (22.06 vs. 6.58 ng/mL, p < 0.001) levels. Subgroup analysis revealed consistently increased values across patients receiving typical, atypical, or combined antipsychotics. ROC analysis indicated good diagnostic accuracy: AUC = 0.884 for MDA (cut-off: 3.79 pg/mL), AUC = 0.882 for MPO (cut-off: 34.56 ng/mL), and AUC = 0.875 for CAT (cut-off: 9.38 ng/mL), all p < 0.001. Combined analysis of MPO, CAT, and MDA yielded superior diagnostic performance (AUC = 0.995; sensitivity = 98.3%). MPO was positively correlated with PANSS-N scores (r = 0.275, p = 0.033), and both MPO and CAT were correlated with CGI severity scores. Conclusions: Elevated MPO, CAT, and MDA levels indicate increased oxidative stress in schizophrenia. MPO may also be associated with negative symptom severity. These findings suggest potential utility of oxidative stress biomarkers as adjunctive diagnostic tools, although results should be considered preliminary and validated in larger, drug-naïve, and longitudinal samples. Full article

Background: Schizophrenia is a chronic disorder requiring long-term pharmacological treatment. Many patients experience inadequate response and adverse effects, often leading to poor adherence and need for antipsychotic switch or polypharmacotherapy. In this context, brexpiprazole, an atypical antipsychotic with favorable tolerability profile, may offer clinical benefits following previous treatment failure or intolerance. However, real-world evidence after treatment switch remains limited. Methods: This retrospective, observational study included 50 outpatients with schizophrenia switched to brexpiprazole (2–4 mg/day) via cross-titration and evaluated over 12 weeks. Primary outcomes were changes in Patient Life Engagement, assessed through a 14-item subset of the Positive and Negative Syndrome Scale (PANSS), along with response/remission rates. Secondary outcomes included changes in subjective well-being, quality of life, sexual functioning (based on Subjective Well-being under Neuroleptics—Short Form [SWN-S], WHO-5 Well-Being Index [WHO-5], and Arizona Sexual Experience Scale [ASEX] scores, respectively), metabolic parameters, and prolactin levels. Results: Life engagement improved significantly (p < 0.001) across all domains, and clinical response was achieved in 40% of patients. Significant improvements were observed in SWN-S and WHO-5 scores (both p < 0.001). Weight and BMI significantly decreased (–2.64 kg, p = 0.013, and –0.91 kg/m², p = 0.006, respectively). Numerical non-significant reductions were found in ASEX (p = 0.067) and prolactin levels (–30.7 ng/mL, p = 0.077). Overall, treatment was well-tolerated. Conclusions: Switching to brexpiprazole was associated with improvements in psychopathological, functional, and physical health domains. These findings support its potential role in real-world, personalized therapeutic strategies for patients with schizophrenia following suboptimal outcomes with prior antipsychotic treatments. Full article

Background: Delirium is a rare but clinically significant complication of opioid withdrawal that remains poorly characterized in the literature. While classical withdrawal symptoms are well recognized, atypical presentations such as delirium are less frequently reported and often challenging to diagnose due to symptom overlap and heterogeneity of withdrawal syndromes. Methods: In this systematic review, we systematically analyzed available case reports and case series describing delirium precipitated by spontaneous opioid withdrawal, tapering, or antagonist-induced withdrawal. Twelve papers met inclusion criteria, comprising a total of fifteen case reports. Results: Most patients (n = 15) developed delirium within hours to days of withdrawal onset, often with fluctuating consciousness, disorientation, perceptual disturbances, and psychomotor changes. Reported risk factors included psychiatric comorbidity (major depressive disorder, anxiety disorder), concomitant use of psychotropic medication, rapid detoxification protocols, and potential exposure to adulterated substances. Management strategies varied but generally involved supportive care, benzodiazepines, antipsychotics, or reinstatement of opioid agonists. Conclusions: The findings highlight the need for heightened clinical awareness, careful differentiation from other withdrawal-related neuropsychiatric states, and systematic exclusion of organic etiologies. Despite the increasing number of patients affected by OWS, the knowledge available to date is based on case reports and a small case series, making it impossible to critically assess the prevalence or identify risk factors. Future research should aim to identify risk factors, optimize treatment, and explore novel diagnostic approaches, including AI-driven monitoring and connectomic analyses, to improve early detection and therapeutic outcomes in opioid withdrawal-associated delirium. Full article

Background: Schizophrenia (SCZ) is a psychiatric disorder that negatively impacts patients’ quality of life, frequently inducing difficulties in managing day-to-day tasks. Current research is persistently working on finding therapeutic methods to alleviate the positive and negative symptoms, as well as the associated cognitive dysfunctions. Since the main therapeutic approach in SCZ is antipsychotics, the current study aimed to explore the effects of typical (haloperidol, HAL) vs. atypical (risperidone, RIS) antipsychotics on the cognitive functions in an animal model (Danio rerio) of SCZ, obtained by ketamine (KET) administration. Methods: The cognitive evaluation of the zebrafish was performed using memory and learning tests based on two stimuli: food and colours (i.e., T memory test and novel object recognition (NOR) test, respectively). Results: According to the behavioural analyses, HAL significantly enhanced the cognitive performances of the SCZ model, as compared to RIS. Nonetheless, HAL and RIS exhibited comparable effects on social behaviour in the SCZ model. Interestingly, both HAL and RIS enhanced the interest for the novel object in the NOR test in control individuals, but significantly decreased it in the SCZ model. The interaction between KET and RIS could exhibit sedative properties. Conclusions: Both typical (HAL) and atypical (RIS) antipsychotics alleviated cognitive, socio-affective, and decision-making impairments in a ketamine-based adult zebrafish model of schizophrenia. HAL was more effective, particularly in food-stimulated decision-making compared to novel object or social stimuli. Colour influenced behavioural responses, with silver linked to prey/feeding effects and red perceived as aversive. The KET–RIS combination induced exploratory impairments, possibly due to sedative effects. These findings highlight differential pharmacological and ethological modulation of schizophrenia-like behaviours. Full article

Background/Objectives: Schizophrenia is associated with cognitive deficits that may compromise everyday functioning, including driving. This review systematically examined recent original research (2015–2025) on driving performance in individuals with schizophrenia with a focus on neuropsychological factors, applying a narrative synthesis given the heterogeneity of designs and outcomes, while no quantitative meta-analysis was feasible. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a structured search of PubMed and Scopus was conducted on 4 May 2025. The inclusion criteria were original studies involving individuals diagnosed with schizophrenia, published between 2015 and 2025. Studies on animals, other psychiatric or neurological conditions, and healthy populations were also excluded. Critical appraisal was performed using the Joanna Briggs Institute (JBI) tools. Extracted data included sample demographics, cognitive deficits, neuropsychological assessments, brain imaging, and the main findings. A narrative synthesis was then performed. Results: Six high-quality studies met the inclusion criteria. Findings were grouped into three categories: (1) driving behavior: fitness to drive varied widely across individuals, (2) cognitive deficits and brain activity: poorer driving-related performance was consistently associated with specific impairments in cognition and brain structure, and (3) medication effects: individuals taking certain atypical antipsychotics demonstrated better driving performance compared to those on other types of medication, while extrapyramidal symptoms negatively influenced driving fitness. Conclusions: Driving in schizophrenia is shaped by cognitive, clinical, and pharmacological factors. These findings highlight the clinical relevance of individualized evaluations, integration into personalized care and targeted rehabilitation to promote driving autonomy and community inclusion. This area remains under-researched, as only six studies met the inclusion criteria, which restricts the robustness and generalizability of the conclusions. Funding: This review received no funding from any external sources. Registration: The review protocol was submitted to PROSPERO (International Prospective Register of Systematic Reviews) under registration number CRD420251060580. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) characterized by oligodendrocyte (OLG) degeneration, myelin loss, and impaired remyelination. Apolipoprotein D (Apo D), a glia-derived lipocalin, has emerged in recent decades as a neuroprotective molecule involved in lipid transport, oxidative stress regulation, and inflammation control during aging and neurodegenerative diseases like MS. However, its role in demyelination/remyelination dynamics remains poorly defined. In this study, we used the cuprizone (CPZ)-induced demyelination model in C57BL/6 mice to analyze Apo D expression patterns in the corpus callosum during de- and remyelination. We also assessed whether the atypical antipsychotic clozapine (CLO), previously shown to upregulate Apo D in vivo, could modulate its expression and influence myelin recovery in this pathological context. Using a combination of magnetic resonance imaging, Luxol fast blue staining, and double immunohistochemistry, we demonstrated that CPZ treatment for 3 or 6 weeks led to significant demyelination, hydrocephalus, and reduced motor cortex thickness, which were partially reversed after treatment cessation. Apo D expression in OLGs was significantly reduced by CPZ exposure, both at the protein level and in terms of immunoreactive cell counts, but was restored following treatment withdrawal. Notably, co-administration of CLO prevented the CPZ-induced reduction in Apo D expression in OLGs, although it did not attenuate myelin loss. In this way, our results reveal a strong correlation between Apo D expression and OLG/myelin integrity in vivo. While CLO did not exert remyelinating effects, it preserved Apo D levels under demyelinating conditions, suggesting a potential indirect neuroprotective mechanism. These findings support the relevance of Apo D in CNS myelin homeostasis and highlight its potential as a molecular target for therapeutic intervention in demyelinating diseases such as MS. Full article

Background/Objectives: Psychotic disorders with childhood or adolescent onset pose major therapeutic challenges due to their complex etiology and variable treatment response. While pharmacogenetics and neuroimaging biomarkers have independently shown potential for guiding therapy, their combined utility remains underexplored. This study aimed to investigate whether integrating CYP2D6 pharmacogenetic profiles with structural neuroimaging findings can enhance personalized treatment and predict clinical outcomes in pediatric psychotic disorders. Methods: This prospective observational study included 63 children and adolescents (10–18 years) with DSM-5 diagnosed psychotic disorders. All patients underwent baseline MRI and standardized clinical assessments (PANSS, CGI, GAF). CYP2D6 genotyping was performed in 31 patients (49.2%), categorizing them as extensive (EMs) or intermediate metabolizers (IMs). Patients were treated with atypical antipsychotics and followed for 18 months. Outcomes included symptom severity, global functioning, and side-effect profiles. Results: EM patients demonstrated superior clinical improvement, as evidenced by a reduction in PANSS scores (from 118 to 40) and a corresponding increase in GAF scores (from 39 to 76), compared to the IM and non-tested groups. IM patients exhibited a higher prevalence of MRI abnormalities and slower response. Significant correlations emerged between CYP2D6 genotype, MRI findings, and treatment outcomes (p < 0.001). Combined biomarker profiles enhanced the prediction of therapeutic response and tolerability. Conclusions: Integrating CYP2D6 pharmacogenetic data with neuroimaging biomarkers provides valuable guidance for personalizing antipsychotic treatment in pediatric psychosis. This approach improves clinical outcomes and reduces adverse effects. Future research should further explore the integration of multimodal biomarkers in larger, longitudinal cohorts to optimize individualized psychiatric care for this vulnerable population. Full article

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