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Microneedles (MNs) are minimally invasive transdermal drug delivery systems capable of penetrating the stratum corneum to overcome the barrier properties. The primary objective of this research was to prepare dissolving microneedle patches (DMNP) loaded with quetiapine (QTP). DMNP were fabricated employing the solvent casting technique, utilizing various polymer feed ratios including polyvinyl alcohol (PVA), polyvinylpyrrolidone K30 (PVP-K30), and polylactide-co-glycolide (PLGA) polymers. The loaded DMNP with QTP underwent a comprehensive characterization process encompassing assessments for compatibility, thickness, insertion potential, morphology, thermal behavior, X-ray diffraction, ex-vivo permeation, skin irritation, and histopathological changes. FTIR studies confirmed the compatibility of QTP with the microneedle patch composites. The thickness of the drug-loaded DMNP ranged from 0.67 mm to 0.97 mm. These microneedles exhibited an impressive penetration depth of 480 μm, with over 80% of the needles maintaining their original shape after piercing Parafilm-M. SEM analysis of the optimized DMNP-2 revealed the formation of sharp-tipped and uniformly surfaced needles, measuring 570 μm in length. Remarkably, the microneedles did not elicit any signs of irritation upon application of the prepared DMNP. The DMNP-2 showcased an impressive cumulative ex-vivo permeation of QTP, reaching 17.82 µg/cm2/hr. Additionally, histopathological assessment of vital organs in rabbits attested to the safety profile of the formulated microneedle patches. In conclusion, the developed microneedle patch represents a promising strategy for enhancing the transdermal delivery of QTP. This innovative approach has the potential to increase patient compliance, offering a more efficient and patient-friendly method of administering QTP. [ABSTRACT FROM AUTHOR]

Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs. We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280. We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82–1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09–1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92–2.25]). In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs. • Differences in the incidence of new-onset diabetes caused by second-generation antipsychotics were compared. • Clozapine and olanzapine cause a similar incidence of new-onset diabetes. • Clozapine is more likely to cause new-onset diabetes than risperidone. • Explored relationship between therapy duration and incidence [ABSTRACT FROM AUTHOR]

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD. [ABSTRACT FROM AUTHOR]

Quetiapine monotherapy is recommended as the first-line option for acute mania and acute bipolar depression. However, the mechanism of action of quetiapine is unclear. Network pharmacology and molecular docking were employed to determine the molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania. Putative target genes for quetiapine were collected from the GeneCard, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and bipolar mania were identified from the DisGeNET and GeneCards databases. A protein-protein interaction (PPI) network was generated using the String database and imported into Cytoscape. DAVID and the Bioinformatics platform were employed to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the top 15 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the interactions between quetiapine and potential targets. Targets for quetiapine actions against bipolar depression (126 targets) and bipolar mania (81 targets) were identified. Based on PPI and KEGG pathway analyses, quetiapine may affect bipolar depression by targeting the MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, and NGF, and it may affect bipolar mania by targeting the neuroactive ligand-receptor interaction signaling pathway via HTR1A, HTR1B, HTR2A, DRD2, and GRIN2B. Molecular docking revealed good binding affinity between quetiapine and potential targets. Pharmacological experiments should be conducted to verify and further explore these results. Our findings suggest that quetiapine affects bipolar depression and bipolar mania through distinct biological core targets, and thus through different mechanisms. Furthermore, our results provide a theoretical basis for the clinical use of quetiapine and possible directions for new drug development. • Quetiapine affects bipolar depression and bipolar mania through different mechanisms. • Quetiapine affects depression by targeting MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, NGF. • Quetiapine affects mania through neuroactive ligand-receptor interaction pathway via HTR1A, HTR1B, HTR2A, DRD2, GRIN2B. [ABSTRACT FROM AUTHOR]

There is great interindividual difference in the plasma concentration of quetiapine, and optimizing quetiapine therapy to achieve a balance between efficacy and safety is still a challenge. In our study, a population pharmacokinetic (PPK) model considering genetic information was developed with the expectation of comprehensively explaining this observation in Chinese patients with bipolar disorder. Patients who were dispensed quetiapine and underwent the therapeutic drug monitoring (TDM) were included. The genotypes of CYP3A5*3 , CYP2D6*10 , and ABCB1 C3435T/G2677T were analyzed. Finally, a multivariable linear regression model was applied to describe the PPK of quetiapine considering the covariates weight, height and genotype information. A total of 175 TDM points from 107 patients were adopted for PPK model development. Resultantly, the CL/F of quetiapine in CYP3A5 expressers was 81.1 CL/h, whereas it was 43.6 CL/h in CYP3A5 nonexpressers. The interindividual variability in CL/F was 47.7 %. However, neither the ABCB1 nor CYP2D6 genotype was significantly associated with the predictor of quetiapine clearance in our study. Only trough concentrations were collected, and the span between different points was relatively wide, impeding the application of the typical nonlinear compartment model for PPK analysis. In addition, this was a single-center study which limited the sample of wild-type CYP3A5 carriers. The currently established PPK model of quetiapine considering the contribution of the CYP3A5 genotype could efficiently predict the population and individual pharmacokinetic parameters of Chinese bipolar disorder patients, which could better guide the personalized therapy with quetiapine, thus to achieve the best clinical response. [ABSTRACT FROM AUTHOR]

This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP). We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials investigating SGAs for PDP up to October 26, 2023. We included 16 trials (N = 1252) investigating clozapine, melperone, olanzapine, pimavanserin, quetiapine, ulotaront, and placebo. In comparisons between SGAs and placebo, the findings were: i) Standardized mean differences, 95% confidence intervals (SMDs, 95%CIs), for psychotic-symptom reduction revealed the first rank of clozapine (−1.31, −1.73 to −0.89), the second rank of pimavanserin, with significant inferiority of quetiapine (SMD = 0.47, 0.02 to 0.92); ii) Mean differences (MDs, 95%CIs) for abnormal movement, as assessed by the Unified Parkinson's Disease Rating Scale – Part III, indicated that clozapine had the least motor side effects (−0.92, −2.75 to 0.91); iii) Risk ratios (RRs, 95% CIs) for adverse-effect dropout rates were lowest for melperone (1.02, 0.20 to 5.24); and iv) RRs (95% CIs) for all-cause dropout rates were lowest for clozapine (0.73, 0.42 to 1.25). For patients with PDP, clozapine may substantially reduce psychotic symptoms with minimal abnormal movement, high acceptability, and moderate overall tolerability. Pimavanserin, not quetiapine, could be an alternative. • Clozapine tops other second-generation antipsychotics (SGAs) in reducing Parkinson's disease psychosis (PDP). • Pimavanserin is superior to placebo and quetiapine in reducing PDP. • For PDP, clozapine shows minimum motor side effects and fewer dropouts than other SGAs. • Among SGAs, clozapine exhibits a moderate level of overall tolerability for PDP. • Clozapine and pimavanserin, not quetiapine, may be the SGAs of choice for PDP. [ABSTRACT FROM AUTHOR]

Case reports suggest that quetiapine or haloperidol use is associated with severe QT prolongation (SQTP) and torsades de pointes. The purpose of this study was to examine the incidences, risk factors, and outcomes of SQTP in quetiapine and haloperidol users. This study accessed electronic medical records from a multicenter health-care hospital system in Taiwan and included patients who received quetiapine or haloperidol therapy and had both baseline and follow-up electrocardiograms. SQTP was defined as a posttreatment corrected QT (QTc) interval exceeding 500 ms or an increase in QTc interval of >60 ms compared with the baseline value. We analyzed the risk factors and outcomes of SQTP using multivariate logistic regression. Mean increases in QTc interval were +8.3 ± 51.8 and +8.9 ± 44.0 ms after the administration of quetiapine (n = 8832) and haloperidol (n = 2341). Among these users, 1149 (13.0%) and 333 (14.2%) developed SQTP, respectively. Common risk factors for SQTP included old age, heart failure, hypokalemia, amiodarone use, and baseline QTc interval. SQTP in quetiapine users was significantly associated with ventricular arrhythmias (odds ratio 2.84; 95% confidence interval 1.95–4.13) and sudden cardiac death (odds ratio 2.29; 95% confidence interval 1.44–3.66). More than 10% of patients receiving quetiapine or haloperidol therapy developed SQTP, and many of them were exposed to risk factors for SQTP. SQTP in quetiapine users was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death. Clinicians should be vigilant for ventricular arrhythmias in quetiapine users who have risk factors for SQTP. [Display omitted] [ABSTRACT FROM AUTHOR]

Individuals receiving hemodialysis have high rates of sudden cardiac death (SCD). This study characterized oral atypical antipsychotic use and compared the cardiac safety of atypical antipsychotics with QT prolongation FDA warnings to that of atypical antipsychotics without such warnings among outpatients receiving hemodialysis. Data for this active-comparator, new-user cohort study were obtained from the U.S. Renal Data System (2007–2019). The primary outcome was 1-year SCD risk. Fine and Gray proportional subdistribution hazard models with inverse probability of treatment weighting were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). The quetiapine vs. atypical antipsychotics without QT prolongation warnings cohort included 18,943 quetiapine new-users and 19,571 non-warning atypical antipsychotic new-users. When compared to new-use of atypical antipsychotics without QT prolongation warnings, quetiapine new-use was not associated with the risk of SCD (aHR (95% CI) = 1.00 (0.93, 1.07)) or broader cardiac outcomes. Comparisons of all atypical antipsychotics with QT prolongation warnings vs. atypical antipsychotics without warnings generated similar results. Quetiapine, which carries an FDA warning for QT prolongation, did not associate with cardiac risk compared to atypical antipsychotics without warnings among hemodialysis outpatients. Findings may inform prescriber selection of atypical antipsychotics in this population. [ABSTRACT FROM AUTHOR]

Low-dose lithium (LD-Li) has been shown to rescue cognitive impairment in mouse models of short-term mild cognitive impairment, dementia, and schizophrenia. However, few studies have characterized the effects of LD-Li, alone or in conjunction with anti-psychotics, in the mouse model of MK801-induced long term cognitive impairment. The present study used in vivo Ca2+ imaging and a battery of cognitive function assessments to investigate the long-term effects of LD-Li on cognition in mice exposed to repeated injections of MK801. Prefrontal Ca2+ activity was visualized to estimate alterations in neural activity in the model mice. Pre-pulse inhibition (PPI), novel object recognition (NOR), Morris water maze (MWM), and fear conditioning (FC) tasks were used to characterize cognitive performance; open field activity (OFA) testing was used to observe psychotic symptoms. Two treatment strategies were tested: LD-Li [250 mg/d human equivalent dose (HED)] adjunct to quetiapine (QTP; 600 mg/d HED); and QTP-monotherapy (mt; 600 mg/d HED). Compared to the QTP-mt group, the LD-Li + QTP group showed greatly improved cognitive performance on all measures between experimental days 29 and 85. QTP-mt improved behavioral measures compared to untreated controls, but the effects persisted only from day 29 to day 43. These data suggest that LD-Li + QTP is superior to QTP-mt for improving long-term cognitive impairments in the MK801 mouse model. There is no medical consensus regarding lithium use in patients with schizophrenia. More pre-clinical and clinical studies are needed to further investigate effective treatment strategies for patients with long-term cognitive impairments, such as chronic schizophrenia. • LD-Li + QTP rescues MK801-induced long-term cognitive impairment. • LD-Li + QTP is superior to QTP-mt for improving cognition in a mouse model. • Quetiapine with or without adjunct lithium improves schizophrenia-like behavior. [ABSTRACT FROM AUTHOR]

Few studies have evaluated lithium either as monotherapy or in combination with anti-psychotic agents to improve cognition in murine models of schizophrenia. Visualization of Ca2+ activity in the prefrontal cortex was used to characterize brain neural activity. Novel object recognition (NOR), Morris water maze (MWM), and fear conditioning (FCT) tests were used to characterize cognitive performance; while pre-pulse inhibition (PPI), elevated plus maze (EPM) and the open field test (OFT) were used to characterize schizophrenia-like behavior. A 28-day course of low-dose lithium (human equivalent dose of 250 mg/day) combined with moderate-dose quetiapine (human equivalent dose of 600 mg/day) improved Ca2+ ratio by 70.10 %, PPI by 69.28 %, NOR by 70.09 %, MWM by 71.28 %, FCT by 68.56 %, EPM by 70.95 % and OFT by 75.23 % compared to the results of positive controls. Unexpectedly, moderate-dose lithium (human equivalent dose of 500 mg/day) used either as monotherapy or as an adjunct with quetiapine worsened Ca2+ activity, PPI, MWM, FCT, EPM, and OPT. Our study cannot explain the contrasting positive and negative effects of low-dose and moderate-dose lithium, respectively, when used either as monotherapies or as adjuncts. Further studies, especially Western blotting, may reveal molecular mechanisms of action. Low-dose lithium (human equivalent dose of 250 mg/day) combined with moderate-dose quetiapine (human equivalent dose of 600 mg/day) provided the best improvements. Furthermore, benefits persisted for 14 days post-treatment. Our data provide directions for further research of therapeutic alternatives to mitigate schizophrenia-related cognopathy. • Cognitive impairment is a major complication of schizophrenia. • Lithium can improve cognitive impairments (CI) of dementia. • We postulated that lithium can improve CI in MK801 mouse. • Our data demonstrated that low-dose lithium can improve CI in MK801 mouse. • Unexpectedly, moderate lithium deteriorated CI in MK801 mouse. [ABSTRACT FROM AUTHOR]

The treatment of bipolar depression is one of the most challenging needs in contemporary psychiatry. Currently, only quetiapine, olanzapine-fluoxetine combination, lurasidone, cariprazine, and recently lumateperone have been FDA-approved to treat this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of cariprazine fit into a previously developed model which was the first to be derived based on the strict combination of clinical and preclinical data. The authors performed a systematic review of the literature to identify the pharmacodynamic properties of cariprazine. The original model suggests that a constellation of effects on different receptors is necessary and that serotonin reuptake inhibition does not appear to play a significant role in acute bipolar depression. On the contrary, norepinephrine activity seems to be necessary. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition appears essential to sustain it. Overall, the properties of cariprazine fit well the proposed model and add to its validity. A point that needs further clarification is norepinephrine reuptake inhibition which is not yet fully studied for cariprazine. [ABSTRACT FROM AUTHOR]

The second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) — a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. Using the ACC as region of interest, an independent t -test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. Left subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. Causal interpretation is limited due to cross-sectional findings. Elevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes. • Quetiapine exerts antidepressant properties critical for augmentation therapy in MDD. • The rostral ACC is a key interface in antidepressant treatment and reward processing. • In MDD, quetiapine intake was associated with reward-related subgenual ACC activity. • Differences were specific for positive stimulus response and high dose treatment. • Subgenual ACC reward response may represent quetiapine's antidepressant effect in MDD. [ABSTRACT FROM AUTHOR]

It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage. The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively. 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (r s = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization. We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression. • This is the first study about the relationship between TDM of quetiapine and clinical treatment response in BD. • The main finding is that there is a correlation between TDM of quetiapine and clinical outcome in bipolar disorders. [ABSTRACT FROM AUTHOR]

• Quetiapine improves sleep. • Potent in older ages and males. • Initial dosage: 50-150 mg/day. Quetiapine is a common off-label antipsychotic drug for treating insomnia. Its effects in different disease conditions and dosages remain unclear. We conducted a systematic review and meta-analysis in clinical trials examining the efficacy of low-dose quetiapine in sleep. We obtained 21 clinical trials. Mean difference (MD), standard mean difference (SMD), and odds ratio (OR) were used to estimate the effect sizes using a random-effects model. The pooled results showed that quetiapine improved sleep quality compared with placebo (SMD: -0.57 [95%CI: -0.75, -0.4]). The SMD of sleep quality was correlated with age (coefficient: -0.0174) and sex (coefficient: -0.012). The significant effects were observed in the general anxiety disorder (SMD: -0.59 [95%CI: -0.92, -0.27]), major depressive disorder (SMD: -0.47 [95%CI: -0.66, -0.28]), and healthy (SMD: -1.33, [95%CI [-2.12, -0.54]) subgroups, at the dosage of 50 mg (SMD: -0.36 [95%CI: -0.36, -0.11]), 150 mg (SMD: -0.4 [95%CI: -0.52, -0.29]), and 300 mg (SMD: -0.17 [95%CI: -0.31,-0.04]). Quetiapine increased total sleep time compared with placebo (MD: 47.91 [95%CI: 28.06, 67.76]) but not when compared with other psychiatric drugs (MD: -4.19 [95%CI: -19.43, 11.05]). Adverse events (AEs) and discontinuation due to AEs were common among the quetiapine users. Quetiapine is effective as a sleep-helping drug. Precaution is suggested when interpreting the results on the elderly due to the high heterogeneity caused by incorporating patients over 66 years in the meta-analyses. We recommend an initial dosage of 50-150 mg/day with priority consideration for the elderly with GAD or MDD while monitoring its potential AEs. [ABSTRACT FROM AUTHOR]

Chronic antipsychotic use among nursing home (NH) residents carries risks with uncertain benefits. Despite guidelines recommending restricted use, these agents remain widely prescribed. This study investigates chronic antipsychotic use in Belgian NHs. We examined the evolution of chronic antipsychotic use, associated NH resident profiles, impact of NH admissions, and variation among Belgian NHs in a retrospective dynamic cohort study between 2017 and 2022. Antipsychotic dispensation rates were extracted for members of the Independent Health Insurance Funds in NHs. Prescription trends and resident profiles were evaluated for around 15,000 residents yearly (n = 14,733-15,451) from 2017 to 2022 and variation was assessed among 59 NHs. The impact of NH admission was analyzed for 9647 admissions between 2020 and 2022, and variation was evaluated among 22 NHs. For 22 antipsychotics identified at the ATC3 level, chronic use was defined as ≥80 defined daily doses (DDD) and/or ≥16 weekly dispensations per year. We analyzed changes in the 4 most frequently used antipsychotics (haloperidol, olanzapine, quetiapine, risperidone) on NH admission, with chronic use defined as ≥80 minimal prescribed doses (MPD) annually. The prevalence of chronic antipsychotic use among NH residents decreased from 24% in 2017 to 22.5% in 2022 (P =.002). Factors associated with higher antipsychotic use included younger age, greater dependency, and lower socioeconomic status. Upon NH admission, 30% (n = 818 of 2723) of residents discontinued treatment, while in 33% (n = 949 of 2854) treatment was initiated, predominantly with quetiapine or risperidone. This led to a small but significant increase of 1.4% after admission (P <.001). Defining chronic use as ≥80 MPD annually appeared to be more sensitive in measuring chronic antipsychotic use. Chronic antipsychotic use remains widespread in Belgian NHs, with care transition as an important decision point. Further research should explore effects of safer (de)prescribing strategies on patient well-being. [ABSTRACT FROM AUTHOR]

The review of the literature by He and colleagues (Association of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine versus patients treated with olanzapine, risperidone, or quetiapine: a systematic review and meta-analysis) found that in patients with schizophrenia, clozapine is associated with a higher rate of new-onset diabetes mellitus compared to risperidone, but not in comparison to olanzapine or quetiapine, pointing to the importance of balancing risks and benefits in using these drugs. [ABSTRACT FROM AUTHOR]

• Here, we examined rates of death due to choking (i.e. death by asphyxiation, defined according to ICD-10 codes) in schizophrenia. • Schizophrenia was associated with a 20-fold increase in risk of death by asphyxiation relative to the general population. • Death by asphyxiation risks were relatively high during use of strong dopamine-2 receptor antagonist antipsychotics. • Relative to nonuse, death by asphyxiation risk was not elevated during use of weak or moderate dopamine-2 receptor antagonists. • Clinical implications of these results include the need to address eating habits and try and prevent infections in at-risk patients. The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related standardized mortality ratio for schizophrenia relative to the general population (SMR choking). We also computed adjusted hazard ratios (aHR) of choking-related mortality for antipsychotics in a nationwide cohort of patients with schizophrenia (N = 59,916). SMR choking was 20.5 (95 % confidence interval (CI)=17.1–23.9). The aHR was 1.74 (95 %CI=1.19–2.55) for strong dopamine 2-antagonists. For other antipsychotics, CIs included 1. Importantly, aHRs were particularly high for high dose categories of strong dopamine D2 receptor (D2R) antagonists. In conclusion, a schizophrenia diagnosis is associated with a 20-fold risk of death due to choking. This risk is elevated during use of strong D2R antagonist antipsychotics, particularly when prescribed in high dosages. [ABSTRACT FROM AUTHOR]

Objective: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established.Method: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition.Results: At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls.Conclusion: Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD.Clinical Trial Registration Information: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581. [ABSTRACT FROM AUTHOR]

• One in six residents of nursing homes use strong anticholinergic medications. • There was a 20-fold variation in prevalence across the 12 countries. • Antipsychotics and antidepressants were the most common strong anticholinergics. There is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty. Secondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0–2 (non-frail), 3–6 (frail) and 7–14 (most-frail). Data were analyzed using descriptive statistics. Overall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %). One in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs often lead to adverse effects, including those related to the cardiovascular system. Of these, quetiapine is known to cause significant changes in the QT interval although the underlying mechanism remains mysterious, prompting us to examine its effects on cardiac electrophysiological properties. Therefore, we investigated the effect of quetiapine on contraction, action potential (AP), and the associated membrane currents such as L-type Ca2+ and K+ using the whole-cell patch clamp method to examine its impacts on isolated rat ventricular myocytes. Our results showed that (1) quetiapine reduces cell contractility in a concentration-dependent manner and (2) leads to a significant prolongation in the duration of AP in isolated ventricular myocytes. This effect was both concentration and frequency-dependent; (3) quetiapine significantly decreased the Ca2+, transient outward K+, and steady-state K+ currents. However, only high concentration of quetiapine (100 μM) could significantly change the activation and reactivation kinetics of L-type Ca2+ channels. This study demonstrates that QT extension induced by quetiapine is mainly associated with the prolongation of AP. Moreover, quetiapine caused a significant decrease in contractile force and excitability of ventricular myocytes by suppressing Ca2+ and K+ currents. [ABSTRACT FROM AUTHOR]

• This meta-analysis was to explore the relationship between psychiatric medications and the risk of falls and fractures in people taking them. • Typical antipsychotics, atypical antipsychotics and antidepressants are associated with the risk of falls. • Typical antipsychotics and atypical antipsychotics were associated with the risk of fractures. • Atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. • Quetiapine and class z drugs may be the drugs with the highest risk of falls and fractures, respectively. An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest risk of falls or fractures should be further investigated. The aim of this study was to compare and rank the magnitude of risk of falls and fractures due to different psychiatric medications. Eight databases were searched for this meta-analysis and evaluated using a frequency-based network meta-analysis. The results included a total of 28 papers with 14 medications from 5 major classes, involving 3,467,314 patients. The results showed that atypical antipsychotics were the class of medications with the highest risk of falls, and typical antipsychotics were the class of medications with the highest risk of resulting in fractures. Quetiapine ranked first in the category of 13 medications associated with risk of falls, and class Z drugs ranked first in the category of 6 medications associated with risk of fractures. The available evidence suggests that atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. Quetiapine may be the medication with the highest risk of falls, and class Z drugs may be the medication with the highest risk of fractures. [ABSTRACT FROM AUTHOR]

Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64–1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37–0.87, P = 0.010) whereas treatment for 6–12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22–2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06–1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses. • Off-label, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. • Treatment status (treated vs untreated) was not significantly associated with cardiometabolic mortality. • Treatment for 6–12 months was significantly associated with an increased risk compared to no treatment. • Among those treated, each year exposed was significantly associated with an increased risk. • Clinicians should consider cardiometabolic consequences regardless of prescribed dose or length of treatment. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response.Methods: We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models.Results: Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response.Limitations: Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors.Conclusions: Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of quetiapine treatment on central set point of thyroid homeostasis in patients with acute phase schizophrenia.Methods: During Jan. 2016 to Dec. 2018, we conducted a retrospective cohort study in "the Second Affiliated Hospital of Xinxiang Medical University". All patients admitted for treatment of schizophrenia being euthyroid at admission and reevaluated for thyroid function during hospitalization were recruited and followed until discharge. Patients treated with mood stabilizers during hospitalization were excluded. Quetiapine use was the exposure measure. The primary outcomes were the parameters of central set point of thyroid homeostasis measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index (TFQI)". Multiple regression models were used to estimate the association between quetiapine exposure and outcomes.Results: A total of 1302 patients were enrolled in this study. Quetiapine exposure was associated with a more significant decline in the TSH index and TFQI, and the adjusted β and 95% confidence interval (CI) were -0.12 (-0.22, -0.01) and -0.10 (-0.15, -0.05), respectively. A dose-response association between quetiapine exposure and decline in TSH index and TFQI was observed (P < 0.05). Sensitivity analyses restricting to patients under mono-atypical antipsychotic therapy, or selecting patients in the non-quetiapine group matched to quetiapine group yielded similar results.Conclusion: Quetiapine was associated with TSH index and TFQI reduction in a dose-response pattern, suggesting that impaired central set point may be involved in the mechanism by which quetiapine affects hypothalamus-pituitary-thyroid axis in acute phase schizophrenia patients. [ABSTRACT FROM AUTHOR]

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1–12 weeks and followed-up for 24–104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34–0.51, p <0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19–0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25–0.55, p <0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663. [ABSTRACT FROM AUTHOR]

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder. [ABSTRACT FROM AUTHOR]

Quetiapine hemifumarate (QF) delivery to the CNS via conventional formulations is challenging due to poor solubility and lower oral bioavailability (9 %). Similarly, many other second-generation antipsychotics, such as olanzapine, clozapine, and paliperidone, have also shown low oral bioavailability of <50 %. Hence, the present work was intended to formulate QF-loaded biodegradable PLGA-NPs with appropriate surface charge modification through poloxamer-chitosan and investigate its targeting potential on RPMI-2650 cell lines to overcome the limitations of conventional therapies. QF-loaded poloxamer-chitosan-PLGA in-situ gel (QF-PLGA-ISG) was designed using emulsification and solvent evaporation techniques. Developed QF-PLGA-ISG were subjected to evaluation for particle size, PDI, zeta potential, ex-vivo mucoadhesion, entrapment efficiency (%EE), and drug loading, which revealed 162.2 nm, 0.124, +20.5 mV, 52.4 g, 77.5 %, and 9.7 %, respectively. Additionally, QF-PLGA formulation showed >90 % release within 12 h compared to 80 % of QF-suspension, demonstrating that the surfactant with chitosan-poloxamer polymers could sustainably release medicine across the membrane. Ex-vivo hemolysis study proved that developed PLGA nanoparticles did not cause any hemolysis compared to negative control. Further, in-vitro cellular uptake and transepithelial permeation were assessed using the RPMI-2650 nasal epithelial cell line. QF-PLGA-ISG not only improved intracellular uptake but also demonstrated a 1.5–2-fold increase in QF transport across RPMI-2650 epithelial monolayer. Further studies in the EpiNasal™ 3D nasal tissue model confirmed the safety and efficacy of the developed QF-PLGA-ISG formulation with up to a 4-fold increase in transport compared to plain QF after 4 h. Additionally, histological reports demonstrated the safety of optimized formulation. Finally, favorable outcomes of IN QF-PLGA-ISG formulation could provide a novel platform for safe and effective delivery of QF in schizophrenic patients. [Display omitted] • Development of quetiapine hemifumarate (QF) poloxamer-chitosan poly (lactic- co -glycolic acid) nanoparticles (QF-PLGA-ISG). • QF-PLGA-ISG revealed safe and effective uptake and permeation against RPMI-2650 cell lines and MatTek EpiNasal™ tissues. • Intranasal (IN) QF-PLGA-NPs and QF-PLGA-ISG improved the delivery of QF in brain disorders. • IN QF-PLGA-NPs administration could reduce QF systemic exposures and associated side effects. [ABSTRACT FROM AUTHOR]

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment. • It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. • We investigated white matter and S100B changes and associations before and after treatment in schizophrenia patients. • Following effective treatment, the recovery of S100B and WM fiber connections in some brain regions occurred. • The recovery of S100B and WM were correlated with an improvement in symptoms. • The changes of S100B and WM can help us to explore the neurobiological mechanisms of schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia has been linked to cognitive impairment and white matter damage in a growing number of studies this year. In this study, we used the MK-801-induced schizophrenia-like mice model to investigate the effects of quetiapine on behavioral changes and myelin loss in the model mice. The subjects selected for this study were C57B6/J male mice, MK-801 (1 mg/kg/d intraperitoneal injection) modeling for 1 week and quetiapine (10 mg/kg/d intraperitoneal injection) treatment for 2 weeks. Behavioral tests were then performed using the three-chamber paradigm test and the Y maze test. Moreover, western blot, immunohistochemistry, and immunofluorescence were conducted to investigate the changes in oligodendrocyte spectrum markers. In addition, we performed some mechanism-related proteins by western blot. Quetiapine ameliorated cognitive impairment and cerebral white matter damage in MK-801 model mice, and the mechanism may be related to the PI3K/AKT pathways. The present study suggests that quetiapine has a possible mechanism for treating cognitive impairment and white matter damage caused by schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population.Methods: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events.Results: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002).Conclusions: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients. [ABSTRACT FROM AUTHOR]

The use of antipsychotic medications (APMs) could be different among countries due to availability, approved indications, characteristics and clinical practice. However, there is limited literature providing comparisons of APMs use among countries. To examine trends in antipsychotic prescribing in Taiwan, Hong Kong, Japan, and the United States, we conducted a cross-national study from 2002 to 2014 b y using the distributed network approach with common data model. We included all patients who had at least a record of antipsychotic prescription in this study, and defined patients without previous exposure of antipsychotics for 6 months before the index date as new users for incidence estimation. We calculated the incidence, prevalence, and prescription rate of each medication by calendar year. Among older patients, sulpiride was the most incident [incidence rate (IR) 11.0–23.3) and prevalent [prevalence rate (PR) 11.9–14.3) APM in Taiwan, and most prevalent (PR 2.5–3.9) in Japan. Quetiapine and haloperidol were most common in the United States (IR 8.1–9.5; PR 18.0–18.4) and Hong Kong (PR 8.8–13.7; PR 10.6–12.7), respectively. The trend of quetiapine use was increasing in Taiwan, Hong Kong and the United States. As compared to older patients, the younger patients had more propensity to be prescribed second-generation APM for treatment in four countries. Trends in antipsychotic prescribing varied among countries. Quetiapine use was most prevalent in the United States and increasing in Taiwan and Hong Kong. The increasing use of quetiapine in the elderly patients might be due to its safety profile compared to other APMs. [ABSTRACT FROM AUTHOR]

• Quetiapine lowers myelin, transthyretin, and copper transporter gene expression. • Dysbindin-1 knockout and quetiapine treatment alter serum copper levels. • Loss of dysbindin-1 expression results in hyperactive mice. • Dysbindin-1 loss impairs neurological function; quetiapine selectively rescues it. DTNBP1 gene variation and lower dysbindin-1 protein are associated with schizophrenia. Previous evidence suggests that downregulated dysbindin-1 expression results in lower expression of copper transporters ATP7A (intracellular copper transporter) and SLC31A1 (CTR1; extracellular copper transporter), which are required for copper transport across the blood brain barrier. However, whether antipsychotic medications used for schizophrenia treatment may modulate these systems is unclear. The current study measured behavioral indices of neurological function in dysbindin-1 functional knockout (KO) mice and their wild-type (WT) littermates with or without quetiapine treatment. We assessed serum and brain copper levels, ATP7A and CTR1 mRNA, and copper transporter-expressing cellular population transcripts: TTR (transthyretin; choroid plexus epithelial cells), MBP (myelin basic protein; oligodendrocytes), and GJA1 (gap-junction protein alpha-1; astrocytes) in cortex and hippocampus. Regardless of genotype, quetiapine significantly reduced TTR, MBP, CTR1 mRNA, and serum copper levels. Neurological function of untreated KO mice was abnormal, and ledge instability was rescued with quetiapine. KO mice were hyperactive after 10 min in the open-field assay, which was not affected by treatment. Dysbindin-1 KO results in hyperactivity, altered serum copper, and neurological impairment, the last of which is selectively rescued with quetiapine. Antipsychotic treatment modulates specific cellular populations, affecting myelin, the choroid plexus, and copper transport across the blood brain barrier. Together these results indicate the widespread impact of antipsychotic treatment, and that alteration of dysbindin-1 may be sufficient, but not necessary, for specific schizophrenia pathology. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder.Methods: The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response.Results: Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms.Conclusions: Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history. [ABSTRACT FROM AUTHOR]

Sleep walking (SW) is a parasomnia behavior characterized by repetitious occurrence of ambulation during a partial arousal from non-rapid eye movement (NREM) sleep. Sleep-related eating (SRE) is one of the complex sleep behaviors that may accompany SW. Emerging evidence suggests that NREM parasomnias can be associated with atypical antipsychotic medication use. We present a case series (n = 5) and a systematic review of the literature of cases of SW, with or without SRE (n = 23), associated with atypical antipsychotic use. Twenty-eight cases of SW, with and without SRE, with a mean age of 44.8 years (S.D. = 15.04) and a male predominance (75%; n = 21) were identified. Quetiapine was the most commonly implicated medication with SW and SRE (n = 14). Remission from SW/SRE was noted in all cases with measures including antipsychotic dosage reduction, discontinuation of medication, switching to an alternate medication, and use of continuous positive airway pressure (CPAP) for comorbid obstructive sleep apnea (OSA) treatment. Sleep walking (SW), with or without sleep related eating (SRE), can be a rare but reversible side effect associated with use of atypical antipsychotics. More research is warranted to elucidate the mechanisms underlying SW and SRE associated with atypical antipsychotic use. [ABSTRACT FROM AUTHOR]

Background: Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior.Methods: We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures.Results: On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 = 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p = 0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only, F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating.Limitations: Bipolar CHOICE was not designed to study anthropometric outcomes.Conclusions: Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline. [ABSTRACT FROM AUTHOR]

Lipid core nanocapsules (LNC) have been extensively studied as a new treatment strategy to improve therapeutic effects of antipsychotic drugs. We investigated the efficacy of quetiapine LNCs (QLNCs) on the poly(i:c) model of schizophrenia in both male and female rats using the pre-pulse inhibition of startle response (PPI) test paradigm after evaluating the outcomes of three different poly(i:c) doses administered to pregnant damns at GD15 on neurodevelopmental outcomes of maternal immune activation (MIA) in adult offspring. QTP solution was not capable of producing a reversal in the sensorimotor gating-disruptive effect caused by the prenatal poly(i:c) exposure. The same dose of QTP given as QLNCs significantly improved PPI-impairment. This is the first study reporting the restoration of the PPI deficits in a neurodevelopmental model of SCZ using LNCs. This is a promising delivery system strategy to improve antipsychotic effects contributing to the development of better SCZ pharmacological treatments. [ABSTRACT FROM AUTHOR]

In this research, the advantages of molecularly imprinted polymer (MIP) materials have been used to develop a new electrochemical sensor for determination of quetiapine (QTP) drug. MIP nanoparticles were synthesized by precipitation polymerization method and used as QTP recognition elements in the composition of modified carbon paste electrode (CPE) for selective and sensitive assay of this drug. Cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were used for electrochemical analysis. Some parameters affecting the sensor performance were optimized and under optimal conditions, the proposed sensor showed linear responses with QTP concentration in the range of 1.6 × 10−8 to 2.5 × 10−6 M (R2 = 0.9964). The limits of detection (LOD) and quantification (LOQ) were calculated 5.04 × 10−9 M and 1.68 × 10−8 M respectively. Also, the amounts of %RSD for evaluation of repeatability and reproducibility of the proposed sensors were respectively obtained 2.19 and 3.02%. The method was successfully applied to determination of QTP in its pharmaceutical formulation and human urine samples. Image 1 • Molecularly imprinted polymers (MIP) materials were synthesized for the quetiapine (QTP) antipsychotic drug for the first time. • Development of a simple, inexpensive and promising electrochemical sensing design for QTP. • Significantly enhanced selectivity towards the target molecule due to predetermined identification properties. • Good capability of the proposed sensor for determination of the quetiapine in different real samples. [ABSTRACT FROM AUTHOR]

Introduction: Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI.Methods: 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures.Results: Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI.Limitations: Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk.Discussion: Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies.Methods: Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available.Results: Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001).Conclusion: Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quetiapine hemifumarate Nanoemulgel (QF-Nanoemulgel) was formulated successfully after carefully considering the polymers. • Successful implementation of regulatory mandated (ICH Q8-R2) quality-by-design approach for optimization of QF-Nanoemulgel. • Optimized formulations demonstrated favorable safety profiles and efficient internalization in RPMI-2650 nasal cell lines. • Permeation evidence supported the targeted delivery of QF towards the brain via bypassing barriers. • Intranasal administration of QF-Nanoemulgel effectively mitigated peripheral exposure to QF and its associated effects. Second-generation antipsychotics, quetiapine hemifumarate (QF), exhibited highly active against negative and positive signs of psychosis. However, contemporary reports have shown that long-term therapy with QF causes lethal thrombocytopenia and leukopenia. Hence, to circumvent the drawbacks of available therapies, the current work aimed to design a QF-loaded biodegradable nanoemulsion (QF-NE) with suitable surface charge modification by poloxamer-chitosan and evaluate its targeting efficiency against RPMI-2650 cell lines. QF-loaded poloxamer-chitosan in-situ gel (QF-Nanoemulgel) was formulated through the O/W emulsification aqueous titration technique and optimized using the QbD approach. Optimized QF-Nanoemulgel subjected to evaluate for globule size, PDI, zeta potential, %T, viscosity, %EE, and ex-vivo mucoadhesive strength were found to be 15.0 ± 0.3 nm, 0.05 ± 0.001, −18.3 ± 0.2 mV, 99.8 ± 0.8 %, 13.5 ± 2.1 cP, 69.0 ± 1.5 %, and 43.7 ± 1.5 g, respectively. QF-Nanoemulgel revealed sustained release and obeyed zero-order kinetics compared to QF-NE and QF-suspension. Additionally, nanoformulations treated blood samples did not cause hemolytic activity compared to drug and negative control after 10 h treatment. Further, in-vitro cytotoxicity, cellular uptake, and permeation of 12.5 and 25 μM QF-Nanoemulgel were assessed on RPMI-2650 cells and discovered nontoxic with 0.55 ± 0.02 µg and 1.1 ± 0.04 µg cellular permeation, respectively, which ensured the safety and potency of QF-Nanogel. Current research revealed the successful development of intranasal QF-Nanoemulgel as a novel dosage form for the safe and effective delivery of QF in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Quetiapine is an atypical antipsychotic prescribed for schizophrenia, bipolar disorder, multiple drug abuse (MDA), generalized anxiety disorder, severe depression, dementia, and mood disorders. Prescription of quetiapine varies according to use, with side effects increasingly reported with higher doses. Many previous case reports highlighted the misuse of the drug. Here we studied the prescribing patterns of quetiapine in multiple drug abuse (MDA), depression, and psychosis patients in the Madinah region in Saudi Arabia. This is a retrospective single-center study carried out in the main referral hospital for mental health in Madinah, Saudi Arabia for the period December 2020 till December 2021. A total of 158 patients were included in this study. The mean age of the patients was 30.5 ± 10.1 years. Male presented for 89.9 % of the patients. In terms of quetiapine indications, 46.2 % of patients used it for MDA, 29.7 % for psychosis, and 24.1 for depression. For all patients, quetiapine was used with a mean daily dose of 285.2 ± 222 mg and for a mean duration of 13.9 ± 15.4 weeks. Quetiapine was prescribed with a mean of 2.1 ± 2.2 prescriptions. Comparison between different indications shows that quetiapine was more frequently prescribed for MDA (p < 0.001). The MDA patients were significantly younger than in other groups (p = 0.001). All patients who received quetiapine for MDA were males. However, MDA patients received a smaller dose of quetiapine than other indications (p < 0.001). There were no significant differences between groups in terms of the number of prescriptions, duration, and whether the patient was on other medications or not. These results have been confirmed by regression analysis, where male and younger ages represented a significant contributing factor to MDA compared to psychosis, 95 % CI: 8 x107 (8 x107 − 8 x107) and 0.943 (0.900–––0.987), respectively. Quetiapine was prescribed more frequently in MDA patients and younger individuals. Low dose was predominant in those patients, indicating a probability of drug abuse. [ABSTRACT FROM AUTHOR]

• Quetiapine remarkably induced necroptosis. • CB1R antagonists or CB2R agonists inhibited necroptosis. • CB1R antagonists or CB2R agonists protected against quetiapine cardiotoxicity. Quetiapine is a common atypical antipsychotic used to treat mental disorders such as schizophrenia, bipolar disorder, and major depressive disorder. There has been increasing number of reports describing its cardiotoxicity. However, the molecular mechanisms underlying quetiapine-induced myocardial injury remain largely unknown. Herein, we reported a novel cell death type, quetiapine-induced necroptosis, which accounted for quetiapine cardiotoxicity in mice and proposed novel therapeutic strategies. Quetiapine-treated hearts showed inflammatory infiltration and evident fibrosis after 21-day continuous injection. The specific increases of protein levels of RIP3, MLKL and the phosphorylation of MLKL showed that quetiapine induced necroptotic cell death both in vivo and in vitro. Pharmacologic blockade of necroptosis using its specific inhibitor Necrostatin-1 attenuated quetiapine-induced myocardial injury in mice. In addition, quetiapine imbalanced the endocannabinoid system and caused opposing effects on two cannabinoid receptors (CB1R and CB2R). Specific antagonists of CB1R (AM 281, Rimonabant), but not its agonist ACEA significantly ameliorated the heart histopathology induced by chronic quetiapine exposure. By contrast, specific agonists of CB2R (JWH-133, AM 1241), but not its antagonist AM 630 exerted beneficial roles against quetiapine cardiotoxicity. The protective agents (AM 281, Rimonabant, AM 1241, and JWH-133) consistently inactivated the quetiapine-induced necroptosis signaling. Quetiapine bidirectionally regulates cannabinoid receptors and induces myocardial necroptosis, leading to cardiac toxic effects. Therefore, pharmacologic inhibition of CB1R or activation of CB2R represents promising therapeutic strategies against quetiapine-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

• There was no evidence of moderation in treatment response by cytokine variables. • Changes in depression scores were not significantly correlated with changes in cytokines. • The quetiapine treated group showed more pro-inflammatory changes. • Psychotherapy alone does not appear to confer added metabolic burdens in bipolar II disorder. • Treatments with low inflammatory burden such as psychotherapy may be important options in bipolar II disorder. Limited prospective data, mostly focused on bipolar I disorder, suggests that pro-inflammatory cytokines are elevated in abnormal mood states. We evaluated whether treatment normalizes peripheral markers of inflammation in bipolar II disorder. Using data from a randomized clinical trial of Interpersonal and Social Rhythm Therapy (IPSRT) + quetiapine vs. IPSRT + placebo for bipolar II depression, we examined whether these treatments for bipolar II depression impact inflammatory cytokines and whether observed changes in cytokines are associated with changes in depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD-17). Cytokine values were available for 33 participants who completed baseline and 20-week follow-up visits. After excluding those with CRP values > = 10 mg/L, there were 27 patients available for analysis (IPSRT + quetiapine N = 10, IPSRT + placebo N = 17). Baseline measure of inflammation did not appear to moderate treatment response, nor was change in HRSD-17 score correlated with changes in cytokines. Those who received IPSRT + quetiapine had significantly greater increases in IL-6 (p = 0.02) and TNF-α (p = 0.04), even after adjusting for changes in body mass index, than the IPSRT alone group. Descriptively, the quetiapine group showed increases in pro-inflammatory and decreases in anti-inflammatory cytokines and the psychotherapy group showed reduced pro-inflammatory cytokines. Despite both groups showing depression improvement, this small study suggests a more pro-inflammatory cytokine profile over time with quetiapine plus psychotherapy compared to psychotherapy alone. Elevated risk of cardiovascular morbidity and mortality among those with bipolar II disorder underscores the importance of delivering treatments that do not exacerbate these risk factors. [ABSTRACT FROM AUTHOR]

A rapid, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of 12 psychotropic drugs and metabolites in hair was developed and validated. After freeze grinding with methanol, the supernatant was determined by LC-MS/MS using an Allure PFPPropyl column (100 × 2.1 mm, 5 μm) with a gradient elution of acetonitrile and 10 mmol/L ammonium acetate with 0.1% formic acid, and in the subsequent analysis using multiple reaction monitoring (MRM) mode, two ion transitions were monitored for each analyte. The limits of detection ranged from 0.002 to 0.05 ng/mg, and the limits of quantitation were in the range of 0.005-0.1 ng/mg. Good linearity (r > 0.995) was observed for all analytes over the linear range. Acceptable intraday and interday precision (RSD ≤ 20%) and accuracy (85.3%-112.9%) were achieved. This method of detection was applied to the analysis of guinea pig hair roots after a single dose of quetiapine. Quetiapine and 7-hydroxyquetiapine were both detected in guinea pig hair roots from 5 min post administration. The concentration of quetiapine (10.3-1733.8 ng/mg) was much higher than that of 7-hydroxyquetiapine (0.1-40.6 ng/mg) in the hair roots of guinea pigs, and higher concentrations of quetiapine and 7-hydroxyquetiapine occurred in black hair root than in that of white and brown. The animal experiment demonstrated that hair roots may be a good specimen for proving acute quetiapine poisoning when other biological matrices are not available. [ABSTRACT FROM AUTHOR]

Antipsychotics have been shown to stimulate different forebrain areas, whereas some of them are sensitive to stress. In the present study, effect of a single administration of olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) on the activity of cells in the striatal dorsolateral (stDL) area, the periventricular zone (peVZ), the septal ventrolateral (seVL) nucleus, and the accumbens nucleus shell (shACC) and core (coACC) was investigated in male rats preconditioned with a mild stress complex (CMS) for 20 days. The objective of the study was to extend the anatomical-functional knowledge on the mechanism of selected antipsychotics with the goals: 1) to analyze the ability of the selected antipsychotics to induce c-Fos protein expression in the above mentioned forebrain structures and to map the pattern of their topography and 2) to find out whether longer-lasting mild stress preconditioning may modify the impact of the selected antipsychotics on the activity of cells in the forebrain areas in adult rats. Ten groups of rats were used. CMS complex contained five stressors: cage crowding, air-puff noising, wet bedding, predator stress, and forced swimming. AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg), and ARI (10 mg/kg/b.w.) were administered intraperitoneally and 90 min later the animals transcardially perfused by fixative. c-Fos was visualized by ABC complex. In unstressed animals, OLA and ARI elevated c-Fos expression in all areas studied, AMI and QUE in all areas except stDL, seVL and coACC, shACC FL-2 (shACC posterior level), respectively. CMS potentiated the effect of AMI in coACC, and QUE in shACC FL-2 and suppressed the effect of AMI in peVZ, and ARI in peVZ and seVL. The present data provide new insights into activity of cells in response to CMS challenge, which might be helpful in understanding the diverse clinical effects of atypical antipsychotics. • Olanzapine, amisulpride, aripiprazole, and quetiapine stimulated c-Fos expression in the rat striatum. • The anatomical profile of c-Fos expression induced by individual antipsychotics considerably differed. • Stress preconditioning in some cases potentiated or inhibited the acute effect of neuroleptics. [ABSTRACT FROM AUTHOR]

Background: Patients with methamphetamine (MA) abuse under methadone maintenance treatment (MMT) are susceptible to several complications including cognitive disturbance and mental health disorder. This trial was designed to determine the impacts of quetiapine administration on cognitive function and mental health scale in patients with MA abuse under MMT.Methods: This study was carried out in 60 MA abusers under MMT. Patients were randomly allocated to receive either 100 mg quetiapine (n = 30) or control (n = 30) daily for 8 weeks. Cognitive function and mental health scale were taken at baseline and post-treatment to evaluate relevant variables.Results: Quetiapine significantly decreased depression (b -3.94; 95% CI, -7.73, -0.16; P = 0.04) and sleep disorder (b -2.18; 95% CI, -2.89, -1.47; P < 0.001). Also, quetiapine administration resulted in a significant reduction in Iowa Gambling Task (b -2.70; 95% CI, -4.69, -0.71; P = 0.009), and significant increases in Verbal Fluency Test (b 3.04; 95% CI, 1.24, 4.85; P = 0.001), Reverse Digit Span (b 2.80; 95% CI, 2.13, 3.47; P = 0.001) compared with the placebo.Conclusion: Overall, taking 100 mg quetiapine daily for 8 weeks by patients MA abuse in MMT had favorable effects on some of cognitive functions and mental health parameters. [ABSTRACT FROM AUTHOR]

Abstract Previous studies suggest immunological alterations in patients with first-episode psychosis (FEP). Some studies show that antipsychotic compounds may cause immunomodulatory effects. To evaluate the immunological changes and the possible immunomodulatory effects in FEP, we recruited patients with FEP (n = 67) and matched controls (n = 38), aged 18–40 years, from the catchment area of the Helsinki University Hospital and the City of Helsinki, Finland. Fasting peripheral blood samples were collected between 8 and 10 a.m. in 10 ml PAXgene tubes. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 147 candidate genes reflecting activation of the immune system. Cases had higher gene expression levels of BDKRB1 and SPP1 / osteopontin compared with controls. Of the individual medications used as monotherapy, risperidone was associated with a statistically significant upregulation of 11 immune system genes, including cytokines and cytokine receptors (SPP1 , IL1R1 , IL1R2), pattern recognition molecules (TLR1 , TLR2 and TLR6 , dectin-1 / CLEC7A), molecules involved in apoptosis (FAS), and some other molecules with functions in immune activation (BDKRB1 , IGF1R , CR1). In conclusion, risperidone possessed strong immunomodulatory properties affecting mainly innate immune response in FEP patients, whereas the observed effects of quetiapine and olanzapine were only marginal. Our results further emphasize the importance of understanding the immunomodulatory mechanisms of antipsychotic treatment, especially in terms of specific compounds, doses and duration of medication in patients with severe mental illness. Future studies should evaluate the response pre- and post-treatment, and the possible role of this inflammatory activation for the progression of psychiatric and metabolic symptoms. Highlights • Expression of BDKRB1 and osteopontin/SPP1 was higher in FEP patients than in controls. • Risperidone use was associated with a robust upregulation of immune system genes. • Observed effects of quetiapine and olanzapine use were only marginal. [ABSTRACT FROM AUTHOR]

Highlights • Regional differences in hippocampal neurogenesis (NG) were assessed in male rats. • Chronic quetiapine (QTP) treatment exclusively stimulated dorsal hippocampal NG. • QTP did not block the social defeat-induced decrease in NG of ventral hippocampus. • Stress-induced hyponeophagia was not reversed by chronic administration of QTP. Abstract Quetiapine, an atypical antipsychotic, has been used for the treatment of several neuropsychiatric disorders. However, the underlying mechanism of the broad therapeutic range of quetiapine remains unknown. We previously reported that several aversive conditions affect dorsal/ventral hippocampal neurogenesis differentially. This study was aimed to elucidate the positive effects of chronic treatment with quetiapine on regional differences in hippocampal proliferation and immature neurons and behavioral changes under psychosocial stress using the Resident-Intruder paradigm. Twenty-three male Sprague-Dawley rats were intraperitoneally administered a vehicle or quetiapine (10 mg/kg) once daily for 28 days. Two weeks after starting the injections, animals were exposed to intermittent social defeat (four times over two weeks). The behavioral effects of stress and quetiapine were evaluated by the Novelty-Suppressed Feeding (NSF) test. The stereological quantification of hippocampal neurogenesis was estimated using immunostaining with Ki-67 and doublecortin (DCX). Chronic quetiapine treatment stimulated the Ki-67- and DCX-positive cells in the dorsal hippocampus, but not in the ventral subregion. The stress-induced changes in neurogenesis and hyponeophagic behavior were not reversed by repeated administration of quetiapine. Future study with additional behavioral tests is needed to elucidate the functional significance of the quetiapine-induced increase in dorsal hippocampal neurogenesis. [ABSTRACT FROM AUTHOR]