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In this case report, we present a 57-year-old woman, experiencing worsening attention and concentration in the past month. She had paranoid and persecutory delusions regarding her husband. In the initial evaluation, her cardiac and liver enzymes were found to be elevated, and her blood pressure was high. She was taking antihypertensives, antidepressants, and disulfiram for the treatment of her addiction to alcohol. Her initial neurological examination was nonspecific. Mental status examination revealed distractible attention, psychomotor agitation, and poor insight. A cranial MRI revealed signal intensity changes suggestive of vasogenic edema in bilateral hemispheres and the basal ganglia. The atypical presentation of Posterior Reversible Encephalopathy Syndrome (PRES) was diagnosed. The encephalopathy presentation and peripheral toxic symptomatology were resolved following hydration and antihypertensive medication; yet, during the follow-up of the patient, motor deficits in the lower extremity were noted. An EMG examination indicated motor polyneuropathy with axonal involvement. As her muscular weakness increased, IVIG was initiated, and the symptoms of polyneuropathy improved rapidly. The multisystemic pathologies developed in a short time were indicative of potential toxicity, while other infectious, autoimmune, infiltrative, and metabolic etiology were excluded upon laboratory tests and imaging. The use of disulfiram was thought to be a key element in the development of this chain of pathologies. Based on our knowledge, this is the first case to be reported in which the cardiovascular, hepatic, muscular, central, and peripheral nervous system toxicity of disulfiram was observed simultaneously, which is the reason why we consider it important to be presented. [ABSTRACT FROM AUTHOR]

The current quasi-experimental study explored the effects of Baduanjin qigong on body mass index (BMI) and five metabolic indexes in people with schizophrenia. Inclusion criteria were body mass index >25 kg/m2 or metabolic syndrome. Twenty-two service users were recruited from a psychiatric center and were assigned to the experimental group (EG) or control group (CG) using blocked randomization. The EG performed Baduanjin qigong lasting 1 hour for 12 weeks three times per week, whereas the CG received routine care. Generalized estimating equations showed that the EG achieved a greater decrease in BMI and waist circumference (WC) than the CG post-intervention. Baduanjin qigong may provide an effective nonpharmacological approach to reducing BMI and WC in people with schizophrenia. This study showed that performing Baduanjin qigong for 12 weeks is a feasible and effective strategy for improving the body shape of individuals with chronic schizophrenia, thus providing results that can serve as a reference for health professionals working in psychiatry departments. [Journal of Psychosocial Nursing and Mental Health Services, 62(4), 41–48.] [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]

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Opioids or benzodiazepines use is known to increase the risk of delirium. The prevalence of delirium is high in pediatric cardiac intensive care units (CICUs) with associated morbidity and mortality. We investigate the short-term effects of quetiapine, an atypical antipsychotic medication, on opioid and benzodiazepine requirements, and any associated adverse events as we utilize quetiapine to treat delirium symptoms in this single-center, retrospective study. Twenty-eight patients who received quetiapine between January 2018 and June 2019 in the CICU met inclusion criteria for the analysis. The quetiapine initiation dose was 0.5 mg/kg/dose every 8 h and we allowed 48 h for quetiapine to reach a steady state. Overall opioid and benzodiazepine requirements were compared 72 h before and 72 h after the quetiapine steady state. There was a statistically significant reduction in the total daily opioid (p = 0.001) and benzodiazepine (p = 0.01) amounts following quetiapine initiation. There was also a statistically significant decrease in the total number of daily PRNs requirement for both opioids (p < 0.001) and benzodiazepines (p = 0.03). Nine out of 13 patients were completely weaned off continuous opioid drips following quetiapine initiation (p = 0.01). The presence of steady-state habituation medications, including methadone or lorazepam, did not have any statistically significant effect on weaning continuous opioid (p = 0.18) or benzodiazepine (p = 0.62) drips. There was no statistically significant effect of quetiapine on the QTc interval after quetiapine initiation (p = 0.58) with no clinically significant arrhythmias observed during the study period. Our study demonstrates a statistically significant reduction in opioid and benzodiazepine requirements following quetiapine initiation to treat delirium symptoms without significant adverse effects in patients with congenital heart disease in the short term. [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]

In 2023, we observed the sixtieth anniversary of the article by a British psychiatrist, Geoffrey Hartigan, demonstrating, for the first time, the possibility of preventing the recurrence of mood disorders by using lithium salts. Herein, a history of prevention of recurrences of mood disorders both worldwide and in Poland will be presented concerning both lithium and other mood-stabilizing drugs. The merit for verifying the prophylactic lithium effect in the 1960-1970s should be given to Danish researchers, Mogens Schou and Poul Baastrup. In Poland, the first paper on prophylactic lithium appeared already in 1971. In the 1970s, French researchers showed prophylactic activity of valproic acid amide, and Japanese researchers - of carbamazepine. In the 1980s, studies on valproic acid amide were performed in the 2nd Psychiatric Clinic of the Institute of Psychiatry and Neurology led by Prof. Pużyński. Since the mid-1990s, 2nd generation mood-stabilizing drugs have been introduced, including some atypical antipsychotics (clozapine, olanzapine, quetiapine, aripiprazole, risperidone) and an anticonvulsant drug, lamotrigine, showing prophylactic activity in bipolar mood disorder. The studies on lithium resulted in the identification of factors connected with its prophylactic efficacy as well as the antisuicidal, antiviral, and neuroprotective effects of this drug. From a sixty-year perspective following Hartigan's article, it seems that his pioneering concept on the possibility of pharmacological influence on the course of mood disorders was fully confirmed. Current Polish recommendations on pharmacological prophylaxis of mood disorders were presented in the books Standardy leczenia niektórych zaburzeń psychicznych and Psychofarmakologia kliniczna, both published in 2022. [ABSTRACT FROM AUTHOR]

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Introduction: Type 1 diabetes mellitus is characterized by an absolute insulin deficiency requiring the lifetime intensive insulin therapy accompanied by daily self-monitoring, self-management, ongoing education, and complex diabetes care. Regular patient-clinician shared therapeutic decisions based on age, sex, comorbidities, medications, predicted impact of meals, physical activity, stress, hormonal changes, insulin therapy, and patterns of glycemic changes are key for achieving glycemic targets. The impact of various phases of bipolar disorder and their treatment on continuous glucose levels remains unexplored and calls for future assessments. Case presentation: The present case reports a 41-year-old Caucasian female with an established diagnosis of bipolar II disorder and type 1 diabetes mellitus who discontinued long-term mood-stabilizing pharmacotherapy with quetiapine. Real-time continuous glucose monitoring performed before and 6-months following the discontinuation of quetiapine revealed hidden glucose patterns in medicated versus unmedicated bipolar disorder. Despite the known adverse metabolic effects of quetiapine, the continuous glucose monitoring captured more stable and near-normal continuous glucose values during the antipsychotic treatment compared to unmedicated stages of bipolar disorder with considerably higher glucose values and glucose variability. Conclusion: The case report highlights the importance of the ongoing psychopharmacotherapy of bipolar disorder in comorbid type 1 diabetes mellitus to reduce mood-induced reactivity, emotional urgency, and nonemotional impulsivity that may contribute to dysglycemia. If not effectively treated, the "bipolar diabetes" is likely to progress to multiple psychiatric and somatic complications. The bidirectional links between the phases of bipolar disorder and the corresponding continuous glucose patterns can help advance clinical decision-making and yield innovative1 research that can translate into efficacious clinical practice. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post‐treatment thyroid function between the two therapies. Methods: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid‐stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. Results: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one‐month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one‐month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one‐month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). Conclusion: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid. [ABSTRACT FROM AUTHOR]

Psychotic symptoms in people with Parkinson's disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of 'minor' hallucinations. This article focuses both on the phenomenology of psychotic symptoms and their management. Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches. Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. 'Minor hallucinations' rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail. [ABSTRACT FROM AUTHOR]

Background: The neuroinflammatory hypothesis of Major Depressive Disorder (MDD) postulates that dysregulated cytokine production is implicated in the etiopathology of the disorder. This study aimed to determine baseline levels of Interleukin-8 (IL-8), an inflammatory cytokine, in MDD and identify possible changes in response to antidepressant drug therapy. Methods: Two independent groups of MDD patients who met study criteria were enrolled; one group was treated with Escitalopram and the other with Quetiapine for twelve weeks. There was a healthy control (HC) group. In the Escitalopram group 30 patients completed the baseline visit and in the Quetiapine group 43 patients. Plasma concentrations of IL-8 were measured at baseline, week eight, and week 12 of treatment. IL-8 levels were correlated with depression severity at baseline and week 12. The sample size for IL-8 analysis was 17 study completers in the Escitalopram study, 21 study completers in the Quetiapine study, and 19 HCs. We used the Student's t-test and the Pearson Correlation Coefficient for statistical analyses. Results: MDD patients exhibited elevated IL-8 levels at baseline compared to healthy controls (p = 0.007). However, IL-8 levels did not show a significant reduction after 12 weeks of treatment and were not significantly correlated with depression severity at either baseline or week 12 of treatment. However, there was a notable downtrend in IL-8 levels after treatment in both groups though not statistically significant. Limitations: Study limitations include sample size variations and power, and study length. No formal assessment was conducted to rule out Axis II diagnoses. Conclusions: These findings underscore the relationship between IL-8 and MDD, suggesting that IL-8 may play a role in the pathophysiology of MDD, but its relationship with antidepressant treatment requires a prolonged period of treatment. This study suggests a role for IL-8 in MDD as a pro-inflammatory biomarker, while the lack of immediate normalization post-treatment indicates the need for further exploration of delayed effects of antidepressant therapy on immune markers and IL-8′s relationship with the mechanism of action of specific pharmacotherapies used in MDD.

Background: Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits. Aim: To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies. Methods: A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI–qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined. Results: A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination. Conclusion: The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.

Aim: Real-world healthcare resource use (HCRU) burden among patients with Parkinson’s disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (other-AAPs) including quetiapine (QUE) in long term care (LTC) and nursing home (NH) settings are lacking. This analysis examines HCRU differences among residents in LTC/NH settings who initiate PIM versus QUE or other-AAPs. Methods: A retrospective analysis of LTC/NH residents with PDP from the 100% Medicare claims between 1 April 2015 and 31 December 2021 was conducted. Treatment-naive residents who initiated ≥6 months continuous monotherapy with PIM or QUE or other-AAPs between 04/01/16 and 06/30/2021 were propensity score matched (PSM) 1:1 using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Post-index (i.e., 6 months) HCRU outcomes included: proportion of residents with ≥1 all-cause inpatient (IP) hospitalizations and emergency room (ER) visits. HCRU differences were assessed via log binomial regression and reported as relative risk ratios (RR) and 95% confidence intervals after controlling for dementia, insomnia and index year. Results: From a total of PIM (n = 1827), QUE (n = 7770) or other-AAPs (n = 9557), 1:1 matched sample (n = 1827) in each cohort were selected. All-cause IP hospitalizations (PIM [29.8%]) versus QUE [36.7%]) and ER visits (PIM [47.3%] versus QUE [55.8%]), respectively, were significantly lower for PIM. PIM versus QUE cohort also had significantly lower RR for all cause IP hospitalizations and ER visits, respectively, (IP hospitalizations RR: 0.82 [0.75. 0.9]; ER visits RR: 0.85 [0.8. 0.9]). PIM versus other-AAPs also had lower likelihood of HCRU outcomes. Conclusion: In this analysis, LTC/NH residents on PIM monotherapy (versus QUE) had a lower likelihood of all-cause hospitalizations (18%) and ER (15%) visits. In this setting, PIM also had lower likelihood of all-cause HCRU versus other-AAPs.

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.

Abstract Background Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. Methods The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. Results Four predictors were selected from 38 variables by the univariate analysis (p

The article discusses the use of long-term repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD), highlighting two case studies of patients who maintained remission through extended rTMS therapy. Topics discussed include the effectiveness of maintenance rTMS, individualized treatment protocols, and the impact of comorbid conditions on therapy outcomes.

The polymorphism of the clinical manifestations of schizophrenia and bipolar affective disorder (BD), late referral to the doctor, comorbidity with somatic diseases and the use of somatotropic medications by psychiatric patients, as well as the frequent development of adverse events (AEs), require constant analysis and improvement of the methods and means of psychopharmacotherapy.Objective: to study the characteristics of the use of quetiapine (Seroquel®) in real outpatient clinical practice.Material and methods. A patient was enrolled in the program if there was a need to prescribe quetiapine (Seroquel®) or to switch from the current therapy to quetiapine. During the program visit, the doctor filled in an individual registration card with information about patient and therapy. The data were statistically analyzed.Results. Quetiapine is prescribed by practicing psychiatrists in Russia not only according to the official indications, but also for psychopathological disorders of other nosology with similar clinical manifestations, such as dementia, organic and affective (depressive episode, recurrent depressive disorder), as well as psychogenic disorders. Up to 27.3% of physicians consider the effect of quetiapine to be quite sufficient in a mixed affective state within the framework of BD dynamics. Quetiapine is used by physicians to treat patients with varying duration of mental disorder (mean 5.1–13.5 years), severity of current mental state (mean CGI-S score 4.3–4.97) and a wide age range (mean age 34.5–60.8 years). When prescribing quetiapine, physicians note that the drug has antidepressant, anxiolytic, sedative and hypnotic effects, regardless of the type of mental disorder. Quetiapine is mainly prescribed as a monotherapy, either primary or resumed after a break – 815 (64.5%) observations. At the same time, quetiapine is used significantly more frequently as monotherapy for BD (69.4%) and mental illnesses of other origin (64.7%) than for schizophrenia (53.8%; p

Hy D Nguyen,1 Hai V Ngo,1 Van Hong Nguyen,2 Myung-Chul Gil,1,3 Beom-Jin Lee1,4 1College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea; 2Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, 10000, Vietnam; 3PLUTO Inc, Seongnam, 13453, Republic of Korea; 4Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, 16499, Republic of KoreaCorrespondence: Beom-Jin Lee, College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea, Tel +82 31 219 3442, 3430, Fax +82 31 212 3653, Email bjl@ajou.ac.krBackground: Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low bioavailability and physicochemical/biopharmaceutical issues.Purpose: To investigate the roles of fatty acid chain length and enzyme-oriented QTP controlled release from pH-triggering self-assembled fatty acid conjugated QTP nanosuspensions (NSPs).Methods: QTP was conjugated with different chain length fatty acids (C10–decanoic acid, C14–myristic acid, C18–stearic acid) to obtain QTP-fatty acid conjugates (QFCs: QD, QM, QS) by exploiting 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/4-dimethylaminopyridine (EDC/DMAP) conjugation chemistry. Then, the solubility, partitioning coefficient (log P), cell viability and cleavage kinetics of QFCs were evaluated. The pH-triggering self-assembled behaviors of QFCs to form QTP-fatty acid NSPs (QDN, QMN, QSN) by varying pH, QFC concentration and proton-to-QTP ratios were characterized. The morphological images, critical micelle concentration (CMC), physicochemical properties and enzyme-oriented QTP controlled release of NSPs were examined.Results: Three QFCs were synthesized with different chain length fatty acids from QTP after desalting fumarate from QTP fumarate. The pH, QFC concentration and proton-to-quetiapine molar ratio could influence physicochemical properties and nanonization behaviors of QFCs. All three QFCs showed no effect on the viability of myoblast cells. The pH-triggering self-assembly of amphiphilic QFCs to form nanoparticles (NPs) occurred as the amine moiety of QTP was readily ionized in a strongly acidic environment (pH 1.2). Interestingly, the longer the fatty acid chain length, the lower water solubility, the higher log P (lipophilicity) and the smaller NP particle size were observed. The conversion rate of QFCs to liberate QTP by esterase in human plasma and liver S9 fractions was also inversely proportional to the fatty acid carbon chain length. Interestingly, the freeze-dried QMN showed the esterase-oriented controlled release of QTP over one month, unlike the initial burst release of QDN or the slowly delayed release pattern of QSN.Conclusion: A new pH-triggering self-assembled nanonization platform was developed using different chain length fatty acid conjugated QTP in low pH environment. By varying fatty acid chain length, the enzyme-oriented QTP controlled release dosage form was challenged to enhance the therapeutic effectiveness of QTP. Keywords: quetiapine, fatty acid conjugated quetiapine, fatty acid chain length, fattigation platform, nanonization, pH-triggering self-assembly, enzyme-oriented controlled release, nanosuspension

The behavioural variant of Frontotemporal Dementia (bvFTD) is a neurodegenerative condition characterized by behavioural and cognitive symptoms. Mood disturbances, including manic-like episodes, can occur in bvFTD, posing diagnostic and therapeutic challenges. This case report presents a 62-year-old male with bvFTD exhibiting weekly mood fluctuations alternating between manic and depressive-like states. While initial treatment with quetiapine and trazodone showed partial improvement, the periodicity of mood fluctuations persisted. Subsequently, lithium was introduced, resulting in a notable reduction in symptom severity for both manic and depressive episodes. This report highlights the potential use of lithium as a mood stabilizer in bvFTD patients with periodic mood fluctuations, refractory to standard treatments. Further research is needed to elucidate the mechanisms underlying lithium's efficacy in bvFTD and to establish treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. Objective: The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan. Methods: Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. Results: We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. Conclusions: We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose. [ABSTRACT FROM AUTHOR]

Background: Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. Methods: The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. Results: Four predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively. Conclusions: In this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations. [ABSTRACT FROM AUTHOR]

Introduction: according to the definition of the World Health Organization, addiction is a chronic, relapsing, long-term disease primarily of the brain and central nervous system, which leads to the need for continuous and further intake of the substance. The most common psychiatric comorbidities among psychoactive substances addicts are mood disorders, anxiety disorders and personality disorders. Quetiapine, atypical antipsychotic, is commonly used in treatment of addiction nowadays. Aim: to evaluate the difference between patien ts treated with quetiapine who only had a diagnosis of addiction and those who have a dual diagnosis in relation to quetiapine dosage, as well as to evaluate the difference between patients in relati on to arbitrarily dropout from treatment. Materials and methods: the research was cross-sectional and included a review of the medical histories of 68 patients aged 21-64 with confirmed addiction hospitalized at the Institute for Addiction Diseases of Canton Sarajevo in the period from January to December 2023, and who were treated with quetiapine during hospital treatment, classified into two groups. Results: the largest number of patients used quetiapine in a single dose and in the evening, without a significant difference between the groups (p>0.05). Patients diagnose only with addiction more often voluntarily left treatment in 31.0 cases compared to 15.4% of patients with multiple diagnosis, but without statistically significant difference between the groups. Conclusion: quetiapine was used in same dosage in treatment of subjects with only addiction as well as subjects with dual diagnosis. Patients who were diagnosed only with addiction voluntarily left treatment more often compared to patients with dual diagnoses. [ABSTRACT FROM AUTHOR]

Changes in pharmacokinetics and endogenous metabolites may underlie additive biological effects of concomitant use of antipsychotics and opioids. In this study, we employed untargeted metabolomics analysis and targeted analysis to examine the changes in drug metabolites and endogenous metabolites in the prefrontal cortex (PFC), midbrain, and blood of rats following acute co-administration of quetiapine and methadone. Rats were divided into four groups and received cumulative increasing doses of quetiapine (QTP), methadone (MTD), quetiapine + methadone (QTP + MTD), or vehicle (control). All samples were analyzed using liquid chromatography-mass spectrometry (LC–MS). Our findings revealed increased levels of the quetiapine metabolites: Norquetiapine, O-dealkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide, in the blood and brain when methadone was present. Our study also demonstrated a decrease in methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in the rat brain when quetiapine was present. Despite these findings, there were only small differences in the levels of 225–296 measured endogenous metabolites due to co-administration compared to single administrations. For example, N-methylglutamic acid, glutaric acid, p-hydroxyphenyllactic acid, and corticosterone levels were significantly decreased in the brain of rats treated with both compounds. Accumulation of serotonin in the midbrain was additionally observed in the MTD group, but not in the QTP + MTD group. In conclusion, this study in rats suggests a few but important additive metabolic effects when quetiapine and methadone are co-administered. [ABSTRACT FROM AUTHOR]

Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, it is being encountered in medicolegal autopsies more frequently. For instance, it has been linked to increased mortality rates, most likely due to its adverse effects on the cardiovascular system. Its pharmacokinetic features and significant postmortem redistribution challenge traditional sampling in forensic toxicology. Therefore, a systematic literature review was performed, inclusive of PubMed, the Web of Science—core collection, and the Scopus databases; articles were screened for the terms "quetiapine", "death", and "autopsy" to reevaluate each matrix used as a surrogate endpoint in the forensic toxicology of quetiapine-related deaths. Ultimately, this review considers the results of five studies that were well presented (more than two matrices, data available for all analyses, for instance). The highest quetiapine concentrations were usually measured in the liver tissue. As interpreted by their authors, the results of the considered studies showed a strong correlation between some matrices, but, unfortunately, the studies presented models with poor goodness of fit. The distribution of quetiapine in distinct body compartments/tissues showed no statistically significant relationship with the length of the postmortem interval. Furthermore, this study did not confirm the anecdotal correlation of peripheral blood concentrations with skeletal muscle concentrations. Otherwise, there was no consistency regarding selecting an endpoint for analysis. [ABSTRACT FROM AUTHOR]

Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing. We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates. Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D2 receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain. Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal. CRD42023446654 [ABSTRACT FROM AUTHOR]

Aims: To investigate the effect of aging, sex and cytochrome P450 (CYP) genotypes on the exposure of quetiapine (QUE) and the pharmacologically active metabolite N‐desalkylquetiapine (NDQ). Methods: Patients with serum concentrations of QUE and NDQ were included retrospectively from a therapeutic drug monitoring service. The outcome measures were concentration:dose (C:D) ratios of QUE and NDQ, and NDQ:QUE metabolic ratio. Linear mixed model analyses were used to evaluate the effects of age, sex and, subsequently, CYP2D6/3A genotypes. Results: The average age of the included population (n = 8118 patients) was 44 years (13.5% ≥65 years). The C:D ratio of QUE and NDQ gradually increased in patients aged >50 years compared to those aged 18–30 years, with 28 and 29% increase, respectively, for patients aged >70 years (P <.001). Compared to males, females had 15% lower QUE C:D ratio and 10% higher C:D ratio of NDQ (both P <.001). The NDQ:QUE metabolic ratio was 30% higher in females than in males (P <.001). For females ≥65 years, the NDQ C:D ratio was 36% higher compared to males <65 years (P <.001). A significantly higher NDQ C:D ratio was observed for CYP2D6 intermediate (+7%, P =.012) and poor (+17%, P =.001) compared to normal metabolizers. No effects of CYP3A4*22 and CYP3A5*1 allele variants were observed. Conclusion: This study shows an increase of the QUE and NDQ exposures during aging. Old age, female sex and CYP2D6 allele variants encoding reduced activity are factors associated with high NDQ exposure. Therefore, females ≥65 years carrying CYP2D6 allele variants encoding reduced activity have the highest risk of dose‐dependent side effects of NDQ during QUE treatment. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the epidemiology of potential drug interactions in terminally-ill cancer patients receiving exclusively supportive care. In this cross-sectional study, during a 6-month follow-up, we considered the medical record of terminally-ill cancer patients referred to palliative care at the cancer center in Isfahan, Iran. Potential drug-drug interactions (DDIs) were assessed by Lexi-Interact ver.1.1 online software. During the study period, 133 terminally-ill cancer patients were recruited. We detected 1678 DDIs with moderate or major severity levels. Among them, 330, 219, 32, 1075, and 51 interactions were categorized in B, C, D, and X drug interactions categories, respectively. One hundred and twenty-two patients (91.73%) encountered at least one potential drug-drug interaction during the end of life care. Mechanistically, most drug-drug interactions (64.5%) were pharmacodynamics. The most frequent pharmacological class of drugs responsible for DDIs were quetiapine (91 cases), oxycodone (87 cases), and sertraline (55 cases). Interaction between oxycodone and sertraline was found to be in the top 10 detected DDIs (13.7%). Our results showed that potentially moderate or major drug-drug interactions often occur among terminally-ill cancer patients and the clinical significance of DDIs should be considered meticulously in the palliative care cancer setting. [ABSTRACT FROM AUTHOR]

Off-label prescribing refers to prescribing that is not concordant with the indications, doses, routes of administration or patient groups included in the Australian approved product information. Off-label prescribing is common, especially for vulnerable patient groups who tend to be excluded from clinical trials, such as children and pregnant women. There may be increased risk of prescriber liability if the patient experiences an adverse event following off-label prescription, particularly when supporting evidence or guidelines are lacking. There may be additional costs to the patient if the medicine is not subsidised for the off-label indication. Prescribers should ensure patients are aware when a medicine is being prescribed off label, and informed of potential benefits and harms. Alternative pathways for approval of new indications, doses and patient groups may reduce the need for off-label prescribing. [ABSTRACT FROM AUTHOR]

Purpose: Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM). Methods: This was a retrospective observational study involving a nested case–control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment. Results: The numbers of patients with non‐serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03–2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16–2.66). Conclusion: Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage. [ABSTRACT FROM AUTHOR]

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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]

Aims: There are increasing concerns about harms related to suboptimal antipsychotic use. Here we describe recent population‐based trends in antipsychotic use and harms in Australia and identify population groups exhibiting patterns of use likely to contribute to these harms. Methods: Using population‐based data from the Australian Pharmaceutical Benefits Scheme (2015‐2020), poisoning calls to the New South Wales (NSW) Poisons Information Centre (2015‐2020) and poisoning deaths in all coronial records (2005‐2018) in Australia, we measured trends in the prevalence of antipsychotic use and related deaths and poisonings. We applied latent class analyses to identify patterns of antipsychotic use that may contribute to harms. Results: Quetiapine and olanzapine had the highest prevalence of use between 2015 and 2020. Noteworthy trends included increases of 9.1% and 30.8% in quetiapine use and poisonings, while olanzapine use decreased by 4.5% but poisonings increased by 32.7%. Quetiapine and olanzapine poisonings and related deaths had the highest rates of co‐ingestion of opioids, benzodiazepines and pregabalin compared to other antipsychotics. We identified six distinct population groups using antipsychotics: (i) ongoing high‐dose use with sedatives (8%), (ii) ongoing use (42%), (iii) ongoing use with analgesics and sedatives (11%), (iv) long‐term low‐dose use (9%), (v) sporadic use (20%) and (vi) sporadic use with analgesics (10%). Conclusion: Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for example through prescription monitoring systems. [ABSTRACT FROM AUTHOR]

To investigate FDA-approved drugs prescribed for unrelated diseases or conditions that promote remission in subjects diagnosed with opioid use disorder (OUD). This was a retrospective observational study utilizing the TriNetX electronic medical record data. Subjects between 18 and 65 years old were included in this study. First, a drug screen was employed to identify medications used for chronic illness that are associated with OUD remission. Based on Fisher's exact test for significance, 28 of 101 medications were selected for further analysis. Positive (buprenorphine/methadone) and negative controls (benazepril) were included in the analysis. Medications were analyzed in the absence and presence of buprenorphine or methadone, two medications used to treat OUD, to identify the likelihood of OUD remission up to one year following the index event. We identify 8 medications (prazosin, propranolol, lithium carbonate, olanzapine, quetiapine, bupropion, citalopram, and escitalopram) that may be useful for increasing remission in OUD in the absence of buprenorphine or methadone. Additionally, our results identify psychiatric medications that when taken alongside buprenorphine and methadone improve remission rates. These results provide medication options that may be useful in treating OUD as well as integrated therapies to treat comorbid mental illness. [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]

A selective and sensitive new reversed-phase method was developed and validated by using Waters Acquity UHPLC system coupled with Waters Micromass Quattro PremierXE (MS/MS) to identify and quantify the genotoxic impurity 2-(2-chloroethoxy) ethanol at trace level (∼2.0 ppm) in quetiapine fumarate. The method used positive ion electrospray ionization with a multiple reaction monitoring detection mode using ACE3 C18(100 mm × 4.6 mm × 3.0 µm) column. For analysis, an isocratic program was developed using 0.01 M ammonium acetate in Milli-Q water (mobile phase A) and methanol (mobile phase B) in 20:80v/v ratio. Elution of 2-(2-chloroethoxy) ethanol was monitored using triple quadrupole mass spectrometer with an injection volume of 10 μl, a column oven temperature of 40 °C, an auto-sampler temperature of 15 °C, and flow rate of 0.5 mL/min. The retention time of 2-(2-chloroethoxy) ethanol was observed at 2.38 min. The LOQ and LOD were determined at concentrations of 0.235 ppm and 0.070 ppm respectively. The correlation coefficient R2 was 0.9983 and the percent recoveries of method range from 98.1% to 114.0%. The method was successfully validated according to International Council for Harmonization requirements (ICH Q2(R1) and ICH M7(R1)) for genotoxic impurities. The method was sensitive, selective, accurate and precise and therefore can be used for identification and quantification of genotoxic impurity 2-(2-chloroethoxy) ethanol in quetiapine fumarate. [ABSTRACT FROM AUTHOR]

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin–norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic–clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient's clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy. [ABSTRACT FROM AUTHOR]

IntroductionType 1 diabetes mellitus is characterized by an absolute insulin deficiency requiring the lifetime intensive insulin therapy accompanied by daily self-monitoring, self-management, ongoing education, and complex diabetes care. Regular patient-clinician shared therapeutic decisions based on age, sex, comorbidities, medications, predicted impact of meals, physical activity, stress, hormonal changes, insulin therapy, and patterns of glycemic changes are key for achieving glycemic targets. The impact of various phases of bipolar disorder and their treatment on continuous glucose levels remains unexplored and calls for future assessments.Case presentationThe present case reports a 41-year-old Caucasian female with an established diagnosis of bipolar II disorder and type 1 diabetes mellitus who discontinued long-term mood-stabilizing pharmacotherapy with quetiapine. Real-time continuous glucose monitoring performed before and 6-months following the discontinuation of quetiapine revealed hidden glucose patterns in medicated versus unmedicated bipolar disorder. Despite the known adverse metabolic effects of quetiapine, the continuous glucose monitoring captured more stable and near-normal continuous glucose values during the antipsychotic treatment compared to unmedicated stages of bipolar disorder with considerably higher glucose values and glucose variability.ConclusionThe case report highlights the importance of the ongoing psychopharmacotherapy of bipolar disorder in comorbid type 1 diabetes mellitus to reduce mood-induced reactivity, emotional urgency, and non-emotional impulsivity that may contribute to dysglycemia. If not effectively treated, the “bipolar diabetes” is likely to progress to multiple psychiatric and somatic complications. The bidirectional links between the phases of bipolar disorder and the corresponding continuous glucose patterns can help advance clinical decision-making and yield innovative1 research that can translate into efficacious clinical practice.

Objective: We aimed to investigate the risk of antipsychotic drug treatment in the development of metabolic syndrome (MetS) in children and adolescents and to determine which psychiatric disorder is more associated with MetS in the pediatric population. Methods: The sample consisted of 118 children and adolescents (88 used psychotropic medication). The hemogram, fasting blood glucose, lipid profile, weight, and blood pressure levels of all the participants and information regarding medication doses of the patient group at the sixth month of the treatment process were obtained. Results: Bipolar disorder (BPD) was the only psychiatric disorder associated with MetS. Quetiapine and valproic acid were found to have increasing effects on MetS. Weight gain and the increase in systolic and diastolic blood pressure significantly increased the likelihood of MetS. Hierarchical logistic regression analyses revealed that quetiapine increased the risk of MetS through weight gain, and valproic acid increased MetS risk through systolic blood pressure. Conclusion: Especially BPD and psychotropic use in children and adolescents disrupt metabolic regulation and pose a risk for MetS. Determining the risk factors causing MetS, especially in children and adolescents, plays a significant role in preventing mortality and morbidity at advanced ages.

Objective(s): Lithium and quetiapine are administered simultaneously as a treatment for bipolar disorder. The concurrent use of these two drugs has been observed to affect the neurobiological mechanisms underlying learning and memory. To clarify the precise mechanisms involved, we evaluated the possible role of the dorsal hippocampal CA1 NMDA receptors in the interactive effects of lithium and quetiapine in memory consolidation. Materials and Methods: The dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated, and a single-trial step-through inhibitory avoidance apparatus was used to assess memory consolidation. Results: Post-training administration of certain doses of lithium (20, 30, and 40 mg/kg, IP) diminished memory consolidation. Post-training administration of higher doses of quetiapine (5, 10, and 20 mg/kg, IP) augmented memory consolidation. Post-training administration of certain doses of quetiapine (2.5, 5, 10, and 20 mg/kg) dose-dependently restored lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10-5 and 10-4 µg/rat, intra-CA1) plus an ineffective dose of quetiapine (2.5 mg/kg) restored the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-801 (0.0625 and 0.0125 μg/rat, intra-CA1), diminished the quetiapine-induced (10 mg/kg) memory improvement in lithium-induced memory impairment.Conclusion: These findings suggest a functional interaction between lithium and quetiapine through hippocampal CA1 NMDA receptor mechanisms in memory consolidation.

Objective To investigate the efficacy and effects on cognitive function and sleep quality of Buqi Wenyang Dingkuang Decoction in treatment of mania patients with upfloating of asthenia yang type. Methods A total of 100 patients with mania who were hospitalized between January 2020 and January 2022 in the Affiliated Brain Hospital of Guangzhou Medical University were selected and divided into observation group and control group according to the random number table method (n=50, each) . Both group was given valproate sustained-release tablets and quetiapine tablets treatment, and the observation group was added with Buqi Wenyang Dingkuang Decoction. The treatment course of the 2 groups was 4 weeks. Treatment efficacy and incidence of adverse reactions were compared between two groups. The primary syndrome score, Clinical Global Impressions Scale (CGI) score, Pittsburgh Sleep Quality Index (PSQI) score and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score before and after treatment were compared between the two groups. Results The total effective rate was higher in the observation group than in the control group (90.00% vs 72.00%, χ2=5.263, P＜0.05) . The scores of mania, thirst not to drink, and limb cold at 4 weeks of treatment in the 2 groups were lower than those before treatment (P＜0.05) , and those of the observation group were lower than those of the control group (P＜0.01) . The BRMS scale score, CGI score, and PSQI scale score of the 2 groups at 4 weeks of treatment were lower than those before treatment (P＜0.01) , and the above-mentioned scores of the observation group were lower than those of the control group (P＜0.01) . The scores of immediate memory, spatial structure, attention, verbal function, and delayed memory in the 2 groups at 4 weeks of treatment were higher than those at pretreatment (P＜0.01) , and the scores in the observation group after treatment were higher than those in the control group (P＜0.05) . Fewer adverse reactions were observed in the observation group than those in the control group (8.00% vs 26.00%, P＜0.05) . Conclusion Buqi Wenyang Dingkuang Decoction has a certain effect on mania patients with upfloating of asthenia yang type, and can significantly improve their cognitive function and sleep quality.

Quetiapine (QT) belongs to the second generation of antipsychotics. It is mostly used to treat depression, bipolar disorder, and schizophrenia. During biotransformation via myeloperoxidase (MPO) QT is oxidized to quinoneimine and a reactive radical, which may contribute to the development of oxidative stress during intoxication. The coexisting inflammation may also significantly contribute to the disturbances in the course of QT poisoning. In this study, twenty-one patients poisoned with quetiapine were examined. The study aimed to assess the correlation between blood QT concentration and selected oxidative stress as well as inflammation biomarkers, such as MPO and C-reactive protein (CRP) levels in the serum of poisoned patients. The obtained results were related to the values of the control group consisting of 21 healthy people, untreated and not poisoned with the drug. In patients with a toxic QT concentration in the blood (3.15 ± 2.11 μg/mL), the activity of MPO and CRP serum level were significantly higher in comparison to the control group. The mean level of CRP in the study group was 76.74 mg/L, while in the control group only 1.86 mg/L. The increase in MPO activity and CRP blood level in patients after QT overdose may confirm the hypothesis of oxidative disorders arising during its biotransformation and concomitant inflammation. Statistically significant relationships between selected biomarkers and blood QT concentration, the patient's clinical condition and the type of therapy were demonstrated.