Search

Electrochemical properties of quetiapine fumarate were examined on the anodic direction with multi‐walled carbon nanotube modified glassy carbon electrode using voltammetric methods. The ratio of multi‐walled carbon nanotube has been optimized using its various concentrations. The oxidation process was found to be irreversible, and adsorption controlled. The linear ranges were determined as 4×10−9–2×10−6 M for differential pulse stripping voltammetry and 2×10−9–2×10−6 M for square‐wave stripping voltammetry with detection limits of 8.07×10−10 and 2.71×10−10 M, respectively. The methods were validated and successfully applied for the analysis of quetiapine fumarate tablets. The groups responsible for the oxidation reaction of quetiapine fumarate were investigated with model substances. [ABSTRACT FROM AUTHOR]

A case study of a 68-year-old male with Parkinsonian type multiple system atrophy (MSA) who achieved remission of psychosis after treatment with modified electroconvulsive therapy (mECT) following unsuccessful antipsychotic treatments. It mentions that MSA is a progressive neurodegenerative disease that can be challenging to manage because it is frequently accompanied by other symptoms, including psychosis, postural instability, urinary incontinence, depression, and sleep disturbances.

Background and aim: There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia‐related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia‐related death with specific antipsychotic exposure. Method: Deaths analysed were those reported to a UK‐based drug‐related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case–control study with cases defined as pneumonia‐related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post‐mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders. Results: There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia‐related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15–1·55]; prescribed AOR 1·28 [95% CI 1·11–1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77–1·47]; prescribed AOR 0·91 [95% CI 0·71–1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22–1·82]; prescribed AOR 1·44 [95% CI 1·18–1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07–1·66]; prescribed AOR 1·28 [95% CI 1·01–1·64]). Conclusion: Olanzapine and quetiapine were found to increase the risk of pneumonia‐related death in this NPSAD sample to a clinically important extent. [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]

Background: Pimavanserin is currently the only antipsychotic approved for Parkinson's disease (PD) psychosis, yet its relative safety compared with treatment alternatives has not been thoroughly assessed. Objectives: This study aimed to compare hospitalization and mortality risk in Medicare beneficiaries with PD receiving new prescriptions of pimavanserin or quetiapine for PD psychosis. Methods: The study identified new users of pimavanserin and quetiapine from a 15% national sample of Medicare fee‐for‐service claims collected between May 1, 2016, and December 30, 2018. All‐cause hospitalization and mortality were assessed in time‐to‐event regression models. Standardized mortality ratio weighting balanced pimavanserin and quetiapine users on baseline characteristics. Follow‐up was censored at discontinuation, switch, disenrollment, or the end of the study period. Results: There were 844 new pimavanserin users and 2505 new quetiapine users. The adjusted hazard ratios (95% confidence intervals [CIs]) for hospitalization at 30, 90, 180, and 365 days for pimavanserin versus quetiapine users were 0.59 (0.43–0.81), 0.56 (0.44–0.72), 0.63 (0.52–0.77), and 0.70 (0.60–0.83). The most common reasons for hospitalization were traumatic injury and sepsis. Hospitalizations for heart‐related issues were higher with pimavanserin (P < 0.05). The adjusted hazard ratios (95% CIs) for all‐cause mortality at 90, 180, and 365 days for pimavanserin versus quetiapine users were 0.73 (0.48–1.13), 0.80 (0.58–1.10), and 0.94 (0.74–1.19). Conclusions: Risk of hospitalization was lower in pimavanserin users compared with quetiapine, and no difference in mortality was observed between pimavanserin and quetiapine. An active comparator analyses with treatment alternatives provided the most clinically relevant information for patients and physicians. [ABSTRACT FROM AUTHOR]

Aims: Quetiapine is widely used to treat psychiatric disorders such as major depression, generalized anxiety disorder, dysthymic disorder, and insomnia other than schizophrenia and bipolar disorder. This study investigated the diagnostic distribution of quetiapine use in patients in a psychiatric hospital, the doses of quetiapine prescribed, and the plasma concentrations (Cps) of quetiapine and active metabolites. Methods: We enrolled 107 patients who had been prescribed quetiapine for at least 4 weeks. Diagnoses, demographics, and concomitant medications were recorded. Blood sampling was performed in the morning, approximately 12 h after the before‐bed dose of quetiapine. Results: Diagnoses comprised schizophrenia (n = 25), bipolar disorder (n = 51), major depression (n = 15), dysthymic disorder (n = 9), and others (n = 7). The daily dose (DD) of quetiapine ranged from 25 to 800 (175.9 ± 184.4) mg, with the mean Cp being 105.6 ± 215.3 ng/ml, with a mean Cps/DD ratio of 0.58 ± 0.55 ng/ml/mg. There was a moderate positive linear correlation between the dose and Cps of quetiapine (r = 0.60), and the interpatient variation in Cps/DD ratio was up to 26‐fold. Conclusion: Quetiapine is used in various doses to treat many psychiatric disorders other than psychosis, and it is usually prescribed as a secondary antipsychotic for symptoms such as insomnia or agitation. A wide interpatient variation of the Cps/DD ratio was noticed. Patients of East Asian descent may exhibit a 50% to 100% increase in the Cps/DD ratio for quetiapine compared with patients of Western descent. [ABSTRACT FROM AUTHOR]

Copyright of Geneesmiddelenbulletin is the property of Stichting Geneesmiddelenbulletin and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 levels 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. [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]

Trends in prescribing psychotropic drugs before and during pregnancy may have changed over the years, but actual information is lacking. We therefore compared and assessed the exposure and acceptance rates of classes of antipsychotic (+ lithium), anxiolytic, sedative/hypnotic, antidepressant, and psychostimulant before and during pregnancy in the past two decades. All singleton pregnancies with ≥1 prescription of psychotropic drug from six months before pregnancy until child's birthdate were identified in the pregnancy subset of the IADB.nl prescription database. The prescription patterns of psychotropics were distinguished as continuation rate (CR), initiation rate (IR), discontinuation rate (DR), total exposure rate (TER), and acceptance rate. Singleton pregnancies exposed to psychotropic drugs before and during pregnancy increased from 118.4 to 136.5 (per 1000 singleton pregnancies) between decades. Changing trends were observed in decade 2, including a high increase in the TER of antipsychotic class (3.3 to 6.8) and antidepressant class (23.0 to 40.6). A marked increase for individual drugs was seen for sertraline (TER: 0.6 to 6.6 and PAT: 35.3% to 82.5%), citalopram (TER: 2.3 to 10.0 and PAT: 51.1% to 74.6%), and quetiapine (TER: 0.4 to 3.1 and PAT: 57.1% to 66.0%). Although the total exposure rates of five classes of psychotropics in singleton pregnancies increased in decade 2, only antidepressant class had a higher acceptance rate during pregnancy. Certain SSRI antidepressants and atypical antipsychotics were more frequently prescribed in decade 2 than in decade 1, reflecting that treatment options were preferred for safer treatment choices. [ABSTRACT FROM AUTHOR]

Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium have yet to be verified. Hence, we conducted a randomized controlled pilot study to evaluate the efficacy of QTP monotherapy in patients with bipolar depression with mixed features defined by DSM-5 and compared the combination therapy of QTP plus valproate (QTP + V) versus QTP plus lithium (QTP + L) for those patients who responded insufficiently to QTP monotherapy. Data was analyzed according to the intent-to-treat population. Generalized linear mixed model was performed by using "nlme" package in R software. A total 56 patients were enrolled, among which, 35 patients responded to QTP alone, and 11 and 10 patients were randomly assigned to QTP + V and QTP + L group, respectively. Nearly 60% enrolled patients responded to QTP monotherapy at the first two weeks treatment. No statistically significant difference in efficacy between QTP + V and QTP + L was observed. In conclusion, QTP monotherapy appeared to be efficacious in patients with bipolar depression with mixed features, and for those who responded insufficiently to QTP, combining with either valproate or lithium appeared to have positive effects. [ABSTRACT FROM AUTHOR]

Background: Compliance with psychotropic dosage guidelines has been shown to improve mental health status, reduce severity of symptoms, and decrease adverse effects. However, guideline recommendations are not always implemented. While deviation from dosage recommendations may be clinically appropriate in some patients, variation can cause a lack of efficacy or patient harm. Aim: To evaluate the incidence of antidepressant and antipsychotic prescribing at doses outside the recommended range provided by local guidelines, TherapeuticGuidelines:Psychotropic. Method: This study is a retrospective clinical audit of 793 patients admitted to hospital between August 2018 and July 2019. Data were collected through extensive file and chart reviews of patients treated with any of the antidepressant and antipsychotic medications listed in the Psychotropic Dosage Guidelines. Descriptive statistical analyses were performed to determine frequencies and proportions. Results: The audit identified that 38.0% of patients received doses of antidepressants or antipsychotics outside the recommended range. Most antidepressants were prescribed within recommended doses (83.0%), with 10.5% above the recommended dose, and 6.2% below. Fewer antipsychotics were prescribed within the recommended range (56.8%), 2.8% were prescribed at doses above the recommended range, and 40.3% were prescribed at doses below the recommendation range. Quetiapine was frequently prescribed at doses lower than recommended. Conclusion: The audit revealed a substantial amount of prescribing outside the recommended dosage ranges. It also highlighted the necessity of reviewing policies to limit the use of off‐label, low‐dose quetiapine. Audit and feedback could target psychiatrists who seem to have the highest propensity to prescribe outside the recommended dosage ranges. [ABSTRACT FROM AUTHOR]

Purpose: Poor sleep during hospitalization is common and implicated in worse patient outcomes. Despite implementation of non-pharmacologic techniques, medications are still frequently required. The study objective is to assess the frequency of new medications administered for sleep in hospitalized patients and to review literature evaluating these drug therapies in the inpatient setting. Methods: This retrospective study included adult inpatients if they received a new medication for sleep during a 5-day period. Patients were excluded if the medication was continued from home or if sleep was not the documented indication. For the literature review, a MEDLINE search was conducted to identify studies pertaining to pharmacotherapy for sleep in hospitalized patients. Results: Of 1,968 patient-days reviewed, a medication for sleep was given for 166 patient-days (8.4%) in 78 patients. Melatonin was most commonly received (70.5%), followed by benzodiazepines (9.6%). A review of antihistamines, benzodiazepines, melatonin, quetiapine, trazodone, and Z-drugs (non-benzodiazepine hypnotics) was conducted and 23 studies were included. Conclusions: Despite widespread use of pharmacotherapy for sleep, there is a paucity of data evaluating use in the inpatient setting. Although there is significant heterogeneity among studies, melatonin has the strongest evidence for use and is an attractive option given its lack of adverse reactions and drug interactions. Benzodiazepines and Z-drugs were also frequently utilized; however, their reduced clearance in the elderly and potential for compounded sedative effects should be weighed heavily against potential sleep benefits. Antipsychotic agents cannot be recommended for routine use due to limited data and the potential for significant adverse effects. [ABSTRACT FROM AUTHOR]

There is paucity of data on sexual dysfunction associated with atypical antipsychotics in Indian population. We estimated the prevalence of sexual dysfunction and assessed dose dependency, if any, in patients on monotherapy of atypical antipsychotics. This cross‐sectional study analyzed the data from patients with F20 to F29 (International Classification of Diseases 10th Revision, ICD‐10) receiving monotherapy of risperidone (group 1), olanzapine (group 2), or quetiapine (group 3) for at least 4 weeks. The sexual function of participants was assessed using Arizona sexual experiences (ASEX) scale. Chlorpromazine (CPZ) equivalent dose and doses in terms of dose years were calculated. Kruskal–Wallis test, Mann–Whitney U‐test, and Pearson correlation were used for analysis. Of the 154 subjects, 65.58% were males, with 44%, 48%, and 8% receiving risperidone, olanzapine, and quetiapine, respectively. The mean duration of treatment was 20.9 weeks. Lower ASEX scores were reported with quetiapine. The differences in mean ASEX scores between groups 1 and 2 were statistically significant for sex drive (P =.016), sexual arousal (P =.025), and overall score (P =.037). Sexual dysfunction was more frequent with risperidone (48.5%) than with olanzapine (28.4%) and quetiapine (0%). In group 1, the duration of therapy positively correlated with the mean scores of sexual desire (P =.003) and arousal (P =.033), but this was not the case for group 2 (receiving olanzapine). The mean CPZ equivalent doses were comparable between the groups (P =.064); those receiving <200 mg CPZ dose equivalents showed greater sexual impairment. We conclude that the occurrence of atypical antipsychotic‐induced sexual dysfunction is not dose dependent. Olanzapine has a better safety profile in terms of sexual dysfunction, whereas the data reflecting the experience with quetiapine are insufficient. [ABSTRACT FROM AUTHOR]

Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series. [ABSTRACT FROM AUTHOR]

Objective: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4–0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. Results: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP (N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) (p = 0.59). Users of Li+AC (N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC (N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general (p = 0.05) and manic symptoms (p = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome. Conclusion: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic. [ABSTRACT FROM AUTHOR]

Objective: Quetiapine use at standard doses has been associated with hyperglycemia and dyslipidemia. However, whether even frequently prescribed low‐dose quetiapine results in significant metabolic disturbances remains unclear. Thus, this study aimed to investigate the association between off‐label, low‐dose quetiapine and changes in glycosylated hemoglobin (HbA1c) levels/lipid parameters. Methods: We identified new users of low‐dose quetiapine (≤50 mg tablets) in Denmark 2008–2018 with measurements of HbA1c, total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), or fasting triglycerides (fTG) within 365 days before and after quetiapine initiation. Mixed‐effects linear regression models were used to estimate coefficients (β) with 95% confidence intervals (95%CIs) for change in cardiometabolic parameters after quetiapine initiation. Inverse probability weighting was used to mitigate selection bias. Higher doses of quetiapine (>50 mg) were included in sensitivity analyses. Results: Among 106,711 eligible new low‐dose quetiapine users (median age = 45 years, females = 55%), low‐dose quetiapine initiation was associated with increased fTG (β = 1.049[95%CI:1.027–1.072]) and decreased HDL‐C (β = 0.982[0.978–0.986]). Although HbA1c did not change significantly and TC and LDL‐C even decreased considering all subjects, all three metabolic parameters increased significantly among individuals with normal pre‐quetiapine initiation levels. The adverse metabolic effect of quetiapine on HbA1c, TC, LDL‐C, and HDL‐C was dose‐dependent, which was not the case for fTG. Conclusions: Low‐dose quetiapine was associated with a significant increase in fTG and decreases in HDL‐C in all subjects, as well as with significant increases in HbA1c, TC, and LDL‐C among those with normal baseline values. The risk of metabolic worsening with quetiapine was dose‐dependent, except for fTG. [ABSTRACT FROM AUTHOR]

Copyright of ESPOCH Congresses: The Ecuadorian Journal of S.T.E.A.M. is the property of Knowledge E DMCC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Hypothesis Throughout the life stages of women with schizophrenia-spectrum disorders (SSD), lower estrogen levels are associated with more severe disease course. At perimenopause in the mid-forties, estrogen levels decline to remain persistently low after menopause. This period is hypothesized to increase relapse risk and reduce antipsychotic effectiveness in preventing relapse. Study Design The cohort of persons with schizophrenia/schizoaffective disorder was identified from Finnish nationwide registers (N = 61 889) and stratified by sex and age <45 vs. ≥45 years. Hospitalizations for psychosis were defined per 5-year age group during the follow-up 1996–2017. Risk of psychosis hospitalization (Adjusted Hazard Ratio, aHR) was assessed using within-individual design, by comparing antipsychotic monotherapy use to nonuse periods in the same individuals for seven dose categories in defined daily doses (DDDs/day). Results Starting at age 45–50, women were consistently more often hospitalized for psychosis than their male peers. Women ≥45 had significantly higher aHRs than women <45 at antipsychotic monotherapy >0.6 DDDs/day, and than men at >1.1 DDDs/day. This female-specific age-dependent decrease in effectiveness was present for clozapine doses >0.6 DDDs/day, olanzapine doses >1.4 DDDs/day, and for specific doses of quetiapine (0.9–1.1 DDDs/day) and risperidone (0.6–0.9 DDDs/day). Conclusions While younger women have a lower risk of relapse and generally need a lower antipsychotic dose to prevent rehospitalization than men, antipsychotic effectiveness declines in women after the age of 45. Starting in mid-forties, older women with SSD should be regarded as a vulnerable group that deserve special attention. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Complex schizophrenia symptoms were recently conceptualized as interactive symptoms within a network system. However, it remains unknown how a schizophrenia network changed during acute antipsychotic treatment. The present study aimed to evaluate the interactive change of schizophrenia symptoms under seven antipsychotics from individual time series. Study Design Data on 3030 schizophrenia patients were taken from a multicenter randomized clinical trial and used to estimate the partial correlation cross-sectional networks and longitudinal random slope networks based on multivariate multilevel model. Thirty symptoms assessed by The Positive and Negative Syndrome Scale clustered the networks. Study Results Five stable communities were detected in cross-sectional networks and random slope networks that describe symptoms change over time. Delusions, emotional withdrawal, and lack of spontaneity and flow of conversation featured as central symptoms, and conceptual disorganization, hostility, uncooperativeness, and difficulty in abstract thinking featured as bridge symptoms, all showing high centrality in the random slope network. Acute antipsychotic treatment changed the network structure (M-test = 0.116, P <.001) compared to baseline, and responsive subjects showed lower global strength after treatment (11.68 vs 14.18, S-test = 2.503, P <.001) compared to resistant subjects. Central symptoms and bridge symptoms kept higher centrality across random slope networks of different antipsychotics. Quetiapine treatment network showed improvement in excitement symptoms, the one featured as both central and bridge symptom. Conclusion Our findings revealed the central symptoms, bridge symptoms, cochanging features, and individualized features under different antipsychotics of schizophrenia. This brings implications for future targeted drug development and search for pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Electronic cigarette (e-cigarette) or vaping associated lung injury (EVALI) cases have increased with the popularity of e-cigarettes in the mostly young, healthy population. Some common symptoms associated with EVALI include shortness of breath and chest pain, and the most common diagnostic imaging findings are organizing pneumonia and diffuse alveolar damage seen on computed tomography (CT). Pneumomediastinum is a known sequela of EVALI.1 In the setting of pneumomediastinum in EVALI, EVALI is a diagnosis of exclusion, so other sources of pneumomediastinum need to be evaluated. EVALI has diverse presentations, and this case is a unique representation of a disease process that is becoming more commonplace with the increase in popularity of vaping. It is important to be aware of the clinical symptoms of EVALI, which can be nonspecific and can include gastrointestinal symptoms along with respiratory symptoms. It is equally important to recognize the diverse image findings of EVALI, which can include subcutaneous emphysema and pneumomediastinum. In this case, pneumomediastinum is seen in EVALI, and the patient was successfully treated with empiric antibiotic coverage, steroids, and conservative measures-- making sure to limit any coughing or increases in intrathoracic pressure that can cause worsening of pneumomediastinum. Topics: EVALI, vaping, pneumomediastinum, E-cigarette, ground-glass opacity. [ABSTRACT FROM AUTHOR]

Background: Delirium is a severe complication in critical care patients. Accurate prediction could facilitate determination of which patients are at risk. In the past decade, several delirium prediction models have been developed. Objectives: To compare the prognostic accuracy of the PRE-DELIRIC, E-PRE-DELIRIC, and Lanzhou models, and to investigate the difference in prognostic accuracy of the PRE-DELIRIC model between patients receiving and patients not receiving mechanical ventilation. Methods: This retrospective study involved adult patients admitted to the intensive care unit during a 2-year period. Delirium was assessed by using the Confusion Assessment Method for the Intensive Care Unit or any administered dose of haloperidol or quetiapine. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC); values were compared using the DeLong test. Results: The study enrolled 1353 patients. The AUC values were calculated as 0.716 (95% CI, 0.688–0.745), 0.681 (95% CI, 0.650–0.712), and 0.660 (95% CI, 0.629–0.691) for the PRE-DELIRIC, E-PRE-DELIRIC, and Lanzhou models, respectively. The difference in model discrimination was statistically significant for comparison of the PRE-DELIRIC with the E-PRE-DELIRIC (AUC difference, 0.035; P =.02) and Lanzhou models (AUC difference, 0.056; P <.001). In the PRE-DELIRIC model, the AUC was 0.711 (95% CI, 0.680–0.743) for patients receiving mechanical ventilation and 0.664 (95% CI, 0.586–0.742) for those not receiving it (difference, 0.047; P =.27). Conclusion: Statistically significant differences in prognostic accuracy were found between delirium prediction models. The PRE-DELIRIC model was the best-performing model and can be used in patients receiving or not receiving mechanical ventilation. [ABSTRACT FROM AUTHOR]

Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits. To examine annual HCRU among newly initiated PIM or QUE monotherapy among patients with PDP. Retrospective analysis of 100% Medicare (Parts A, B, and D) claims of patients with PDP during 1 January 2013 to 31 December 2019 was conducted. Treatment-naive patients with first prescription for PIM or QUE from 1 January 2014 to 31 December 2018 were selected if they had ≥12-months continuous monotherapy and had no prior AAP use for ≥12-month pre-index. Post-index 12-month HCRU was compared between 1:1 propensity score matched (PSM) PIM or QUE cohorts. HCRU outcomes included: rates of all-cause and psychiatric-related inpatient hospitalizations by stay-type [i.e., long-term stays (LT-stays), short-term stays (ST-stays), skilled nursing facility stays (SNF-stays)], outpatient hospitalizations, emergency room (ER) visits, and office visits. Relative risk and 95% confidence intervals are reported [RR (95% CI)]. A total of 842 and 7,116 were treated with PIM and QUE, respectively. Mean age and gender distribution were similar among both groups. After PSM, those on PIM (n=842) had significantly lower RR for all-cause: inpatient hospitalizations [RR=0.78 (0.70–0.87)], ST-stays [RR=0.75 (0.66–0.84)], SNF-stays [RR=0.64 (0.54–0.76)], and ER visits [RR=0.91 (0.84–0.97)] vs. QUE (n=842). PIM patients had slightly higher RR for all-cause office visits [RR=1.03 (1.01–1.05)] vs. QUE. Psychiatric-related inpatient hospitalizations were also lower for PIM vs. QUE: [RR=0.63 (0.48–0.82)] ST-stays [RR=0.61 (0.43–0.86)], SNF-stay [RR=0.69 (0.47–1.02)], and ER visits [RR=0.53 (0.37–0.76)]. In this analysis of PDP patients, PIM monotherapy resulted in nearly 22% and 37% lower all-cause hospitalizations and psychiatric-related inpatient hospitalizations compared to QUE. [ABSTRACT FROM AUTHOR]

Oculogyric crisis (OGC) is an acute paroxysmal sustained dystonia that occurs as an adverse drug event, commonly following first-generation antipsychotics and rarely with second-generation antipsychotics. We report a case of quetiapine (QTP)-induced disabling and stigmatizing tardive OGC developing after a month of its initiation, at a substantive low-dose (100 mg/day) in an ectomorphic young adult female during concomitant QTP, fluoxetine, and lithium therapy. It responded well to anticholinergic medications alone, without the need for dose-reduction or discontinuation of medications. We review literature on OGC due to QTP, fluoxetine and lithium; and discuss putative mechanisms leading to OGC in our case.

Lack of evidence to guide medication treatments for mild traumatic brain injury (mTBI) in veterans too often results in polypharmacy practices attempting to provide symptomatic relief from multiple postconcussive syndrome symptoms. Therefore, the field needs to find an effective medication that reduces the burden of postconcussive symptoms without complicating the treatment burden of veterans. This clinical trial seeks to determine whether switching veterans to quetiapine monotherapy (intervention) is superior to continuing to receive treatment as usual (TAU, control) polypharmacy for veterans with symptoms of postconcussive syndrome and posttraumatic stress disorder who are receiving rehabilitation treatment for mTBI. This study will test the conceptual mediation model hypothesis that quetiapine monotherapy may enhance recovery from mTBI by (1) increasing engagement in rehabilitation services, and/or (2) reducing the adverse effects of TAU polypharmacy. This study will enroll 146 patients from two Veterans Administration Medical Centers into a 12- week phase III, randomized, pragmatic clinical trial comparing outcomes from treatment with quetiapine monotherapy and TAU. Quetiapine will be cross tapered up to a maximum dose of 200 mg (as tolerated) as other medications are discontinued. The primary outcome measures are postconcussive syndrome symptoms (Neurobehavioral Symptom Inventory), functional disability (World Health Organization Disability Assessment), and quality of life (World Health Organization Quality of Life Assessment). Overall, this study aims to determine whether quetiapine monotherapy is superior to TAU polypharmacy and improves the quality of life for veterans with comorbid postconcussive syndrome and posttraumatic stress disorder symptoms who are receiving rehabilitation treatment for mTBI. [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 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.

Background: Fibromyalgia (FM) and major depression disorder (MDD) frequently co-occur. Both disorders may share common serotonergic alterations, although there is less evidence of such alterations in FM. It is also unclear as to whether these alterations are persistent over time or transient. The objectives of this study were to (i) examine the changes in mRNA expression of serotonin transporter (SERT) on the surface of peripheral blood mononuclear cells (PBMCs) in FM, MDD, and the FM + MDD subjects compared to healthy controls, and to (ii) evaluate the effect of drug treatment on SERT expression. Methods: PBMCs were isolated from FM, MDD, FM + MDD, and control subjects. SERT expression was analyzed at the mRNA level via quantitative real-time polymerase chain reaction. Statistical analyses were performed using analyses of variance and linear mixed-effects models. Results: SERT mRNA expression was significantly reduced in MDD subjects compared to controls (p < 0.001), but not in FM nor in FM + MDD subjects. Although the drug treatments improved symptoms in FM, MDD, and FM + MDD subjects, they had no significant effect on SERT mRNA expression. Conclusions: These results corroborate the role of the SERT in the pathophysiology of MDD, but not in FM, and show that the decreased mRNA expression of SERT is a persistent, rather than transient, phenomenon.

The article focuses on a case study regarding mania triggered by intermittent theta burst stimulation (iTBS) in a patient with bipolar affective disorder. The case study discusses the unique features of the manic switch, the use of mood stabilizers, and the possible role of TMS (transcranial magnetic stimulation) in mood switch. It also highlights the need for caution when administering stimulatory protocols like iTBS in patients.

In the present project, we have applied a molecular imprinted polymer (MIP) for the solid phase extraction (SPE) of quetiapine residue from human blood plasma. This study aimed to develop a method for determination of the bioavailability of quetiapine as a widely used antipsychotic in the blood serum. The extraction of quetiapine from the plasma was optimized and the loading amount (LA) for its adsorption was determined. Subsequently, a HPLC‐UV/VIS method was validated and applied to analyze the concentration of the mentioned drug which was extracted from the blood serum. The results showed that the limit of detection (LOD), and the limit of quantification (LOQ) for the validated MIP‐SPE approach were about 0.0172 ng ml−1, and 0.0481 ng ml−1, respectively. Finally, each of the MIP, and the non‐imprinted polymer (NIP), and their complex with the guest drug were designed and optimized by the density functional theory (DFT) approach. Based on our theoretical calculations, the structural properties, as well as the reactivity parameters (the molecular descriptors) were extracted, and debated. The results of the theoretical calculations showed a good agreement with the experimental results. Those results confirmed the favorability of adsorption of the drug by MIP compared to NIP. [ABSTRACT FROM AUTHOR]

Background: Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes. Methods: We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications. Results: The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69). Conclusions: There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes. [ABSTRACT FROM AUTHOR]

Aim: No consensus has been reached on the association between the risk of falls and antipsychotic and antidepressant drug use. In this study, we evaluated the risk of falls with trazodone, risperidone, and quetiapine, which are recommended for use at Kanazawa Medical University Hospital. Methods: We reviewed all patients who were admitted to Kanazawa Medical University Hospital between January 1st and December 31st, 2018. We excluded those aged <20 years and those admitted to pediatric, intensive care, and psychiatric wards. Finally, 9273 patients were included. We reviewed the incidence in these patients of accidental falls reported to the medical safety department. We noted whether these patients received trazodone, quetiapine, or risperidone. We also observed whether they were taking a benzodiazepine receptor agonist, which is a known risk factor. We further examined each patient's age, sex, the department they were visiting, and their diseases. Patients were considered to have taken medication if it was administered within 24 hours before an accidental fall. Multiple logistic regression analysis was used to evaluate the risk of accidental fall. Results: Multivariate analysis showed that the adjusted odds ratios (OR) for each medication (with 95% confidence intervals) were: trazodone (OR, 0.47 [0.27–0.80]), quetiapine (OR, 1.06 [0.46–2.46]), and risperidone (OR, 0.82 [0.41–1.63]). Conclusion: The association of risperidone and quetiapine with accidental falls was unclear. Interestingly, however, trazodone may help reduce the risk, which makes it a potential pharmacologic treatment option for insomnia in patients at high risk for accidental falls. [ABSTRACT FROM AUTHOR]

Aim: Pharmacological treatments recommended for bipolar depression are inconsistent across guidelines. We compared the efficacy and safety of antipsychotics and mood stabilizers for bipolar depression. Methods: A systemic review and meta‐analysis of randomized controlled trials comparing antipsychotics and mood stabilizers for bipolar depression was conducted based on a literature search of major electronic databases. Results: Three studies comparing quetiapine with lithium were identified and analyzed; no other antipsychotic‐mood stabilizer combinations were found. The meta‐analysis revealed no significant differences between quetiapine and lithium for the following outcomes: (1) remission from depressive episodes (risk ratio [RR]: 1.80, 95% CI: 0.51‐6.40, P = 0.36), (2) changes in depressive symptom (standardized mean difference: −0.22, 95% CI: −0.52‐0.08, P = 0.15), (3) changes in social function (standardized mean difference: −0.00, 95% CI: −0.19‐0.18, P = 0.98), (4) suicide‐related events (odds ratio [OR]: 2.35, 95% CI: 0.40‐13.65, P = 0.34), (5) severe adverse events (OR: 1.63, 95% CI: 0.51‐5.20, P = 0.41), (6) dropouts due to adverse events (RR: 1.19, 95% CI: 0.76‐1.87, P = 0.45, 7) dropout for any reasons (RR: 0.95, 95% CI: 0.74‐1.22, P = 0.70). Conclusion: Although this study found no differences in the efficacy and safety of quetiapine and lithium for bipolar depression, a comprehensive comparison of antipsychotics and mood stabilizers was not performed. Further studies are needed to clarify which of these, not just quetiapine and lithium, is more useful for bipolar depression. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Serotonin toxicity, often referred to as 'serotonin syndrome,' is a drug-induced condition due to excess serotonin released from brain synapses, resulting in symptoms that may be autonomic, neuromuscular, and/or cognitive in nature. Most cases involve more than 1 of the following drug regimens: monoamine oxidase inhibitors (MAOIs), serotonin releasers, selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). This report is of a 70-year-old woman who presented with confusion and muscle spasms due to serotonin toxicity associated with paroxetine and quetiapine treatment. Case Report: An elderly woman with dementia presented to the Emergency Department with fever, altered mental status, labile blood pressures, and inducible clonus. No known medication dosage increases had been made, nor had any new serotonergic agents been added to the patient's drug regimen. She underwent a thorough workup in the Emergency Department and later during her hospitalization. A presumptive diagnosis of serotonin toxicity was made early on during her stay, with the etiology attributed to use of paroxetine and quetiapine. Clinical improvement was observed after benzodiazepine administration, discontinuation of offending agents, and a brief cyproheptadine course. The patient survived her hospital stay and was ultimately discharged to hospice care with a return to her baseline level of functioning. Conclusions: Diagnosing serotonin toxicity requires a high degree of clinical suspicion and can occur in the absence of increased dosage of existing, or initiation of new, serotonergic agents. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a pivotal role in the etiopathology of Major Depressive Disorder (MDD), at least in a subset of patients. It is crucial to first establish which specific inflammatory biomarkers are of clinical utility. Anti-cardiolipin antibody (aCL IgM) is an inflammatory marker that has the potential to be such a candidate but there are insufficient studies to confirm this potential. Objective: To investigate the baseline titer level and the longitudinal progression of plasma titers of aCL IgM in MDD subjects receiving antidepressant therapy in comparison to healthy control (HC) subjects; to determine if changes in aCL IgM plasma titers correlate to changes in depressive symptoms; and, to ascertain if baseline aCL IgM plasma titers could predict treatment response. Methods: Forty-eight medically healthy outpatients diagnosed with MDD were enrolled in one of two groups in two sequentially conducted clinical trials. In Group-E, patients received a 12-week regimen of escitalopram (n = 20). Those in Group-Q received a 12-week regimen of quetiapine (n = 28). The main outcome measure was plasma aCL IgM titers, the Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). There were 16 HC subjects. Results: When Group-Q and Group-E participants were grouped together (n = 48), MDD subjects had an elevated baseline aCL IgM (19.9 μg/mL) compared to HC subjects (8.32 μg/mL) (p = 0.006). aCL IgM correlated significantly with HAM-D17 scores at baseline in MDD subjects (p = 0.0185, r = 0.296). Examining the individual groups, Group-Q MDD patients had a significantly elevated baseline aCL IgM (p = 0.008) while Group-E's MDD patients did not. On the other hand, only Group-E MDD patients showed a significant correlation at baseline between aCL IgM and HAM-A score (p = 0.0392, r = 0.4327); they also showed a significant inverse correlation between week 12 HAMD-17 Item #10 (Anxiety, Psychic) and week 12 aCL IgM titer (p = 0.0268, r = −0.5516). Conclusions: MDD patients had significantly higher plasma titers of aCL IgM when compared to HC subjects. Moreover, at baseline, the higher the aCL IgM titer, the higher the depression severity, as measured by HAMD-17 score. However, this study did not demonstrate that aCL IgM titers changed significantly throughout a 12-week course of antidepressant treatment and revealed no correlation between changes in depressive symptoms and changes in aCL IgM titers. Baseline aCL IgM could not predict treatment response. We conclude that, despite lacking predictive ability as regards treatment response, plasma titers of aCL IgM have a diagnostic potential in MDD that necessitates further exploration. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is frequently prescribed to people with personality disorder diagnoses, but this is not supported by evidence or treatment guidelines. Aims: To examine associations between periods of quetiapine prescribing and self-harm events in people with personality disorder. Method: Self-controlled case series using linked primary care and hospital records covering the period 2007–2017. We calculated incidence rates and incidence rate ratios (IRRs) for self-harm events during periods when people were prescribed (exposed to) quetiapine, as well as periods when they were unexposed or pre-exposed to quetiapine. Results: We analysed data from 1,082 individuals with established personality disorder diagnoses, all of whom had at least one period of quetiapine prescribing and at least one self-harm episode. Their baseline rate of self-harm (greater than 12 months before quetiapine treatment) was 0.52 episodes per year. Self-harm rates were elevated compared to the baseline rate in the month after quetiapine treatment was commenced (IRR 1.85; 95% confidence interval (CI) 1.46–2.34) and remained raised throughout the year after quetiapine treatment was started. However, self-harm rates were highest in the month prior to quetiapine initiation (IRR 3.59; 95% CI 2.83–4.55) and were elevated from 4 months before quetiapine initiation, compared to baseline. Conclusion: Self-harm rates were elevated throughout the first year of quetiapine prescribing, compared to the baseline rate. However, rates of self-harm reduced in the month after patients commenced quetiapine, compared to the month before quetiapine was initiated. Self-harm rates gradually dropped over a year of quetiapine treatment. Quetiapine may acutely reduce self-harm. Longer-term use and any potential benefits need to be balanced with the risk of adverse events. [ABSTRACT FROM AUTHOR]

Recent studies implicate a key role of dopamine signaling in lifespan regulation. Our previous study found that quetiapine, an atypical antipsychotic drug that has antagonistic activity on dopamine D2-like receptors (D2Rs), shortened the lifespan of Caenorhabditis elegans (C. elegans). However, the detailed mechanism of this effect was not clear. In the present study, we evaluate the effect of quetiapine on aging and explore its underlying molecular mechanism. The results show that quetiapine shortened healthspan in C. elegans. The lifespan-shortening effect is dependent on DOP-2, a D2R expressed in worms. Quetiapine shortens lifespan through the C. elegans insulin and IGF-1 receptor DAF-2, but not the downstream Akt pathway. Quetiapine-induced lifespan reduction is dependent on RSKS-1, a key protein kinase that functions in mTOR signaling. In addition, the quetiapine effect is also related to mitochondrial function. These findings further support the key role of dopamine signaling in lifespan regulation and promote our insight into the mechanism of action of antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies proposed the existence of a correlation between patients' inflammatory status and therapy response in bipolar disorder (BD). Here we investigated the correlation between levels of inflammatory markers and quetiapine (QUE) effects in BD patients. Methods: In 15 hospitalised BD patients, we investigated changes in inflammatory markers such as C‐Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and cytokines after a 6‐week treatment with QUE monotherapy. Results: We found QUE treatment to significantly reduce CRP and IL‐6 plasma levels. Moreover, we found higher CRP and IL‐6 plasma levels at baseline correlated with better improvement of patients' clinical symptoms. Conclusion: The reported results, although preliminary, could be useful in clinical practice, providing not only markers for QUE response, but also allowing for identification of new targets and new therapies for the treatment of this condition. [ABSTRACT FROM AUTHOR]

Background and aims. Prompt recognition and optimal management of hyponatremia helps the physician devise a better treatment plan to prevent future complications in patients. Hence this study aims to identify the risk factors associated with hyponatremia in psychiatric patients. Methods. A case-control study was conducted among psychiatric inpatients in a tertiary care teaching hospital. Patients admitted from January 2013 to December 2017 were identified using ICD-10 code F01-F99. Patients with serum sodium levels < 135 mmol/L were considered to have hyponatremia and between 135-145 mmol/L as controls. Factors associated with hyponatremia were identified by multiple logistic regression, and the odds ratio (OR) was calculated. Results. Based on the inclusion and exclusion criteria, 264 cases of hyponatremia and 253 matching controls were included in the study. The mean age of patients with hyponatremia was 56.4 ± 16.8 years compared to 39.6 ± 13.9 years in controls, and 65.7% of them were males. Seizure disorder (OR = 3.14, p = 0.047), bipolar disorder (OR = 6.03, p = 0.001), depression (OR = 4.78, p = 0.0005), use of quetiapine (OR = 2.11, p = 0.007) and insulin (OR = 3.53, p = 0.038) were independent risk factors associated with development of hyponatremia. Conclusions. The chances of developing hyponatremia are increased in psychiatric patients with a seizure disorder, bipolar disorder, depression and using quetiapine or insulin. And they should be monitored carefully. [ABSTRACT FROM AUTHOR]

A 52-year-old male patient, with metabolic syndrome, Human Immunodeficiency Virus (HIV), insomnia, generalized anxiety disorder, schizophrenia and analgesic medication, who has been suffering from numerous nocturnal episodes of insomnia and restlessness. He had to be rescued by the emergency service when presenting a state of great confusion, agitation and a deep and marked tachycardia. The medication review allows us to associate these adverse events with an excess dose of quetiapine caused by the interaction with darunavir. The intervention consists of informing the doctor of the suspected influence of the interaction of darunavir with quetiapine and proposing the substitution of the antipsychotic for another that uses a different metabolic pathway. Darunavir is expected to increase the plasma concentrations of these antipsychotics, such as quetiapine (CYP3A inhibition). Co-administration of darunavir and quetiapine may be potentially serious as quetiapine-associated toxicity may be increased. The psychiatrist substitutes quetiapine for clotiapine. As of this change in medication, the patient no longer experiences any of the problems that afflicted him, in addition to the fact that he has regained sleep. [ABSTRACT FROM AUTHOR]

Copyright of Spektrum der Augenheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although quetiapine metabolism occurs extensively in the liver and careful dosing is recommended in patients with liver disease, there has been a paucity of pharmacometric studies to adjust the clinical dose of quetiapine according to liver-disease severity. This study aimed to establish a whole-body, physiologically-based pharmacokinetic (WB-PBPK) model to explain interindividual variability in quetiapine PK and quantitatively predict PK in patients with liver disease. The developed WB-PBPK model well described the PK characteristics of different quetiapine regimens in healthy populations. The PK predictions could also be applied to patients with schizophrenia (without significant differences from healthy subjects). For the same total dose of quetiapine, both immediate-release (IR) and extended-release (ER) tablets showed significantly increased exposure and decreased clearance in patients with liver disease compared to healthy subjects. The model showed that steady-state plasma quetiapine concentrations exceeded the usual therapeutic range after multiple doses of IR tablets 250 mg three times daily or ER tablets 800 mg once daily in patients with liver disease. Therefore, the doses of quetiapine IR or ER tablets could be reduced by 0.10-0.50 times depending on liver-disease severity, so that mean steady-state plasma concentrations could be positioned near the therapeutic range. WB-PBPK modeling for quetiapine enabled quantitative prediction of PK according to IR or ER formulation and liver-disease severity. The results of this study provide useful data for improving the therapeutic use of quetiapine by enabling dose selection based on formulation and liver-disease severity., Competing Interests: Declarations. Conflict of Interest: The authors have no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Objective: Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug-drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK)., Methods: Ninety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs., Results: It was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40-50 and 50-120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40-120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range., Conclusion: The present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang, Yin, Jin, He, Liu, Zhang and Wang.)

Long-term sample stability of five atypical antipsychoticdrugs risperidone, paliperidone, clozapine, quetiapine and olanzapine and the antidepressant drug mirtazapine in serum was studied by use of a newly developed and validated analytical method based on solid-phase extraction and liquid chromatography-tandem mass spectrometry. Ascorbic acid was used as an antioxidative agent to stabilize olanzapine during storage and sample preparation. We assessed analyte stability on long-term storage in serum samples at 25°C, 5°C, -20°C and -80°C, and during five freeze-thaw cycles. Analytes were stable for 23 days at room temperature except for olanzapine and mirtazapine (17 days). All analytes were stable for at least 30 days at 5°C. All analytes were stable for 270 days at -20°C, except for paliperidone and mirtazapine with 60 days and 180 days, respectively. All analytes were stable for 270 days at -80°C. Furthermore, all analytes were stable for five freeze-thaw cycles. We recommend storage at -80°C when samples drawn for analysis of antipsychotic drugs are stored for more than 60 days, whereas a temperature of -20°C is sufficient for storage less than 60 days., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Aims: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 (CYP) enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine., Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analysed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating comedications) or with concomitantly applied metamizole, were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations., Results: Patients comedicated with metamizole showed >50% lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q 1  = 15.5; Q 3  = 90.5 vs. 92.0 ng/mL, Q 1  = 52.3; Q 3  = 203.8, P = .003). The dose-adjusted plasma concentrations were 69% lower in the comedication group (P = .001). Subgroup analyses did not suggest a dose dependency of the metamizole effect or an influence of quetiapine formulation (immediate vs. extended release). Finally, the comedication group exhibited a significantly higher proportion of patients whose quetiapine concentrations were below the therapeutic reference range (78.8% in the metamizole group vs. 54.4% in the control group, P = .037) indicating therapeutically insufficient drug concentrations., Conclusion: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, probably via an induction of CYP3A4. Clinicians must consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

A sustainable HPTLC-densitometric method was developed for quantitative determination of Quetiapine (QUET), Levodopa (LD) and Carbidopa (CD) in presence of Dopamine (DOP) as an internal standard. This applicable technique was achieved by spiking human plasma and extraction was performed using the protein precipitation approach. The mobile phase used was acetone, dichloromethane, n-butanol, glacial acetic acid and water (3: 2.5: 2: 2: 1.75, by volume). Method validation was done according to US-FDA guidelines and was able to quantify Quetiapine, Levodopa and Carbidopa in the ranges of 100-4000, 200-8000 and 30-1300 ng/mL, respectively. Bioanalytical method validation parameters were assessed for the studied drugs. Finally, the analytical suggested methodology was evaluated using various green and white analytical chemistry metrics and other tools, such as the green solvent selection tool, analytical eco-scale, green analytical procedure index, analytical greenness metric approach and the red-green-blue algorithm tool. The results revealed that the applied analytical method had a minor impact on the environment and is a relatively greener option than other previously reported chromatographic methods., (© 2024. The Author(s).)

Over the past decade, quetiapine has become one of the most commonly used psychotropic drugs in acute intoxication events worldwide. A structured literature review and analysis were conducted to assess the relationship between the kinetic and dynamic profiles in acute quetiapine intoxication. The correlation between dose and peak serum concentration (c max ) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and c max as predictors of the most common clinical events, signs and symptoms. One hundred and thirty-four cases of acute quetiapine ingestion were included in the analysis, with a median ingested dose of 10 g and a median c max of 4 mg/L. The typical half-life was estimated to be 16.5 h, significantly longer than at therapeutic doses. For the immediate-release formulation, a biphasic disposition could not be excluded. Dose and c max demonstrated a weak but significant correlation (r = 0.256; N = 63; p = 0.043). Central nervous system depression and tachycardia were the most common clinical signs. Higher doses and concentrations increased the risk of severe intoxication and were good predictors of intubation, tachycardia, hypotension, QT c prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and c max that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or c max > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.