UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: The quetiapine vs. atypical antipsychotic without QT prolongation warning 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 risks 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.
UNASSIGNED: 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.

BACKGROUND: Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky\'s sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens-Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy.
METHODS: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky\'s sign was positive. A diagnosis of Steven-Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission.
CONCLUSIONS: Stevens-Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

BACKGROUND: Depressive and anxiety symptoms commonly manifested throughout the progression of schizophrenia. However, the prevalence of these symptoms, alongside their co-occurrence, remains uncertain, and clinical correlates remain elusive.
OBJECTIVE: This study seeks to investigate the prevalence of such symptoms and their demographic and clinical associations among patients diagnosed with schizophrenia.
METHODS: The study included 19,623 patients diagnosed with schizophrenia based on the ICD-10 criteria. Participants were recruited from community-dwelling patients registered in the local health system in Hangzhou of China between August 1 and October 30, 2022.
RESULTS: The prevalence rates of depressive and anxiety symptoms, as well as their co-occurrence, were determined to be 19 % (95%CI = 18.5-19.6 %), 37.4 % (95%CI = 36.8-38.0 %), and 17.7 % (95%CI = 17.2-18.2 %), respectively. Patients prescribed quetiapine, olanzapine, and risperidone exhibited significantly lower prevalence rates of these symptoms (P < 0.01). Spearman\'s correlation analysis revealed a significant correlation between depressive symptoms and anxiety symptoms (r = 0.60, P = 0.006). Additionally, age, social relationships, and sleep status were significantly associated with depressive and anxiety symptoms, and their co-occurrence, in both univariate and multivariate analyses.
CONCLUSIONS: Given the pervasive nature and detrimental consequences of these symptoms among individuals diagnosed with schizophrenia, comprehensive evaluation and implementation of efficacious interventions are highly recommended.

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.

This study aims to optimize and evaluate drug release kinetics of Modified-Release (MR) solid dosage form of Quetiapine Fumarate MR tablets by using the Artificial Neural Networks (ANNs). In training the neural network, the drug contents of Quetiapine Fumarate MR tablet such as Sodium Citrate, Eudragit® L100 55, Eudragit® L30 D55, Lactose Monohydrate, Dicalcium Phosphate (DCP), and Glyceryl Behenate were used as variable input data and Drug Substance Quetiapine Fumarate, Triethyl Citrate, and Magnesium Stearate were used as constant input data for the formulation of the tablet. The in-vitro dissolution profiles of Quetiapine Fumarate MR tablets at ten different time points were used as a target data. Several layers together build the neural network by connecting the input data with the output data via weights, these weights show importance of input nodes. The training process optimises the weights of the drug product excipients to achieve the desired drug release through the simulation process in MATLAB software. The percentage drug release of predicted formulation matched with the manufactured formulation using the similarity factor (f2), which evaluates network efficiency. The ANNs have enormous potential for rapidly optimizing pharmaceutical formulations with desirable performance characteristics.

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

In this paper, paper microfluidic channel fabricated by directly screen-printing of polydimethylsiloxane (PDMS) is proposed for paper spray mass spectrometry analysis of therapeutic drugs in the blood samples. Compared with traditional paper spray, PDMS-printed paper spray (PP-PS) allows fluid to flow to the tip of paper with less sample loss which significantly improved the signal intensity of target compounds in blood samples. As paper can reduce the matrix effect, PP-PS also has a greater advantage than electro-spray Ionization (ESI) when directly analyzing complex biological sample in terms of the detection efficiency. Linearity and limits of detection (LOD) were evaluated for five psychotropic drugs: olanzapine, quetiapine, 9-hydroxyrisperidone, clozapine, risperidone. As a result, PP-PS improved the signal intensity of the psychotropic drugs at a concentration of 250 ng/ml in blood samples by a factor of 2-5 times and lowered the relative standard deviation (RSD) by a factor of 2-5.6 times compared with traditional paper spray. And PP-PS also improved signal intensity by a factor of 9-33 times compared with ESI. Quantitative experiments of PP-PS mass spectrometry indicated that the linear range was 5-500 ng/ml and the LOD were improved by a factor of 5-71 times for all these drugs compared with traditional paper spray. In addition, PP-PS was applied to the home-made miniaturized mass spectrometer and the precursor ions of all five psychotropic drugs (250 ng/ml) in the mass spectrometry results were obtained as well. These could prove that PP-PS has the potential to analyze complex biological samples in application on the miniaturized mass spectrometer which can be used outside the laboratory.

UNASSIGNED: Antipsychotics are widely used in the elderly due to the high prevalence of neuropsychiatric associated with dementia.
UNASSIGNED: To analyze potential disparities in antipsychotic use in the general population of Gipuzkoa by socioeconomic status (SES) and diagnosis of Alzheimer\'s disease and related dementia (ADRD) adjusting for somatic and psychiatric comorbidities, age, and sex.
UNASSIGNED: A retrospective observational study was carried out in all the 221,777 individuals over 60 years of age (Gipuzkoa, Spain) to collect diagnosis of ADRD, the Charlson Comorbidity Index, and psychiatric comorbidities considering all primary, outpatient, emergency and inpatient care episodes and first- and second-generation antipsychotics, and sociodemographic variables, namely, age, sex, SES and living in a nursing home. Logistic regression was used for multivariate statisticalanalysis.
UNASSIGNED: Use of any antipsychotic was greater in women, individuals over 80 years old, living in a nursing home, with a diagnosis of dementia, somatic and psychiatric comorbidities, and low SES. Quetiapine was the most used drug. The likelihood of any antipsychotic use was significantly associated with low SES (odds ratio [OR]: 1.60; confidence interval [CI]: 1.52-1.68), age over 80 years (OR: 1.56; CI: 1.47-1.65), institutionalization (OR: 12.61; CI: 11.64-13.65), diagnosis of dementia (OR: 10.18; CI: 9.55-10.85) and the comorbidities of depression (OR: 3.79; CI: 3.58-4.01) and psychosis (OR: 4.96; CI: 4.64-5.30).
UNASSIGNED: The greater levels of antipsychotic use and institutionalization in people of low SES indicate inequity in the management of neuropsychiatric symptoms. Increasing the offer of non-pharmacological treatments in the health system might help reduce inequity.

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

Voltage-dependent K+ (Kv) channels play an important role in restoring the membrane potential to its resting state, thereby maintaining vascular tone. In this study, native smooth muscle cells from rabbit coronary arteries were used to investigate the inhibitory effect of quetiapine, an atypical antipsychotic agent, on Kv channels. Quetiapine showed a concentration-dependent inhibition of Kv channels, with an IC50 of 47.98 ± 9.46 μM. Although quetiapine (50 μM) did not alter the steady-state activation curve, it caused a negative shift in the steady-state inactivation curve. The application of 1 and 2 Hz train steps in the presence of quetiapine significantly increased the inhibition of Kv current. Moreover, the recovery time constants from inactivation were prolonged in the presence of quetiapine, suggesting that its inhibitory action on Kv channels is use (state)-dependent. The inhibitory effects of quetiapine were not significantly affected by pretreatment with Kv1.5, Kv2.1, and Kv7 subtype inhibitors. Based on these findings, we conclude that quetiapine inhibits Kv channels in both a concentration- and use (state)-dependent manner. Given the physiological significance of Kv channels, caution is advised in the use of quetiapine as an antipsychotic due to its potential side effects on cardiovascular Kv channels.