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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. [ABSTRACT FROM AUTHOR]

Over the past decade, increasing off‐label use of quetiapine has been reported worldwide from various sources. We wanted to investigate how this is reflected in therapeutic drug monitoring (TDM) data. Requisitions for serum concentration measurements of quetiapine from a TDM service in Central Norway during 2001–2019 were obtained and analysed for age, gender, trends in quetiapine doses, serum concentrations and indicators of diagnoses. There were 19 759 requisitions from 7459 individuals. Daily doses of quetiapine decreased by 24 mg per year (95% CI: −25.61 to −21.48, p < 0.001, N = 4505). A corresponding decrease in quetiapine serum concentrations was not seen. The proportion of requisitions with diagnoses indicating reimbursable use was 13% for the whole study period. Mean daily doses were slightly higher in the reimbursable group, but declined over time in these samples, as well. To our understanding, these results signal a trend towards lower prescribed doses of quetiapine, possibly reflecting drug repurposing and/or off‐label use. The discrepancy in the decrease of doses versus serum concentrations may reflect the intake of higher doses than prescribed and/or inappropriate TDM sampling. Our findings show that TDM data have limitations when it comes to making inferences about the use of quetiapine based on serum concentrations and clinical information on the requisitions. [ABSTRACT FROM AUTHOR]

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

Rationale: Evidence of the effects of chronic caffeine (CAFF)-containing beverages, alone or in combination with agomelatine (AGO) or quetiapine (QUET), on electroencephalography (EEG), which is relevant to cognition, epileptogenesis, and ovarian function, remains lacking. Estrogenic, adenosinergic, and melatonergic signaling is possibly linked to the dynamics of these substances. Objectives: The brain and ovarian effects of CAFF were compared with those of AGO + CAFF and QUET + CAFF. The implications of estrogenic, adenosinergic, and melatonergic signaling and the brain-ovarian crosstalk were investigated. Methods: Adult female rats were administered AGO (10 mg/kg), QUET (10 mg/kg), CAFF, AGO + CAFF, or QUET + CAFF, once daily for 8 weeks. EEG, estrous cycle progression, and microstructure of the brain and ovaries were examined. Brain and ovarian 17β-estradiol (E2), antimullerian hormone (AMH), estrogen receptor alpha (E2Rα), adenosine receptor 2A (A2AR), and melatonin receptor 2 (MT2R) were assessed. Results: CAFF, alone or combined with AGO or QUET, reduced the maximum EEG peak, which was positively linked to ovarian E2Rα, negatively correlated to cortical neurodegeneration and ovarian MT2R, and associated with cystic ovaries. A large corpus luteum emerged with AGO + CAFF and QUET + CAFF, antagonizing the CAFF-mediated increased ovarian A2AR and reduced cortical E2Rα. AGO + CAFF provoked TTP delay and increased ovarian AMH, while QUET + CAFF slowed source EEG frequency to δ range and increased brain E2. Conclusions: CAFF treatment triggered brain and ovarian derangements partially antagonized with concurrent AGO or QUET administration but with no overt affection of estrus cycle progression. Estrogenic, adenosinergic, and melatonergic signaling and brain-ovarian crosstalk may explain these effects. [ABSTRACT FROM AUTHOR]

Background: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case–control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. Methods: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000–2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic–severe sepsis associations. Results: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin–angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. Conclusion: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication. [ABSTRACT FROM AUTHOR]

Background: In the population of patients in the intensive care unit (ICU), most studies compared the use of atypical antipsychotics, such as quetiapine, with the use of traditional haloperidol in patients with delirium of various forms and etiologies. The role of such agents in patients with hyperactive delirium is not fully understood. This study compares the effectiveness of quetiapine with haloperidol in treating the hyperactive form of delirium in terms of their effects on the Delirium Rating Scale-Revised-98 (DRS-R-98), length of stay in the ICU, and mortality in critically ill patients. Methods: One hundred adult patients diagnosed with hyperactive delirium were randomly assigned to receive either oral quetiapine (25–50 mg/day) or haloperidol (1–2 mg/day). The response, defined as "a DRS-R-98 severity score reduction from baseline of 50% or more" and a DRS-R-98 severity score of 12 or less without relapse, was the primary outcome. Results: The mean age of all patients was 68 ± 6 years. The study population's overall response rate was 92%. Response rates for the two groups were remarkably equal (p = 0.609). Secondary outcomes were comparable in both groups, such as ICU mortality (p = 0.496), in-hospital mortality (p = 0.321), in-hospital stay (p = 0.310), and the need for mechanical ventilation (p > 0.99). But the quetiapine group showed a statistically reduced mean ICU stay (10.1 ± 2.0 vs. 11.7 ± 2.6 days, p = 0.018) and increased sleeping hours per night (p = 0.001). Conclusions: Quetiapine may be equally as effective as haloperidol in treating the symptoms of hyperactive delirium in critically ill patients, with no mortality benefit. [ABSTRACT FROM AUTHOR]

Introduction Sleep-related disorders are associated with pain, fatigue, and deficits in cognitive performance, which may interfere with successful rehabilitation. The study objectives were to (1) quantify outpatient prescriptions for insomnia medications during the first year following combat-related amputations, (2) examine longitudinal changes in prescriptions for insomnia medications, and (3) analyze patient characteristics associated with prescriptions for insomnia medications. Material and Methods This was a retrospective study of DoD casualty records from the Expeditionary Medical Encounter Dataset and prescriptions for outpatient medications from the Pharmacy Data Transaction Service. Patients were a total of 1,651 U.S. service members who sustained major limb amputations in Operations Iraqi and Enduring Freedom from 2001 through 2017 and had outpatient prescriptions for any medication during the first year postinjury. Prescriptions for medications recommended for insomnia were low-dose antidepressants, anxiolytic sedatives, benzodiazepines, melatonin receptor agonist, and low-dose quetiapine. These prescription medications were analyzed by medication type, postinjury time, and patient characteristics during the first year postinjury. Results During the first year postinjury, 78% of patients (1,291 of 1,651) had outpatient prescriptions for insomnia medications, primarily anxiolytic sedative drugs (e.g. zolpidem), averaging a total of 86 prescription days (median = 66). The prevalence of these prescriptions declined substantially during the first year, from 57% of patients during the first quarter to 28% during the fourth quarter postinjury. In univariate analyses, multiple patient characteristics, including high Injury Severity Score, continued opioid and non-opioid analgesic prescriptions, and diagnoses of chronic pain, mood disorder, and posttraumatic stress disorder, were significantly associated with higher prevalence and duration of outpatient prescriptions for insomnia medications. Conclusions The present results indicate a high prevalence of outpatient prescriptions for insomnia medications following combat-related amputations, a prevalence that is substantially higher than previously reported among active duty personnel. These findings can inform DVA/DoD guidelines for amputation care and insomnia among military subpopulations. The results highlight the need for more research on the treatment of insomnia during early postinjury rehabilitation among patients who sustained serious combat injuries. [ABSTRACT FROM AUTHOR]

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

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

This study aims to describe the patterns and trends in antipsychotic prescription among Dutch youth before and during the corona virus disease 2019 (COVID-19) pandemic (between 2017 and 2022). The study specifically aims to determine whether there has been an increase or decrease in antipsychotic prescription among this population, and whether there are any differences in prescription patterns among different age and sex groups. The study utilized the IADB database, which is a pharmacy prescription database containing dispensing data from approximately 120 community pharmacies in the Netherlands, to analyze the monthly prevalence and incidence rates of antipsychotic prescription among Dutch youth before and during the pandemic. The study also examined the prescribing patterns of the five most commonly used antipsychotics and conducted an autoregressive integrated moving average (ARIMA) analysis using data prior to the pandemic, to predict the expected prevalence rate during the pandemic. The prescription rate of antipsychotics for Dutch youth was slightly affected by the pandemic, with a monthly prevalence of 4.56 [4.50–4.62] per 1000 youths before COVID-19 pandemic and 4.64 [4.59–4.69] during the pandemic. A significant increase in prevalence was observed among adolescent girls aged 13–19 years. The monthly incidence rate remained stable overall, but rose for adolescent girls aged 13–19 years. Aripiprazole, and Quetiapine had higher monthly prevalence rates during the pandemic, while Risperidone and Pipamperon had lower rates. Similarly, the monthly incidence rates of Aripiprazole and Olanzapine went up, while Risperidone went down. Furthermore, the results from the ARIMA analysis revealed that despite the pandemic, the monthly prevalence rate of antipsychotic prescription was within expectation. The findings of this study suggest that there has been a moderate increase in antipsychotic prescription among Dutch youth during the COVID-19 pandemic, particularly in adolescent females aged 13–19 years. However, the study also suggests that factors beyond the pandemic may be contributing to the rise in antipsychotic prescription in Dutch youth. [ABSTRACT FROM AUTHOR]

Background: Although guidelines recommend twice daily (BID) dosing of quetiapine for treatment of intensive care unit (ICU) delirium in most patients, once daily dosing at bedtime (HS) is commonly prescribed to reduce daytime somnolence. No studies have evaluated differences in outcomes. Objectives: To determine if twice daily vs bedtime dosing of quetiapine reduces the duration of ICU delirium. Methods: Retrospective analysis of ICU patients treated with twice daily vs bedtime dosing of quetiapine for ICU delirium. Health records were analyzed between January 1, 2017, and December 31, 2021. Exclusions included alcohol withdrawal, history of psychiatric conditions requiring medication, receipt of <24 hours of therapy, alternative dosing schedules, and death or transfer from the ICU <24 hours after beginning quetiapine. The primary outcome was recovery of delirium per Confusion Assessment Method (CAM-ICU). Secondary outcomes included lengths of stay, mechanical ventilation duration, in-hospital death, and QTc prolongation. Results: Baseline characteristics differed for sex (30.4% vs 61.1% female) and admission diagnosis (39% vs. 17% COVID-19, respectively). Time to delirium recovery was 3.5 days for BID vs 2.5 days for QHS dosing (P =.484). Secondary outcomes of ICU (16 vs. 19 days) and hospital (22 vs. 25 days) lengths of stay, duration of mechanical ventilation (10 vs. 14), delirium recovery (70% vs. 56%), in-hospital death (61% vs. 50%), and QTc prolongation did not differ significantly between groups. Conclusions: Twice daily vs bedtime dosing of quetiapine did not significantly alter delirium outcomes, suggesting similar efficacy. Larger sample sizes are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Good adherence to antipsychotic therapy helps prevent relapses in first-episode psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts, to emulate a target trial comparing antipsychotics, with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from the European First Episode Schizophrenia Trial, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse-probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone were 61.5% (95% CI, 52.5-70.6), 73.5% (95% CI, 60.5-84.9), 76.8% (95% CI, 67.2-85.3), 58.4% (95% CI, 40.4-77.4), 76.5% (95% CI, 62.1-88.5), and 74.4% (95% CI, 67.0-81.2), respectively. Compared with aripiprazole, the 12-month risk differences were -15.3% (95% CI, -30.0 to 0.0) for olanzapine, -12.8% (95% CI, -25.7 to -1.0) for risperidone, and 3.0% (95% CI, -21.5 to 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration sufficed to remove confounding for these clinical questions. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

Objective: Morbid hunger and hyperphagia (MHH) is a rare neurological disorder that can manifest following damage to the right frontal and temporal lobes. It can lead to detrimental short and long-term complications such as electrolyte imbalances, obesity, and cardiovascular diseases. This report details the case of a young male patient who developed MHH five months post-traumatic brain injury. Method: Single-case report. The patient exhibited colossal appetite, overeating, food-demanding behavior, and rapid weight gain. The prescription of quetiapine to manage his visual and auditory hallucinations was suspected of exacerbating the hyperphagia. A comprehensive, multidisciplinary rehabilitation approach was implemented, encompassing a meticulous dietary regime, environmental modifications, behavioral management, physical activities, therapeutic exercises, and pharmacological interventions, which included switching the anti-psychotics and introducing low-dose escitalopram. Results: Over the course of 6 months, the MHH gradually subsided, and the patient achieved the target bodyweight. The Glasgow Outcome Scale-Extended improved from 3 to 5. Conclusion: This is the first report on the use of escitalopram to manage secondary eating disorders. Our findings underscore the necessity to formally catalog and recognize disorders like MHH in diagnostic classifications to facilitate the systematic study of their pathophysiology, natural history, prognosis, and management strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Quetiapine (QTP) is a moderately water-soluble biopharmaceutical classification system (BCS) class II antipsychotic drug used to treat schizophrenia. Carboxymethyl chitosan (CMC) microspheres were prepared using a co-precipitation approach. The Quetiapine was translocated to the brain through a nasal route using carboxymethyl chitosan-calcium carbonate (CMC-CaCO3) hybrid microspheres. During this process, optimization controlled the size of the microspheres by controlling the volume of solution, precipitating agent, and concentration ratios of the precursors. The optimized batch showed a narrow size distribution with high stability in the dispersed phase as characterized by dynamic light scattering. Preliminary characterization revealed crosslinking formation between the carboxymethyl groups of chitosan and the CaCO3 may be responsible for the spherical structure. The preliminary evaluations were done with Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and UV visible spectroscopy (UV-Vis). The surface morphology was assessed by scanning electron microscopy that showed the microscale range of the spherical-shaped particles. The ex-vivo mucoadhesive studies suggested a high binding affinity toward mucin, having a sustained release effect for up to 8 h. [ABSTRACT FROM AUTHOR]

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. Case presentation: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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, Q1 = 15.5; Q3 = 90.5 vs. 92.0 ng/mL, Q1 = 52.3; Q3 = 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. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care. [ABSTRACT FROM AUTHOR]

Antipsychotics are frequently used for inpatients with alcohol withdrawal syndromes (AWS). While there is evidence on the effects of these medications in other settings there is little data on the mortality rate associated with these drugs for the treatment of AWS) We utilized the national COSMOS Epic database to identify inpatients with AWS. We then assessed the mortality rate for adult patients with or without the use of anti-psychotics along with subsets of patients based on age, gender, race, and ethnicity. We identified 233,821 patients of whom 26% received antipsychotic agents. The mortality rate was 1.5%. Patients aged 60 or over and those who received typical antipsychotic agents had a higher mortality rate. The use of typical antipsychotic agents is associated with a higher mortality rate. The use of any antipsychotic agent in patients aged 60 or over is associated with an increased mortality rate. Further study of this effect is warranted. [ABSTRACT FROM AUTHOR]

Background: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice. Methods: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it"). Physicians who were unfamiliar with a management option were deemed to have never prescribed or performed it. Results: Regarding medication, most physicians were familiar with novel hypnotics. Suvorexant was the most used hypnotic, followed by lemborexant and ramelteon. These novel hypnotics averaged 4.8–5.4 points and 4.0–4.7 points for sleep onset and sleep maintenance insomnia, respectively. By contrast, most benzodiazepines were seldom used below two points. Regarding psychotherapy, only approximately 40% of the physicians were familiar with cognitive behavioral therapy for insomnia (CBT-I) and they rarely implemented it, at an average of 1.5–1.6 points. More physicians were familiar with single-component psychotherapies (i.e., relaxation, sleep restriction therapy, and stimulus control) compared to CBT-I, and 48–74% of them implemented it slightly more often, with scores ranging from 2.6 to 3.4 points. Conclusion: This study suggests that Japanese primary care physicians seldom use CBT-I to treat insomnia. In addition, they use novel sleep medications more frequently than benzodiazepines in terms of pharmacotherapy. The use and availability of CBT-I in Japanese primary care might be facilitated by: educating primary care physicians, implementing brief or digital CBT-I, and/or developing collaborations between primary care physicians and CBT-I specialists. [ABSTRACT FROM AUTHOR]

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

Purpose: Lamotrigine was previously reported to reduce serum concentration of quetiapine. The aim of this study was to investigate whether lamotrigine dose or quetiapine formulation was of importance for the drug interaction. Methods: Patients combining lamotrigine with quetiapine (cases) were included retrospectively from a routine therapeutic drug monitoring (TDM) service, as were a control group of patients using quetiapine without any interacting drugs. The case and control groups were divided into groups using immediate release (IR) and extended release (XR) quetiapine. The case group was further split into high-dose (> 200 mg/day) and low-dose (≤ 200 mg/day) lamotrigine users. Quetiapine concentration-to-dose (C/D) ratio and metabolite-to-parent ratio (MPR) were compared between the control group and dose-separated case groups using ANOVA test and t-tests. Results: In total, 406 patients were included. The mean C/D ratio of IR quetiapine was 46% lower in the high-dose lamotrigine group compared with the control group (P < 0.001), while no interaction effect was present in the low dose lamotrigine group (P = 0.7). Regardless of lamotrigine dose, there was no difference in quetiapine C/D ratio for patients using the XR formulation (P = 0.4). The quetiapine MPR was unaffected regardless of formulation and lamotrigine dose (P ≥ 0.06). Conclusion: The effect of lamotrigine in reducing quetiapine concentration is only significant for patients using quetiapine IR tablets who are treated with lamotrigine doses > 200 mg/day. Because of high variability in the interaction effect, TDM of quetiapine should be recommended during co-prescription of high-dose lamotrigine. [ABSTRACT FROM AUTHOR]

Objective: The study retrospectively evaluated the effects of quetiapine on sleep in primary insomnia and neurodegenerative diseases using polysomnographic data. Materials and Methods: Between January 1, 2010, and June 1, 2023, the records of 49 patients who were followed up in the sleep outpatient clinic of the neurology department of our hospital and who underwent polysomnography examination were retrospectively reviewed. Patients aged between 18 and 65 years with primary insomnia and neurodegenerative diseases were included in the study. Results: The mean age of 49 patients (26 females and 23 males) were 56.67 years. The mean quetiapine dose was 59.37. Sleep latency, stage 1 (N1) duration, stage 2 (N2) duration, mean and minimum SO2 and apnea-hypopnea index were similar. Total sleep duration, stage 3 (N3) duration and rapid eye movement (REM) sleep duration were higher in neurodegenerative patients. N3 duration was shorter in patients with primary insomnia on quetiapine. Sleep duration and REM duration were longer in the neurodegenerative group and sleep latency was longer in primary insomnia in quetiapine users. Among quetiapine users, the N2 sleep percentage was higher and the nonREM 3 sleep percentage was lower in primary insomnia, whereas there was no difference in sleep percentages in neurodegenerative patients. Conclusion: Quetiapine is an atypical antipsychotic agent. It shortens sleep latency and decreases the percentage of REM sleep and wake time. It increases total sleep time, sleep efficiency, and N2 sleep. In this study, in primary insomnia patients using quetiapine, N3 sleep duration was shorter and sleep percentage was lower, whereas N2 sleep percentage was longer. There has been no placebo-controlled study of any antipsychotic drug for treating insomnia. [ABSTRACT FROM AUTHOR]

Background: International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice. Objectives: We aimed to describe the prevalence and patterns of antipsychotic use in delirium management with regard to best-practice recommendations. Primary outcomes investigated were prevalence of use, antipsychotic type, dosage and clinical indication. Methods: Eligibility criteria: studies of any design that examined antipsychotic use to manage delirium in adults in critical care, acute care, palliative care, rehabilitation, and aged care were included. Studies of patients in acute psychiatric care, with psychiatric illness or pre-existing antipsychotic use were excluded. Information sources: we searched five health databases on 16 August, 2023 (PubMed, CINAHL, Embase, APA PsycInfo, ProQuest Health and Medical Collection) using MeSH terms and relevant keywords, including 'delirium' and 'antipsychotic'. Risk of bias: as no included studies were randomised controlled trials, all studies were assessed for methodological quality using the Mixed Methods Appraisal Tool. Synthesis of results: descriptive data were extracted in Covidence and synthesised in Microsoft Excel. Results: Included studies: 39 studies published between March 2004 and August 2023 from 13 countries (n = 1,359,519 patients). Most study designs were retrospective medical record audits (n = 16). Synthesis of results: in 18 studies, participants' mean age was ≥65 years (77.79, ±5.20). Palliative care had the highest average proportion of patients with delirium managed with antipsychotics (70.87%, ±33.81%); it was lower and varied little between intensive care unit (53.53%, ±19.73%) and non-intensive care unit settings [medical, surgical and any acute care wards] (56.93%, ±26.44%) and was lowest in in-patient rehabilitation (17.8%). Seventeen different antipsychotics were reported on. In patients aged ≥65 years, haloperidol was the most frequently used and at higher than recommended mean daily doses (2.75 mg, ±2.21 mg). Other antipsychotics commonly administered were olanzapine (mean 11 mg, ±8.54 mg), quetiapine (mean 64.23 mg, ±43.20 mg) and risperidone (mean 0.97 mg, ±0.64 mg). Conclusions: The use of antipsychotics to manage delirium is strongly discouraged in international guidelines. Antipsychotic use in delirium care is a risk for adverse health outcomes and a longer duration of delirium, especially in older people. However, this study has provided evidence that clinicians continue to use antipsychotics for delirium management, the dose, frequency and duration of which are often outside evidence-based guideline recommendations. Clinicians continue to choose antipsychotics to manage delirium symptoms to settle agitation and maintain patient and staff safety, particularly in situations where workload pressures are high. Sustained efforts are needed at the individual, team and organisational levels to educate, train and support clinicians to prioritise non-pharmacological interventions early before deciding to use antipsychotics. This could prevent delirium and avert escalation in behavioural symptoms that often lead to antipsychotic use. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to verify the real‐world efficacy and safety of quetiapine fumarate extended‐release tablets (Bipresso® 50 mg and 150 mg; marketing authorization holder is KYOWA Pharmaceutical Industry Co., Ltd., Osaka, Japan) in patients with bipolar depression. Methods: We performed a post‐marketing surveillance with an observation period of 12 weeks. Results: In the safety analysis group (n = 345), adverse drug reactions (ADRs) occurred in 111 patients (32.17%). The most common ADRs (>1%) were somnolence in 55 patients (15.94%), akathisia in 11 (3.19%), dizziness in 10 (2.90%), weight increase in 6 (1.74%), thirst in 5 (1.45%), and hypersomnia, constipation, and nausea in 4 patients each (1.16%). The only severe ADR was one patient of suicidal ideation, and "longer time since the onset of the first episode" (p = 0.011) and "presence of complications" (p < 0.001) were identified as significant risk factors for the occurrence of ADRs. In the efficacy analysis group (n = 265), the average changes from baseline in the total Montgomery–Åsberg Depression Rating Scale (MADRS) score were −7.3 ± 8.8, −12.2 ± 10.7, −16.8 ± 12.7, and −13.2 ± 12.7 points after 4, 8, and 12 weeks, and at the last evaluation, respectively. The mean MADRS total score decrease had no significant association with maximum daily dose, diagnosis, and presence or absence of prior or concomitant treatment for bipolar disorder with mood stabilizers/antipsychotics/antidepressants. Conclusion: The efficacy of quetiapine fumarate extended‐release tablets was confirmed in clinical practice, and no new safety concerns or risks were identified. [ABSTRACT FROM AUTHOR]

Summary: Quetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses 'off‐label' in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps. [ABSTRACT FROM AUTHOR]

Quetiapine fumarate is an atypical antipsychotic drug to treat schizophrenia. It has poor oral bioavailability (9 %) owing to its extensive first-pass metabolism. In the present study, quetiapine nanoemulsion were formulated for brain targeting through the intranasal route. Ultrasonication method was employed for nanoemulsion preparation by employing water, Tween 20 and propylene glycol as the surfactant mixture (surfactant and co-surfactant mixture) and isopropyl myristate as oil. Rat models were used to examine the concentration of quetiapine in the brain and blood (plasma) following oral, intranasal and free medication administration. When compared to the intranasal-free drug and the oral route, intranasal nanoemulsion of quetiapine led to noticeably greater drug levels in the brain. The results showed that intranasal nanoemulsion, as opposed to intranasally or orally delivered free drug had a longer half-life in the brain. Hence, using intranasal quetiapine nanoemulsion to treat schizophrenia and bipolar disorder may be a novel way to handle this illness. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Individuals with bipolar disorders (BD) have heterogenic pre‐onset illness courses and responses to treatment. The pattern of illness preceding the diagnosis of BD may be a marker of future treatment response. Here, we examined associations between psychiatric morbidity preceding the diagnosis of BD and pharmacological treatment patterns in the 2 years following diagnosis.In this register‐based study, we included all patients with a diagnosis of BD attending Danish Psychiatric Services between January 1, 2012 and December 31, 2016. We examined the association between a diagnosis of substance use disorder, psychosis (other than schizophrenia or schizoaffective disorder), unipolar depression, anxiety/OCD, PTSD, personality disorder, or ADHD preceding BD and pharmacological treatment patterns following the diagnosis of BD (lithium, valproate, lamotrigine, antidepressants, olanzapine, risperidone, and quetiapine) via multivariable Cox proportional hazards regression adjusted for age, sex, and year of BD diagnosis.We included 9594 patients with a median age of 39 years, 58% of whom were female. Antidepressants, quetiapine, and lamotrigine were the most commonly used medications in BD and were all linked to prior depressive illness and female sex. Lithium was used among patients with less diagnostic heterogeneity preceding BD, while valproate was more likely to be used for patients with prior substance use disorder or ADHD.The pharmacological treatment of BD is linked to psychiatric morbidity preceding its diagnosis. Assuming that these associations reflect well‐informed clinical decisions, this knowledge may inform future clinical trials by taking participants' prior morbidity into account in treatment allocation. [ABSTRACT FROM AUTHOR]

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

Little is known about the rates of prediabetes and diabetes in those over the age of 35 years in UK early intervention for psychosis (EIP) services. In this article, the authors discuss their retrospective case note service evaluation of patients within an NHS EIP service where they evaluate the prevalence of prediabetes and diabetes in the 'over‐35' cohort, its monitoring and management. The 'over‐35' cohort represented a third of the EIP caseload and is a high‐risk group for prediabetes and diabetes. More research and innovative strategies are needed in terms of both lifestyle and pharmacological interventions in this patient population to reduce the risk of developing, and improve management of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Parkinson’s disease is the most common neurodegenerative disease. Until recently, the treatment was focused on dopamine deficiency and enabling patient activity. Much less attention was paid to the cognitive impairment and non-motor symptoms of the disease. Dementia, hallucinations and delusions are the most common cognitive disorders influencing a patient’s quality of life. Hallucinations are probably the most common and bothersome non-motoric symptom. This paper discusses the diagnosis and treatment of hallucinations with atypical antipsychotics and possible alternatives. A sensible approach for patients with hallucinations and delusions is suggested. [ABSTRACT FROM AUTHOR]

Objective: To determine antipsychotic utilisation patterns in Australian adults from 2005 to 2021, with a focus on on-label and off-label prescriptions. Methods: We examined antipsychotic dispensing trends in adults from 2005 to 2021 using a 10% sample of the Pharmaceutical Benefits Scheme (PBS) dataset, which contains patient-level information on medicines dispensed throughout Australia. The lack of diagnostic information in PBS was substituted by analysing BEACH (Bettering the Evaluation And Care of Health) dataset, a cross-sectional national survey from 2000 to 2016, consisting of data from general practitioner–patient encounters. Results: There were 5.6 million dispensings for 164,993 patients in PBS throughout this period; 69% patients had >1 dispensing, with a median of 6 per patient. Calculating the estimated period of exposure gave a total of 693,562 treatment episodes, with a median duration of 80 days. There were steady increases in both the incidence and prevalence of antipsychotic dispensings, mainly due to oral second-generation antipsychotics. The most commonly prescribed antipsychotics were quetiapine, olanzapine and risperidone, with a significant portion of patients receiving low-dose quetiapine without dose titration. Analysis of diagnostic indications from BEACH indicated that 27% of antipsychotic prescriptions were off-label for indications such as depression, dementia, anxiety and insomnia, at much lower prescribed daily dosages. Conclusion: The increasing prescribing and off-label use highlights concerns about chronic adverse effects caused by antipsychotics. The combined analysis of medication dispensings and the diagnostic indications for which they are prescribed is a novel approach and throws a spotlight on the need for additional monitoring of antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown. Objective: This study aimed to investigate the behavioral and cognitive effects of QET in both naïve and sleep-deprived rats. Materials and methods: Seven groups (n = 49) of male Wistar Albino rats were used in this study. SD was performed using the modified multiple platform technique in a water tank for 72 h. Our study consists of two experiments investigating the effect of QET on pre-pulse inhibition (PPI) of the acoustic startle reflex. The first experiment tested the effect of short- and long-term administration of QET on PPI response in non-sleeping (NSD) rats. The second experiment used 72 h REM sleep deprivation as a model for SD-induced impairment of the PPI response. Here, we tested the effect of QET on the % PPI of SD rats by short- and long-term intraperitoneal injection at the last 90 min of sleep SD and immediately subsequently tested for PPI. Results: 72 h SD impaired PPI, reduced startle amplitude, and attenuated the PPI% at + 4 dB, + 8 dB, and + 16 dB prepulse intensities. 10 mg/kg short and long-term QET administration completely improved sensorimotor gating deficit, increased startle amplitude, and restored the impaired PPI% at + 4 dB, + 8 dB, and + 16 dB after 72 h SD in rats. Conclusion: Our results showed short- and long-term administration of QET improved sensorimotor gating deficit in 72 h SD. Further research is required for the etiology of insomnia and the dose-related behavioral effects of QET. [ABSTRACT FROM AUTHOR]

Quetiapine use is on the rise, leading to a corresponding increase in acute intoxications, some of which have fatal outcomes. When assessing whole-blood quetiapine concentrations during forensic autopsies, interpretations are primarily based on toxicity data from studies of serum concentrations. To our knowledge, there are only two previous studies that have attempted to establish the ratio between whole blood and serum quetiapine concentrations with limited populations and high variability of results. Paired specimens of whole blood and serum from 16 quetiapine users recruited from the Psychiatric Clinic, St. Olav University Hospital were analyzed using LC–MS-MS. Quetiapine concentrations in both matrices were determined and compared. The mean blood:serum ratio of quetiapine was 0.74 (standard deviation (SD) = 0.05, 95% confidence interval (CI) 0.71–0.76, P  < 0.001), range 0.66–0.85. Simple linear regression showed strong linear correlation between quetiapine concentrations in the two matrices (B = 0.774, P  > 0.001, r  = 0.999). Our results imply that quetiapine occurs at lower concentrations within erythrocytes than in plasma. This is most likely due to a high degree of plasma protein binding. Other factors which may influence the distribution of quetiapine between these compartments are solubility, metabolism and passive or active efflux mechanisms. We did not observe any covariation between blood:serum ratios and serum concentrations. Quetiapine was consistently present at lower concentrations in whole blood than in serum. If so inclined to, a conversion factor of ∼0.7 may be considered for extrapolation of concentrations from serum to whole blood, at least in cases with therapeutic quetiapine concentration levels. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration–effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ. [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]

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]

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.

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]

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]

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]