RESUMO
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. OBJECTIVES: 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. CONCLUSION: 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.
Assuntos
Antipsicóticos , Ansiedade , Depressão , Esquizofrenia , Humanos , Esquizofrenia/epidemiologia , Masculino , Feminino , Adulto , Depressão/epidemiologia , Pessoa de Meia-Idade , Ansiedade/epidemiologia , China/epidemiologia , Prevalência , Antipsicóticos/uso terapêutico , Comorbidade , Psicologia do Esquizofrênico , Adulto Jovem , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Fumarato de Quetiapina/uso terapêuticoRESUMO
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.
Assuntos
Liberação Controlada de Fármacos , Redes Neurais de Computação , Comprimidos , Comprimidos/química , Excipientes/química , Preparações de Ação Retardada/química , Fumarato de Quetiapina/química , Fumarato de Quetiapina/farmacocinética , Fumarato de Quetiapina/administração & dosagem , Química Farmacêutica/métodosRESUMO
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.
Assuntos
Dimetilpolisiloxanos , Espectrometria de Massas , Papel , Humanos , Dimetilpolisiloxanos/química , Espectrometria de Massas/métodos , Limite de Detecção , Clozapina/sangue , Risperidona/sangue , Fumarato de Quetiapina/sangue , Palmitato de Paliperidona/sangue , Olanzapina/sangue , Psicotrópicos/sangue , ImpressãoRESUMO
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.
Assuntos
Antipsicóticos , Famotidina , Fumarato de Quetiapina , Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Feminino , Famotidina/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/uso terapêutico , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Evolução FatalRESUMO
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 ESCAPETRD 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 (KaplanMeier 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.
Assuntos
Preparações de Ação Retardada , Transtorno Depressivo Resistente a Tratamento , Ketamina , Sprays Nasais , Fumarato de Quetiapina , Humanos , Fumarato de Quetiapina/administração & dosagem , Fumarato de Quetiapina/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/uso terapêutico , Masculino , Feminino , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Preparações de Ação Retardada/administração & dosagem , Pessoa de Meia-Idade , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Administração Intranasal , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Resultado do TratamentoAssuntos
Antipsicóticos , Transtorno Bipolar , Síndrome da Ardência Bucal , Fumarato de Quetiapina , Humanos , Fumarato de Quetiapina/uso terapêutico , Fumarato de Quetiapina/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Síndrome da Ardência Bucal/tratamento farmacológico , Antipsicóticos/administração & dosagem , Feminino , Pessoa de Meia-Idade , Masculino , Resultado do TratamentoRESUMO
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.
Assuntos
Potenciais de Ação , Canais de Cálcio Tipo L , Ventrículos do Coração , Contração Miocárdica , Miócitos Cardíacos , Fumarato de Quetiapina , Animais , Fumarato de Quetiapina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/citologia , Ratos , Potenciais de Ação/efeitos dos fármacos , Masculino , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Ratos Sprague-Dawley , Antipsicóticos/farmacologia , Relação Dose-Resposta a Droga , Cálcio/metabolismoRESUMO
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.
Assuntos
Antipsicóticos , Vasos Coronários , Músculo Liso Vascular , Miócitos de Músculo Liso , Bloqueadores dos Canais de Potássio , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Fumarato de Quetiapina , Fumarato de Quetiapina/farmacologia , Animais , Coelhos , Antipsicóticos/farmacologia , Antipsicóticos/toxicidade , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Vasos Coronários/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Masculino , Relação Dose-Resposta a Droga , Potenciais da Membrana/efeitos dos fármacos , Células CultivadasRESUMO
AIMS: Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders. METHODS: This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy. RESULTS: Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk. CONCLUSION: Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.
Assuntos
Antimaníacos , Antipsicóticos , Transtorno Bipolar , Pontuação de Propensão , Fumarato de Quetiapina , Ácido Valproico , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/mortalidade , Antipsicóticos/uso terapêutico , Antipsicóticos/efeitos adversos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Ácido Valproico/uso terapêutico , Antimaníacos/uso terapêutico , Estudos de Coortes , Fumarato de Quetiapina/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Olanzapina/uso terapêutico , Hong Kong/epidemiologia , Risperidona/uso terapêutico , Risperidona/efeitos adversos , Lítio/uso terapêutico , Causas de MorteRESUMO
BACKGROUND: Cadmium (Cd) is a heavy metal with extremely harmful toxic effects on the brain. Quetiapine (QTP) has unique neuroprotective effects with anti-inflammatory and antioxidant actions. However, its neuroprotective effect against Cd-induced neurotoxicity has not been previously studied. METHODS: QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg. RESULTS: In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and ß-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1ß and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels. CONCLUSION: In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.
Assuntos
Cádmio , Inflamação , Estresse Oxidativo , Piroptose , Fumarato de Quetiapina , Estresse Oxidativo/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Cádmio/toxicidade , Fumarato de Quetiapina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismoRESUMO
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.
Assuntos
Antipsicóticos , Clozapina , Alucinações , Doença de Parkinson , Piperidinas , Fumarato de Quetiapina , Humanos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Clozapina/efeitos adversos , Clozapina/administração & dosagem , Clozapina/farmacologia , Alucinações/tratamento farmacológico , Alucinações/etiologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Piperidinas/administração & dosagem , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/farmacologia , Fumarato de Quetiapina/administração & dosagem , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/efeitos adversosRESUMO
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.
Assuntos
Antipsicóticos , Transtornos Psicóticos , Humanos , Antipsicóticos/uso terapêutico , Feminino , Masculino , Transtornos Psicóticos/tratamento farmacológico , Adulto , Aripiprazol/uso terapêutico , Risperidona/uso terapêutico , Adulto Jovem , Hospitalização/estatística & dados numéricos , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Fumarato de Quetiapina/uso terapêuticoRESUMO
Importance: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective: To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients' health outcomes. Design, Setting, and Participants: This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions: PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main Outcomes and Measures: The primary outcome of this analysis was patients' total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results: Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84â¯881 patients with dementia living in nursing homes and 261â¯288 community-dwelling patients with dementia were attributed to these PCPs. There were 92â¯874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64â¯242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and Relevance: This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care. Trial Registration: ClinicalTrials.gov Identifier: NCT05172687.
Assuntos
Antipsicóticos , Demência , Prescrição Inadequada , Fumarato de Quetiapina , Humanos , Demência/tratamento farmacológico , Demência/psicologia , Antipsicóticos/uso terapêutico , Feminino , Masculino , Idoso , Fumarato de Quetiapina/uso terapêutico , Prescrição Inadequada/estatística & dados numéricos , Idoso de 80 Anos ou mais , Padrões de Prática Médica/estatística & dados numéricos , Estados Unidos , Medicare , Cognição/efeitos dos fármacosRESUMO
Delirium often goes unrecognized in neonates and children because of lack of experience in evaluating behavior and cognition, insufficient awareness of the prevalence, and nondistinctive symptoms in this population. Although there are increasing reports of the presence of delirium in neonates, there are little data to guide the pharmacologic treatment in this population. In this retrospective single-center case series, we present our experience using quetiapine to treat delirium in 9 medically complex neonates. Based on an extensive literature review, expert opinion, and institutional experience, we propose an approach for monitoring and treating delirium in neonates and infants.
Assuntos
Delírio , Unidades de Terapia Intensiva Neonatal , Fumarato de Quetiapina , Humanos , Delírio/tratamento farmacológico , Delírio/diagnóstico , Recém-Nascido , Masculino , Feminino , Estudos Retrospectivos , Fumarato de Quetiapina/uso terapêutico , Antipsicóticos/uso terapêutico , LactenteRESUMO
PURPOSE: Τhe aim of the present study was to investigate the use of vitreous humor as an alternative biological material in forensic toxicology for the determination of quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine. The distribution of these substances in vitreous humor was studied by determining and correlating their concentrations in vitreous humor with the respective concentrations in blood. METHODS: During this study, a method for the determination of these substances was developed, validated and applied to postmortem samples obtained from 16 relative forensic cases. The sample preparation procedure included the isolation of the analytes from vitreous humor and blood samples using solid-phase extraction, with Bond Elut LRC C18 columns followed by derivatization with BSTFA with 1% TMCS prior to GC/MS analysis. RESULTS: The developed method is characterized by a dynamic range of 10.0-1000.0 ng/mL (R2 ≥ 0.991) for the three substances, with a limit of detection and quantification of 3.0 and 10.0 ng/mL, respectively. Accuracy and precision were below 8.09% and 8.99%, respectively, for both biological materials, while absolute recovery for the three substances was greater than 81%. According to the results, quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine are easily distributed in vitreous humor. CONCLUSION: The results of the study indicate the usefulness of vitreous humor in toxicological analysis for the determination of these substances, especially when the traditional biological materials are not available. The levels of quetiapine and its metabolites in vitreous humor as well as the vitreous humor to blood concentration ratios can provide important information for a more thorough toxicological investigation of forensic cases.
Assuntos
Antipsicóticos , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Fumarato de Quetiapina , Extração em Fase Sólida , Corpo Vítreo , Corpo Vítreo/química , Corpo Vítreo/metabolismo , Corpo Vítreo/efeitos dos fármacos , Fumarato de Quetiapina/farmacocinética , Fumarato de Quetiapina/análise , Humanos , Toxicologia Forense/métodos , Antipsicóticos/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Limite de Detecção , Feminino , Adulto , Pessoa de Meia-Idade , DibenzotiazepinasRESUMO
Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.
Assuntos
Antipsicóticos , Liberação Controlada de Fármacos , Grafite , Nanocompostos , Polietilenoglicóis , Fumarato de Quetiapina , Grafite/química , Polietilenoglicóis/química , Fumarato de Quetiapina/farmacocinética , Fumarato de Quetiapina/química , Fumarato de Quetiapina/administração & dosagem , Antipsicóticos/química , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Nanocompostos/química , Animais , Administração Intranasal , Portadores de Fármacos/químicaRESUMO
Quetiapine hemifumarate (QF) delivery to the CNS via conventional formulations is challenging due to poor solubility and lower oral bioavailability (9 %). Similarly, many other second-generation antipsychotics, such as olanzapine, clozapine, and paliperidone, have also shown low oral bioavailability of <50 %. Hence, the present work was intended to formulate QF-loaded biodegradable PLGA-NPs with appropriate surface charge modification through poloxamer-chitosan and investigate its targeting potential on RPMI-2650 cell lines to overcome the limitations of conventional therapies. QF-loaded poloxamer-chitosan-PLGA in-situ gel (QF-PLGA-ISG) was designed using emulsification and solvent evaporation techniques. Developed QF-PLGA-ISG were subjected to evaluation for particle size, PDI, zeta potential, ex-vivo mucoadhesion, entrapment efficiency (%EE), and drug loading, which revealed 162.2 nm, 0.124, +20.5 mV, 52.4 g, 77.5 %, and 9.7 %, respectively. Additionally, QF-PLGA formulation showed >90 % release within 12 h compared to 80 % of QF-suspension, demonstrating that the surfactant with chitosan-poloxamer polymers could sustainably release medicine across the membrane. Ex-vivo hemolysis study proved that developed PLGA nanoparticles did not cause any hemolysis compared to negative control. Further, in-vitro cellular uptake and transepithelial permeation were assessed using the RPMI-2650 nasal epithelial cell line. QF-PLGA-ISG not only improved intracellular uptake but also demonstrated a 1.5-2-fold increase in QF transport across RPMI-2650 epithelial monolayer. Further studies in the EpiNasal™ 3D nasal tissue model confirmed the safety and efficacy of the developed QF-PLGA-ISG formulation with up to a 4-fold increase in transport compared to plain QF after 4 h. Additionally, histological reports demonstrated the safety of optimized formulation. Finally, favorable outcomes of IN QF-PLGA-ISG formulation could provide a novel platform for safe and effective delivery of QF in schizophrenic patients.
Assuntos
Administração Intranasal , Quitosana , Portadores de Fármacos , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fumarato de Quetiapina , Quitosana/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Fumarato de Quetiapina/farmacocinética , Fumarato de Quetiapina/administração & dosagem , Fumarato de Quetiapina/química , Fumarato de Quetiapina/farmacologia , Humanos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Animais , Linhagem Celular , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacosAssuntos
Quimioterapia Combinada , Fluoxetina , Priapismo , Fumarato de Quetiapina , Trazodona , Humanos , Masculino , Trazodona/administração & dosagem , Trazodona/efeitos adversos , Priapismo/induzido quimicamente , Fluoxetina/efeitos adversos , Fluoxetina/administração & dosagem , Fumarato de Quetiapina/efeitos adversos , Pessoa de Meia-Idade , Antipsicóticos/efeitos adversos , Antipsicóticos/administração & dosagemRESUMO
INTRODUCTION: Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential rapid drug metabolism underlying low dose-adjusted serum concentration (CD) of non-clozapine atypical antipsychotics preceding clozapine treatment. METHODS: Patients using non-clozapine, atypical antipsychotics (aripiprazole, risperidone, olanzapine, or quetiapine) within 1 year before starting clozapine were included in this study from a therapeutic drug monitoring service in Oslo, Norway, between 2005 and 2023. Patients were assigned into low CD (LCD) and normal CD (NCD) subgroups. Using a reference sample with 147,964 antipsychotic measurements, LCD was defined as CDs below the 25th percentile, while patients with NCD exhibited CDs between the 25th and 75th percentile of the respective reference measurements. Metabolic ratios, doses, and frequency of subtherapeutic levels of non-clozapine antipsychotics were compared between LCD and NCD groups. RESULTS: Preceding clozapine treatment, 110 out of 272 included patients (40.4%) were identified with LCD. Compared with the NCD group, LCD patients exhibited higher metabolic ratios of olanzapine (1.5-fold; p < 0.001), quetiapine (3.0-fold; p < 0.001), and risperidone (6.0-fold; p < 0.001). Metabolic ratio differences were independent of smoking and CYP2D6 genotype for olanzapine (p = 0.008) and risperidone (p = 0.016), respectively. Despite higher doses of olanzapine (1.25-fold; p = 0.054) and quetiapine (1.6-fold; p = 0.001) in LCD versus NCD patients, faster metabolism among the former was accompanied by higher frequencies of subtherapeutic levels of olanzapine (3.3-fold; p = 0.044) and quetiapine (1.8-fold; p = 0.005). CONCLUSION: LCD and associated rapid metabolism of non-clozapine antipsychotics is frequent before starting clozapine treatment. For olanzapine and quetiapine, this is associated with significantly increased risk of having subtherapeutic concentrations.
Assuntos
Antipsicóticos , Clozapina , Monitoramento de Medicamentos , Humanos , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Monitoramento de Medicamentos/métodos , Noruega , Esquizofrenia/tratamento farmacológico , Esquizofrenia/sangue , Esquizofrenia Resistente ao Tratamento/tratamento farmacológico , Fumarato de Quetiapina/administração & dosagemRESUMO
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.