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OBJECTIVES: To describe haematological adverse effects in adolescents with anorexia nervosa who are taking olanzapine. METHODS: Case series report. CASE REPORT: The reported cases (two female patients and one male) were found to have blood test abnormalities after starting olanzapine and to rapidly recover their platelet and neutrophil values after the drug was discontinued. Low haemoglobin values persisted longer than observed in other series. These abnormalities became more noticeable when the dose of olanzapine was increased to 5â¯mg/day (initial dose 2.5â¯mg/day). It should be noted that two of the patients already had values indicative of mild neutropenia before they started the antipsychotic drug, and that these worsened as they continued taking the drug. In one of the patients there was only a decrease in neutrophil values, as well as mild anaemia. CONCLUSIONS: This first case series of haematological abnormalities in adolescents with anorexia nervosa who are taking olanzapine found values corresponding to pancytopenia in two of the three cases reported. It would be worthwhile to consider heightening haematological surveillance in this population when starting treatment with olanzapine and rethinking our knowledge regarding the frequency of these side effects.
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Anorexia Nerviosa , Antipsicóticos , Benzodiazepinas , Olanzapina , Humanos , Olanzapina/efectos adversos , Olanzapina/administración & dosificación , Femenino , Adolescente , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Masculino , Benzodiazepinas/efectos adversos , Benzodiazepinas/administración & dosificación , Pancitopenia/inducido químicamente , Relación Dosis-Respuesta a DrogaRESUMEN
RESUMEN Objetivos: Describir los efectos adversos hematológicos en adolescentes con anorexia nerviosa que toman olanzapina. Métodos: Reporte de serie de casos. Reporte de caso: En los casos reportados (2 mujeresy1varón) se evidenciaron alteraciones de las series sanguíneas tras el inicio de olanzapina y una recuperación rápida de los valores de plaquetas y neutrófilos tras la suspensión del fármaco. Los valores bajos de hemoglobina persistieron más que en las otras series. Dichas alteraciones se hicieron más ostensibles al incrementarse la dosis de olanzapina a 5 mg/día (dosis inicial, 2,5mg/día). Cabe resaltar que antes del inicio del psicofármaco 2 de los pacientes ya tenían valores en la banda de la neutropenia leve, que fueron empeorando a medida que se instalaba el antipsicótico. En uno de los pacientes solo se redujeron los valores de neutrófilos junto con anemia leve. Conclusiones: Este es el primer reporte de casos de alteraciones hematológicas en adolescentes con anorexia nerviosa que toman olanzapina, y se hallaron valores de pancitopenia en 2 de los 3 casos estudiados. Se debería considerar una mayor vigilancia hematológica en dicha población al iniciar el tratamiento con olanzapina y replantear nuestros conocimientos en cuanto a la frecuencia de dichos efectos secundarios.
ABSTRAC Objectives: To describe haematological adverse effects in adolescents with anorexia nervosa who are taking olanzapine. Methods: Case series report. Case report: The reported cases (two female patients and one male) were found to have blood test abnormalities after starting olanzapine and to rapidly recover their platelet and neutrophil values after the drugwas discontinued. Low haemoglobin values persisted longer than observed in other series. These abnormalities became more noticeable when the dose of olanzapine was increased to 5 mg/day (initial dose 2.5mg/day). It should be noted that two of the patients already had values indicative of mild neutropenia before they started the antipsychotic drug, and that these worsened as they continued taking the drug. In one of the patients there was only a decrease in neutrophil values, as well as mild anaemia. Conclusions: This first case series of haematological abnormalities in adolescents with anorexia nervosa who are taking olanzapine found values corresponding to pancytopenia in two of the three cases reported. It would be worthwhile to consider heightening haematological surveillance in this population when starting treatment with olanzapine and rethinking our knowledge regarding the frequency of these side effects.
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Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics are poorly understood. The present study aimed to determine the differential and long-lasting changes in FosB distribution and DARPP-32 phosphorylation in the striatum and nucleus accumbens (NAc) associated with chronic antipsychotic-induced EPS. Male C57Bl/6J mice received daily injections of Olanzapine (Olz, 15 mg/kg), Clozapine (Clz, 20 mg/kg), or Haloperidol (Hal, 1 mg/kg), for a period of 11 weeks with a 4-day withdrawal period before the last dosage. Catalepsy for detection of EPS, along with open-field and rotarod tests, were assessed as behavioral correlates of motor responses. Additionally, FosB and phosphorylated-DARPP-32 immunohistochemistry were examined in striatal regions after treatment. All antipsychotics produced catalepsy and reduced open-field exploration, such as impaired rota-rod performance after Olz and Hal. The washout period was critical for Clz-induced side effects reduction. Both Olz and Clz increased FosB in NAc Shell-region, and phosphoThr34-DARPP-32 in NAc. Only Clz reduced phosphoThr75-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr34-Darpp-32-ir in the NAc Core region. This study provides evidence that atypical antipsychotics such as Olz and Clz also give rise to EPS effects frequently associated with a cumulative dosage of typical neuroleptics such as Hal. Nevertheless, FosB/phosphoThr34-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition.
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Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to prevent nausea and vomiting in palliative care and to treat chemotherapy-induced nausea and vomiting. This study aimed to examine whether pre-operative olanzapine, as a prophylactic anti-emetic added to intra-operative dexamethasone, ondansetron and total intravenous anaesthesia, reduced the incidence of postoperative nausea or vomiting. We performed a multiply-blinded randomised controlled trial in patients aged 18-60 years with cancer at high risk of postoperative nausea or vomiting (three or four risk factors according to the Apfel criteria) plus a previous history of chemotherapy-induced nausea and vomiting. Patients were allocated at random to receive 10 mg olanzapine or placebo orally 1 h before surgery in addition to a two-drug regimen (dexamethasone and ondansetron) and propofol anaesthesia to prevent postoperative nausea or vomiting. The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; 47 in the olanzapine group and 49 in the control group completed the study. The baseline characteristics of the groups were similar. The incidence of postoperative nausea or vomiting in the first 24 h after surgery was lower in the olanzapine group (12/47, 26%) than in the control group (31/49, 63%) (p = 0.008, RR 0.40 (95%CI 0.21-0.79)). Adding pre-operative oral olanzapine to intra-operative dexamethasone and ondansetron was highly effective in reducing the risk of postoperative nausea or vomiting in the first 24 hours after surgery in patients with a previous history of chemotherapy-induced nausea and vomiting and at least three Apfel risk factors for postoperative nausea or vomiting.
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Antieméticos , Antineoplásicos , Humanos , Antieméticos/uso terapéutico , Náusea y Vómito Posoperatorios/inducido químicamente , Olanzapina/efectos adversos , Ondansetrón/efectos adversos , Dexametasona , Método Doble CiegoRESUMEN
The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.
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Antipsicóticos , Trastorno del Espectro Autista , Trastorno Autístico , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Ratas , Masculino , Animales , Humanos , Trastorno Autístico/inducido químicamente , Trastorno Autístico/tratamiento farmacológico , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Olanzapina/efectos adversos , Trastorno del Espectro Autista/inducido químicamente , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico , Neuronas , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Conducta Animal , Conducta SocialRESUMEN
BACKGROUND AND OBJECTIVES: Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second-generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases. METHODS: In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature-induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro-inflammatory cytokine TNF-α were made. RESULTS: Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature-induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF-α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis. CONCLUSION: The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.
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Antipsicóticos , Enfermedades Óseas Metabólicas , Clozapina , Periodontitis , Humanos , Adulto , Ratas , Masculino , Femenino , Animales , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Olanzapina/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Wistar , Periodontitis/complicaciones , Enfermedades Óseas Metabólicas/inducido químicamente , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Aumento de PesoRESUMEN
The antipsychotic drug, olanzapine, is prescribed for postpartum psychosis. Possible adverse effects on fertility of offspring are unclear. We investigated the effects of administering olanzapine via lactation on testicular development and endocrine function of prepuberal male rats. Olanzapine was administered to mothers at 2.5, 5 or 10 mg/kg. We found in male offspring increased body weight, decreased gonadosomatic index, testicular weight and epididymal weight. The volume of seminiferous tubules, seminiferous epithelium, Leydig cells, intertubule tissue and lymphatic space was reduced in rat pups exposed to olanzapine. Tubule diameter and length, seminiferous epithelium height, Leydig cell size and nuclear diameter also were reduced. Testosterone levels were reduced in the groups exposed to olanzapine, while prolactin levels were increased. We observed histopathology in testes of animals whose mothers had been treated with 2.5 mg/kg olanzapine; more severe pathology was observed in offspring whose mothers were administered higher doses. Administration of olanzapine to mothers during lactation produced testicular and endocrine pathology in prepuberal rats in a dose-dependent manner.
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Lactancia , Testículo , Ratas , Femenino , Animales , Masculino , Olanzapina/farmacología , Testosterona , Atrofia/patología , Tamaño de los ÓrganosRESUMEN
Objective: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. Methods: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. Results: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. Conclusion: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.
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Risperidone/olanzapine are antipsychotics used in Peru to control symptoms of psychosis. The objective was to review the available evidence on potential pharmacokinetic interactions mediated by CYP1A2 and CYP2D6 polymorphic genes between risperidone or olanzapine and selected drugs for the treatment of COVID-19. A bibliographic search was conducted in SciELO and PubMed/Medline. The selection criteria included all types of articles in English and Spanish languages. In this review, the CYP1A2/CYP2D6/CYP3A4 genes that encode their respective enzymes have been described. The olanzapine/risperidone association increases the risk of prolonging the QT interval; chloroquine/hydroxychloroquine decreases metabolism and increases plasma concentration of risperidone; ritonavir decreases metabolism and increases plasma levels of hydroxychloroquine and lopinavir with the risk of prolonging the QT interval of the cardiac cycle and with a tendency to progression towards Torsades de Pointes. Ritonavir increases metabolism and decreases plasma levels of olanzapine. A low incidence of adverse effect was found between risperidone/azithromycin and olanzapine with azithromycin and hydroxychloroquine. Regarding the association of genes: CYP1A2*1D increases and CYP1A2*1F decreases the plasma concentration of olanzapine. Risperidone plasma levels are increased in CYP2D6 intermediate and poor metabolizers compared with normal metabolizers. Other studies indicate no significant association between poor metabolizers of CYP1A2 and CYP2D6 with increased pharmacokinetic parameters. It is concluded that there are potential risks of prolonging the QT interval due to pharmacokinetic interactions mediated by polymorphic genes CYP1A2 and CYP2D6 between risperidone or olanzapine and the drugs selected for the treatment of COVID-19.
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OBJECTIVE: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. METHODS: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. RESULTS: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. CONCLUSION: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Emociones , Litio/farmacología , Teorema de Bayes , Reproducibilidad de los Resultados , Expresión Facial , Imagen por Resonancia MagnéticaRESUMEN
Introdução: a olanzapina é um dos fármacos antipsicóticos benzodiazepínicos mais usados no mundo. Apesar da sua eficiência, em concentrações excessivas, ela sói ser tóxica, como quaisquer outros fármacos desta classe. Assim, neste trabalho, se avaliou, pela primeira vez, a possibilidade da detecção eletroquímica do fármaco olanzapina, assistida pelo compósito do oxihidróxido de cobalto (III), emparelhado com o dióxido, com um corante esquaraínico. Método: o modelo matemático trivariante correspondente inclui dois cenários de oxidação do fármaco, possíveis para o caso, incluindo a eletropolimerização indireta da molécula da benzodiazepina condensada, bem como a oxidação do fármaco pelo átomo do enxofre. Este modelo tem sido desenvolvido e analisado mediante a teoria de estabilidade linear e análise de bifurcações. Resultados e discussão: a análise do modelo há mostrado que a hibridez do mecanismo do processo eletroanalítico, aliada à composição e descomposição dos compostos iônicos aquando da sua realização, aumenta a probabilidade da ocorrência do comportamento oscilatório, em relação ao caso mais simples e mais comum. No entretanto, a instabilidade oscilatória se realiza nos valores dos parâmetros, que estão além do limite de detecção. Por sua vez, o estado estacionário se obtém e se mantém facilmente, indicando um processo eletroanalítico eficiente, controlado pela difusão do analito. Conclusões: trata-se de um processo eletroanalítico eficiente, em que o composto de cobalto funciona como substância ativa, e o corante desempenha o papel de mediador
SUMMARY Introduction: olanzapine is one of the most used antipsychotic drugs in the world. Although it is efficient, it may be toxic in excess. Therefore, in this work the possibility of olanzapine electrochemical determination over an electrode, modified by the cobalt (III) oxyhydroxide in pair with its dioxide in a composite with squaraine dye. Methods: the trivariant correspondent mathematical model includes two scenarios of the drug oxidation, possible for the case, including the indirect electropolymerization of the condensed benzodiazepine molecule, like also its oxidation by sulfur atom. This model has been developed and analyzed by means of stability theory and bifurcation analysis. Results and discussion: the analysis of the model has shown that the mechanism hybridity of the electroanalytical process, alongside with the formation and decomposition of ionic compounds during its realization, augments the possibility for the oscillatory behavior realization, relatively to the simplest and commonest case. Nevertheless, the oscillatory instability is realized in parameter values far beyond the detection limit. On the other hand, the stable steady-state is easy to obtain and maintain, indicating an efficient electroanalytical process, controlled by the analyte diffusion. Conclusions: the electroanalytical process is efficient. The cobalt compound is acting as an active substance, and the dye is the mediator.
Introducción: la olanzapina es uno de los fármacos antipsicóticos más utilizados en el mundo. Aunque es eficaz, puede resultar tóxico en exceso. Por tanto, en este trabajo se plantea la posibilidad de la determinación electroquímica de olanzapina sobre un electrodo, modificado por el oxihidróxido de cobalto (III) en pareja con su dióxido en un composito con colorante de escuaraína. Métodos: el modelo matemático correspondiente incluye dos escenarios de oxidación del fármaco, posibles para el caso, que incluyen la electropolimerización indirecta de la molécula de benzodiazepina condensada, así como su oxidación por átomo de azufre. Este modelo ha sido desarrollado y analizado mediante teoría de estabilidad y análisis de bifurcación. Resultados y discusión: el análisis del modelo ha demostrado que el mecanismo de hibridación del proceso electroanalítico, junto con la formación y descomposición de compuestos iónicos durante su realización, aumenta la posibilidad de realización del comportamiento oscilatorio, relativamente al caso más simple y común. Sin embargo, la inestabilidad oscilatoria se realiza en valores de parámetros mucho más allá del límite de detección. Por otro lado, el estado estacionario estable es fácil de obtener y mantener, lo que indica un proceso electroanalítico eficiente, controlado por la difusión del analito. Conclusiones: el proceso electroanalítico es eficiente. El compuesto de cobalto actúa como sustancia activa y el colorante es el mediador.
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Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits.Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real-world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up.Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex, and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyses were performed.Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference.Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyses.
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Antipsicóticos/uso terapéutico , Olanzapina/uso terapéutico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Brasil , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. METHODS: Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. RESULTS: Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p < .0001) for improving TTM symptoms. Clomipramine (SMD [95% CI] = -0.71 [-1.38, -0.05], p = .036), N-acetylcysteine (SMD [95% CI] = -0.75 [-1.36, -0.13], p = .017) and olanzapine (SMD [95% CI] = -0.94 [-1.77, -0.12], p = .025) demonstrated significant benefits compared to placebo in RCTs. CONCLUSIONS: BT-HRT has demonstrated the largest treatment effects and has the strongest evidence base for reducing TTM symptoms. In contrast, several pharmacological agents have demonstrated efficacy in single randomized clinical trials that would benefit from replication. Additional trials are needed to identify other effective medications for TTM and determine the relative efficacy of available agents.
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Tricotilomanía , Acetilcisteína , Terapia Conductista , Clomipramina/uso terapéutico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tricotilomanía/tratamiento farmacológicoRESUMEN
Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.
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Antipsicóticos/uso terapéutico , Lipidómica/métodos , Esquizofrenia/sangre , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Lipidómica/tendencias , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
Resumen Se han descrito una serie de reacciones adversas asociadas a antipsicóticos, entre las que destacan las reacciones adversas hematológicas propias de algunos antipsicóticos atípicos. Las más renombradas han sido clásicamente las discrasias sanguíneas asociadas al uso de olanzapina. En este trabajo nos enfocamos en una reacción adversa poco común: eosinofilia en un paciente esquizofrénico paranoide usuario de olanzapina, situación documentada en contadas publicaciones a lo largo de la historia de uso de este medicamento. Se trata de una reacción adversa infrecuente, y por lo mismo poco conocida y estudiada.
Many adverse effects of antipsychotic drugs have been described, among which hematologic adverse effects stand out. Classically, blood discrasias have been associated to the use of olanzapine. On this paper we will focus on an uncommon adverse reaction: eosinophilia in a patient diagnosed with a paranoid schitzophrenia, who had been using olanzapine. There have been just a few reported cases of eosinophilia secondary to the use of olanzapine, which makes this an infrequent, rarely known and even less studied adverse reaction.
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Humanos , Masculino , Adulto , Esquizofrenia , Antipsicóticos , Eosinofilia , OlanzapinaRESUMEN
OBJECTIVE: The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug. METHOD: A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups. RESULTS: During the study, 1.1% (n = 43) of the patients used clozapine at any time. Those on clozapine had significantly fewer manic and depressive symptoms during follow-up as compared with those on neither clozapine nor olanzapine, while those on olanzapine had more symptoms. The use of clozapine was not associated with an increased risk of hospitalization. No deaths were recorded for clozapine group during the trial. CONCLUSIONS: Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.
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Antipsicóticos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Clozapina/farmacología , Olanzapina/farmacología , Evaluación de Resultado en la Atención de Salud , Adulto , Antipsicóticos/administración & dosificación , Clozapina/administración & dosificación , Femenino , Hospitalización , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Olanzapina/administración & dosificación , Pacientes Ambulatorios , Desarrollo de Programa , Estados UnidosRESUMEN
Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Glucemia/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Aripiprazol/efectos adversos , Olanzapina/efectos adversos , Esquizofrenia/tratamiento farmacológico , Triglicéridos/sangre , Aumento de Peso/efectos de los fármacos , Índice de Masa Corporal , Factores Sexuales , Estudios Prospectivos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangreRESUMEN
Olanzapine (OLZ), a drug for the treatment of schizophrenia, presents in more than 60 crystal forms. Polymorphs I, II and III were reported, however, the preparation conditions for pure II and III have not been reported. Polymorph IV was reported but this form is actually polymorph II described at different temperature. The diversity of solid forms of OLZ, the change in the nomenclature found in the literature and the presence of polymorphic mixture in samples, increase the difficulty for a correct solid state characterization. Therefore, the goal was the polymorphic identification of three OLZ raw materials, highlighting the limitation of conventional techniques (typically used in analytical control) and the necessity to use a combination of advanced ones to solve this challenge. The samples were studied by conventional techniques such as powder X-ray diffraction, thermoanalytical techniques, infrared spectroscopy. In apart from that, synchrotron powder X-ray diffraction (SPXRD) and solid state nuclear magnetic resonance (ss-NMR) were used. All samples were in accordance with the pharmacopoeia criteria. However, the conventional techniques were not specific for the complete polymorphic identification. Therefore, a combination of advanced techniques (SPXRD and ss-NMR) was necessary to identify the mixture of polymorphs (I, II and III) in all samples.
Asunto(s)
Antipsicóticos/química , Espectroscopía de Resonancia Magnética/métodos , Olanzapina/química , Difracción de Rayos X/métodos , Cristalización , Espectrofotometría Infrarroja , Sincrotrones , Tecnología Farmacéutica/métodosRESUMEN
Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Antipsicóticos/análisis , Antipsicóticos/efectos adversos , Glucosa/efectos adversos , Insulina/efectos adversos , Páncreas/efectos de los fármacos , Análisis de Varianza , Risperidona/efectos adversos , Fumarato de Quetiapina/efectos adversos , Olanzapina/efectos adversosRESUMEN
Background Schizophrenia is a chronic mental disorder, characterized by positive, negative and cognitive symptoms. In general, several plants have shown activity in diseases related to the central nervous system (e.g., Erythrina velutina (EEEV), also known as "mulungu"). For this reason, we aimed to investigate the effects of standardized ethanol extract obtained from the stem bark of EEEV on the schizophrenia-like behaviors induced by ketamine (KET) administration. Methods Swiss mice were treated with KET (20 mg/kg, i.p.) or saline for 14 days. In addition, from 8th to 14th days, saline, EEEV (200 or 400 mg/kg, p.o.) or olanzapine (OLAN 2 mg/kg, p.o.) were associated to the protocol. On the 14th day of treatment, schizophrenia-like symptoms were evaluated by the prepulse inhibition of the startle reflex (PPI), locomotor activity evaluated by the open field test (OFT), spatial recognition memory evaluated by the Y-maze task and social interaction test (SIT). Results KET has caused deficits in PPI, and it has also has caused hyperlocomotion in OFT and deficits in SIT as compared to control. EEEV in both doses used, reversed behavioral changes induced by KET, likewise results obtained with the administration of OLAN. Conclusions Taken together, the results demonstrate that the standard extract of EEEV was able to revert schizophrenia-like symptoms, due to the administration in repeated doses of ketamine. Thus, our findings lead to a new perspective for the use of EEEV an interesting alternative for drug discovery in schizophrenia.