Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?

Intravascular papillary endothelial hyperplasia (Masson's tumor) is a reactive vascular lesion of obscure etiopathogenesis, often seen in the head and neck. Its presentation as a scalp swelling, however, is extremely uncommon. We describe the first report in an adult, being treated for bipolar illness. A young male presented with a right frontotemporal scalp swelling since 3 weeks. He was also being treated for bipolar illness with olanzapine. Examination revealed a soft, non-pulsatile swelling. After inconclusive aspiration results, a complete excision was performed. Histopathology revealed proliferating endothelial cells arranged as papillary fronds confined to vessel lumina, devoid of atypia, accompanied by thrombosed vessels facilitating a diagnosis of Masson's tumor. The patient is free of recurrence five months after surgery. Further studies on a possible effect of olanzapine on vascular proliferation in experimental in vivo and in vitro models would definitely aid in elucidating clinical relevance, if any.

Effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats / 中国药房

OBJECTIVE To investigate the effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats. METHODS SD rats were randomly divided into 4 groups according to single-dose administration and multiple-dose administration， with 6 rats in each group. Groups A and B were given olanzapine （5 mg/kg） or olanzapine （5 mg/kg）+Yiru tiaojing granules （0.972 g/kg） in a single gavage， and groups C and D were administered with the same method once a day for 14 d. Blood was collected from the orbital venous plexus before administration and 5， 15， 30 min and 1， 2， 3， 6， 8， 12， 24 h after the last administration， respectively. The blood concentration was determined by LC-MS， and the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS Compared with group A， group B showed a significant decrease in AUC0－24 h， AUC0－∞ and cmax （P＜0.05）， and a significant prolongation of MRT0－24 h， MRT0－∞ and CLz/F （P＜0.05）； there was no statistically significant difference in the pharmacokinetic parameters between group C and group D （P＞0.05）. CONCLUSIONS A single administration of Yiru tiaojing granules can inhibit the absorption of olanzapine in rats， and long-term administration of Yiru tiaojing granules does not have a significant effect on the pharmacokinetic process of olanzapine.

Nerve repair effect of olanzapine-mediated cyclic AMP response element binding protein/brain-derived neurotrophic factor/receptor tyrosine kinase receptors B pathway on schizophrenic rats / 解剖学报

Objective To stud)' the nerve repair effect of olanzapine on schizophrenia model rats through its effect on cyclic AMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase receptors B (TrkB) pathway. Methods Total 60 rats were divided into control group, model group, olanzapine low, middle and high dose group. The rats in the model group, olanzapine low, middle and high dose groups were injected intraperitoneally with MK-801[0. 2 mg/(kg-d) ], while the control injected with the same amount of normal saline. The low, middle and high dose olanzapine groups were perfused with olanzapine solution of 0. 5 mg/(kg-d),1. 0 mg/(kg-d) and 1. 5 mg/(kg-d) respectively. The behavior of rats was scored according to ataxia and stereotyped behavior standards, cognitive function and learning ability were evaluated by Moms water maze test, serum tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels were detected by ELISA method, hippocampal histopathology was observed under microscope, and apoptosis and expression of CREB/BDNF/TrkB pathway related proteins in hippocampus were detected. Results Compared with the control group, the ataxia, the score of stereotyped behavior, the expression of TNF-a, IL-6 and the rate of apoptosis in the model group increased significantly (P < 0 . 01). Compared with the control group, the number of crossing the platform, the time of staying in the target quadrant and the relative expression of CREB, p-CREB, p-TrkB, TrkB and BDNF protein in the model group decreased significantly (P<0. 01), and those in the low and middle dose olanzapine groups decreased significantly (P < 0 . 05). Compared with the model group, the times of crossing the platform and the stay time in the target quadrant increased significantly in the low and middle dose olanzapine groups (P< 0. 05). In the model group and the low dose olanzapine group, the hippocampal cells were swollen obviously, the nucleus was broken and divided, pyknosis, and the tissue aiTangement was disorderly, while the phenomenon of fragmentation and nuclear pyknosis was rarely seen in the middle and high dose olanzapine groups. Conclusion The nerve repair mechanism of olanzapine on schizophrenic model rats is related to improving cognitive impainnent, protecting hippocampal neurons and activating the expression of CREB/BDNF/TrkB signal pathway in rats.

Facial processing in bipolar disorder is mediated by clinical and biological aspects

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.

Homocysteine Levels and Clinical Outcomes in Schizophrenia—A Pilot Randomized Controlled Trial

Objectives: To find out the relation between homocysteine levels in peripheral blood and the effectiveness as well as the safety of haloperidol and olanzapine in schizophrenia treatment. Materials and Methods: A prospective randomized parallel-group open-label interventional clinical trial was conducted on 40 mild to moderate schizophrenia patients. To compare the efficacy of olanzapine and haloperidol Brief Psychiatric Rating Scale (BPRS) score was used. Homocysteine levels of peripheral blood and Abnormal Involuntary Movement Scale scores were evaluated. Results: BPRS score improved in both groups on day 14 and day 28. But significantly more with olanzapine (P value =.001). The olanzapine group showed a higher reduction (13.91±0.47 to 9.74±0.5) in homocysteine levels than the haloperidol group. Also, the BPRS scores negatively correlated (r = –0.66) to homocysteine levels. Conclusion: Therefore, our study shows that peripheral blood homocysteine levels can be used to predict and assess the treatment outcome in schizophrenia patients. Biomarker driven approach in schizophrenia will allow the patients to be treated promptly with the right drug. In this light, personalized treatment holds great potential in the future.

A case report of Olanzapine induced DRESS Syndrome

DRESS syndrome (Drug reaction with eosinophilia and systemic symptoms) is defined as a drug-induced complex of symptoms consisting of fever, rash, lymphadenopathy, eosinophilia and a wide range of mild to severe systemic presentations. Here we report a case of a 24-year-old female who developed a severe generalized Anasarca, skin erythema, facial puffiness, reddish discoloration over the body, fever, eosinophilia, leukocytosis and hepatitis 30 days after ingestion of olanzapine. Considering the occurrence of fever, eosinophilia, enlarged lymph nodes, typical skin rash and internal organ involvement, a ‘’ Probable diagnosis “of DRESS syndrome was made using the RegiSCAR Criteria. DRESS induced by psychotropic medications have been scarcely reported. Extensive reporting and educating clinicians as well as patients regarding DRESS will lead to decreased morbidity as well as mortality. Further research is warranted in elucidating its pathogenesis with the aim of designing personalized treatment plans

Therapeutic effects of risperidone combined with olanzapine on first-episode schizophrenia in 30 patients / 中国基层医药

Objective:To investigate the clinical efficacy of risperidone combined with olanzapine in the treatment of first-episode schizophrenia and its effects on serum homocysteine level and cognitive function.Methods:Sixty patients with first-episode schizophrenia who received treatment in Yiwu Mental Health Center from May 2017 to May 2018 were included in this study. They were randomly assigned to receive either olanzapine (control group, n = 30) or olanzapine and risperidone (observation group, n = 30) treatment. All patients received 4 weeks of treatment. We compared serum homocysteine level, cognitive function, and clinical efficacy between the two groups. Results:There was no significant difference in serum homocysteine level pre-treatment between the two groups ( P > 0.05). Serum homocysteine level post-treatment was significantly lower in the observation group than in the control group [(13.59 ± 2.61) mmol/L vs. (15.83 ± 2.58) mmol/L, t = 3.34, P < 0.05). There were no significant differences in the scores of each cognitive function item pre-treatment between the two groups (all P > 0.05). The scores of each cognitive function item post-treatment in the observation group was (15.06 ± 2.28) points, (21.18 ± 3.26) points, (44.39 ± 4.42) points, (40.63 ± 6.27) points, which were significantly superior to those in the control group [(13.31 ± 2.04) points, (19.26 ± 3.07) points, (42.43 ± 2.07) points, (44.19 ± 5.86) points, t = 3.13, 2.34, 2.12, 2.27, all P < 0.05]. The total improvement rate was significantly higher in the observation group than in the control group [93.33% (28/30) vs. 70.00% (21/30), χ2 = 5.45, P < 0.05). Conclusion:Risperidone combined with olanzapine is highly effective on first-episode schizophrenia. The combined therapy can reduce serum homocysteine level and improve cognitive function.

Based on PI3K/Akt signaling pathway to explore the effects of olanzapine on cognitive function and neuronal damage in schizophrenic rats / 解剖学报

Objective To explore olanzapine effect on the cognitive function and neuronal damage of aged schizophrenic rats based on the PI3 K/Akt signaling pathway. Methods Ten-week-old SD rats were randomly divided into a blank control group（n=12） and a modeling intervention group（n=48）. The modeling group were injected with didroxapine maleate [MK-801,0.2 mg/（kg·d）] for 14 days. And the model was evaluated by general behavioral studies to determine the success of model building. The model rats were randomly divided into model group and low, medium, and high dose olanzapine groups [10, 20, 40 mg/（kg·d）], each with 12 rats. The control group and model group were given distilled water; the low, medium, and high dose olanzapine groups were given olanzapine for 21 days. The stereotyped lines were scored by the standard of Sams Dodd and Hoffman, the cognitive evaluation of the rats was performed by the Morris water maze, and the levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in the serum were determined by ELISA. The activities of dihydrokaempferol（Ach） and acetyl cholinesterase（AchE）in brain tissue were detected by acetylcholinesterase activity assay kit. Rat brain tissue PI3 K, Akt, mammalian target of rapamycin（mTOR） mRNA expression levels were detected by Real-time PCR. Results Compared with the model group, the stereotyped behavior and ataxia scores, escape latency, number of crossing platforms, serum levels of IL-6, TNF-α, AchE, phosphorylated PI3 K（p-PI3 K）, phosphorylated Akt（p-Akt） protein expression decreased（P＜0.05 or P＜0.01）, while brain tissue Ach, PI3 K, mTOR and phosphorylated mTOR（p-mTOR） protein content increased（P＜0.05 or P＜0.01） in the low, medium and high dose olanzapine groups. The content of Akt was increased in the low-dose group. Compared with the model group, Akt and mTOR mRNA in the brain tissue of rats in the low, medium, and high-dose alanzapine groups expression levels were down-regulated（P＜0.05 or P＜0.01）. PI3 K mRNA in the brain tissue of rats in the low, medium, and high-dose alanzapine groups expression levels were down-regulated（P＜0.05 or P＜0.01）. Conclusion Olanzapine can reduce stereotyped behavior and ataxia scores, escape latency, number of crossing platforms, IL-6, TNF-α, AchE and increase Ach content and regulate the PI3 K/Akt signaling pathway to relieve the schizophrenia.

Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5 / 中南大学学报(医学版)

OBJECTIVES@#Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD.@*METHODS@#This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively.@*RESULTS@#After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced.@*CONCLUSIONS@#The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.

A descrição teórica da detecção eletroquímica do fármaco olanzapina, assistida pelo compósito do oxihidróxido de cobalto (III) com um corante esquaraínico

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.

Is a Glucocorticoid Antagonist a Potential Treatment Alternative for Antipsychotic-Induced Weight Gain?

Objective: To evaluate the efficacy and safety of mifepristone as a new treatment modality for antipsychotic-induced weight gain. Methods: We searched databases up to March 2021, for the published English-language literature including a Medical Subject Heading “Mifepristone,”“Receptors, Glucocorticoid,” “Weight gain,” “Overweight,” “Obesity,” “Body Weight Change,” “Antipsychotics Agents,” “Glucocorticoid Receptor Blocker,” “Glucocorticoid Receptor antagonist.” We identified two clinical and four preclinical studies utilizing mifepristone as a treatment modality. Results: The results of the olanzapine clinical trial showed that mean increase in weight from baseline to day 14 was greater in the olanzapine with the placebo group (3.2 ± 0.9 kg) than the olanzapine with mifepristone group (2.0 ± 1.2 kg) and the mifepristone with placebo (2.0 ± 0.7 kg), and a similar effect was observed in the risperidone with mifepristone clinical trial. Conclusions: Mifepristone shows potential in the management of AIWG. Glucocorticoid antagonists can be a viable alternative to curb this side effect. Large-scale clinical studies are warranted to determine the medication’s safety and efficacy based on this mechanism of action.

Treatment progress of weight gain and abnormal lipid metabolism in patients with schizophrenia caused by clozapine and olanzapine / 四川精神卫生

To address the issue of weight gain and abnormal lipid metabolism caused by clozapine and olanzapine administration in patients with schizophrenia， a qualitative and systematic review was carried out， thus providing references for clinical treatment and future research. This review embraces the aspects of pharmacotherapy， traditional Chinese medicine treatment and so on.

Olanzapine-induced hiccups： a case report / 四川精神卫生

The case report aims to raise the concern of clinicians about hiccups as an adverse reaction in olanzapine treatment. A 47-year-old male patient with epileptic mental disorder appeared symptoms of persistent hiccups on the fourth day of treatment with sodium valproate and carbamazepine jointing 10 mg/d olanzapine， and the symptoms disappeared two days after olanzapine withdrawal. The patient began to take olanzapine again， hiccups reappeared seven days after administration and relieved two days after withdrawal. During the whole treatment period， the dosage of sodium valproate and carbamazepine remained unchanged， indicating that the hiccups was induced by olanzapine. This case suggests that the possibility of hiccups should be considered in the clinical application of olanzapine.

Efficacy of sertraline combined with low-dose olanzapine in patients with depression and anxiety comorbidity / 四川精神卫生

ObjectiveTo observe the efficacy and safety of sertraline combined with low-dose olanzapine in the treatment of depression and anxiety comorbidity and its effect on sleep quality， so as to provide references for the related clinical treatment. MethodsA total of 121 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for depressive episode and generalized anxiety disorder in The Third People's Hospital of Tianshui and the Sanatorium for Mental Illness of Veterans in Tianshui from October 2019 to August 2020 were enrolled， and they were divided into two groups according to the random number table method. Study group （n=61） received sertraline combined with low-dose olanzapine， while control group （n=60） received sertraline only. Then the disease severity degree， sleep quality and adverse reactions were assessed using Hamilton Depression Scale - 17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， Pittsburgh Sleep Quality Index （PSQI） and Treatment Emergent Symptom Scale （TESS） at the baseline， 1st， 2nd， 4th， 6th and 8th weekend， respectively. ResultsPost-treatment HAMD-17， HAMA and PSQI scores in both groups were lower than those before treatment （P<0.05）. At each time point after treatment， HAMD-17， HAMA and PSQI scores of study group were lower than those of control group， with statistical significance （P<0.05）. ConclusionSertraline alone and its combination with low-dose olanzapine are both effective in the treatment of depression and anxiety comorbidity， while the combination therapy achieves better efficacy and higher safety in alleviating anxiety and insomnia symptoms.

Gabapentin treatment in olanzapine-induced restless legs syndrome： a case report / 四川精神卫生

The purpose of this study is to suggest the physicians using olanzapine to strengthen the recognition and treatment of restless leg syndrome （RLS） in clinical practice. In this paper， one patient with schizophrenia suffered from RLS during olanzapine administration， which was characterized by unpleasant sensory disturbances in bilateral lower extremity at night， intense urges to move legs， and inability to sleep. After taking gabapentin， the above symptoms were significantly improved.

Efficacy and safety of the combination of agomelatine and low-dose olanzapine in 184 cases of postprandial distress syndrome with depression, anxiety and sleep disorders / 中华消化杂志

Objective:To observe the efficacy and safety of the combination of agomelatine and low-dose olanzapine (AO) in the treatment of postprandial distress syndrome (PDS) with depression, anxiety and sleep disorders.Methods:From April 2019 to September 2020, PDS patients with depression, anxiety and sleep disorders in Tianjin Medical University General Hospital were selected and divided into AO group and flupentixol-melitracen (FM) group. Patients of the AO group were given oral agomelatine 25 mg and AO 1.70 mg (both once per day), and the patients of FM group were given oral FM 10.5 mg (once per day), and all patients took itopride 50 mg (three times per day) at the same time. The total treatment course was eight weeks. Nepean dyspepsia index-symptom (NDIS), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Pittsburgh sleep quality index (PSQI) were used to evaluate the gastrointestinal symptoms, depression, anxiety and sleep disorders before treatment and two, four and eight weeks after treatment, respectively. The efficacy was evaluated according to the changes of scores of gastrointestinal symptoms before and after treatment. The adverse effects after medication were recorded. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 184 PDS patients with depression, anxiety and sleep disorders were enrolled, including 98 patients in AO group and 86 patients in FM group. At two, four and eight weeks after treatment, NDIS, PHQ-9, GAD-7 and PSQI scores of AO group and FM group were all lower than those of each group before treatment (AO group: 13.73±0.53, 10.13±0.44 and 7.87±0.31 vs. 27.08±0.84; 6.04±0.35, 4.70±0.31 and 3.81±0.22 vs. 10.04±0.50; 6.36±0.30, 5.29±0.28 and 4.21±0.19 vs. 10.71±0.51; 6.64±0.37, 5.27±0.35 and 4.09±0.30 vs. 11.14±0.42; FM group: 15.33±0.58, 11.58±0.50 and 9.80±0.35 vs. 25.10±0.79; 6.79±0.35, 5.71±0.32 and 4.86±0.30 vs. 9.11±0.46; 7.27±0.31, 6.51±0.32 and 5.21±0.27 vs. 9.79±0.44; 8.01±0.33, 6.76±0.32 and 5.78±0.32 vs. 10.44±0.32), and the differences were statistically significant (AO group: tNDIS=13.470, 17.930 and 21.530, tPHQ-9=6.488, 8.991 and 11.300, tGAD-7=7.361, 9.315 and 11.031, tPSQI=7.088, 9.736 and 12.550. FM group: tNDIS=9.921, 14.400 and 17.640, tPHQ-9=4.032, 6.106 and 7.781, tGAD-7=4.638, 5.993 and 8.840, tPSQI=5.289, 8.199 and 10.310, all P<0.05). At two, four and eight weeks after treatment, NDIS, GAD-7 and PSQI scores of AO group were all lower than those of the FM group during the same period (NDIS: 13.73±0.53 vs. 15.33±0.58, 10.13±0.44 vs. 11.58±0.50, 7.87±0.31 vs. 9.80±0.35; GAD-7: 6.36±0.30 vs. 7.27±0.31, 5.29±0.28 vs. 6.51±0.32, 4.21±0.19 vs. 5.21±0.27; PSQI: 6.64±0.37 vs. 8.01±0.33, 5.27±0.35 vs. 6.76±0.32, 4.09±0.30 vs. 5.78±0.32), and the differences were statistically significant ( tNDIS=2.018, 2.225 and 4.156, tGAD-7=2.097, 2.869 and 2.536, tPSQI=1.951, 2.359 and 3.099, all P<0.05). At eight weeks after treatment, the total effective rate of the AO group was higher than that of the FM group (94.9%, 93/98 vs. 84.9%, 73/86), and the difference was statistically significant ( χ2=5.205, P=0.026). The incidence of adverse reactions of constipation and somnolence of the AO group were both lower than those of the FM group (2.0%, 2/98 vs. 9.3%, 8/86 and 1.0%, 1/98 vs. 8.1%, 7/86, respectively), and the differences were statistically significant ( χ2=4.699 and 5.582, P=0.047 and 0.027). Conclusion:AO may be a treatment option for PDS with depression, anxiety and sleep disorders.

Effects of olanzapine versus risperidone on cognitive function and serum complement and high-sensitivity C-reactive protein levels in patients with schizophrenia / 中国基层医药

Objective:To investigate the effects of olanzapine versus risperidone on cognitive function, serum complement C3 and C4 levels and high sensitivity C-reactive protein (hs-CRP) level in patients with schizophrenia. Methods:Eighty patients with schizophrenia who received treatment in Lishui Second People's Hospital, China between September 2018 and September 2019 were included in this study. They were randomly assigned to receive treatment either with olanzapine (olanzapine group, n = 40) or risperidone (risperidone group, n = 40). Before and after treatment, the Positive and Negative Syndrome Scale (PANSS) score and the Wisconsin Card Sorting Test score were evaluated in each group. Before and after treatment, serum levels of dopamine, serotonin, norepinephrine, complement C3 and C4 and hs-CRP levels were compared between the olanzapine and risperidone groups. Results:Before treatment, there were no significant differences in PANSS and WCST scores between the two groups (both P > 0.05). After treatment, PANSS score, the number of perseverative errors and the number of random errors in each group were significantly decreased compared with before treatment [olanzapine group: (56.23 ± 9.37) points, (13.06 ± 6.26) points, (16.23 ± 6.35) points, t = 12.334, 5.885, 3.840, all P < 0.05; risperidone group: (55.98 ± 10.21) points, (13.97 ± 6.54) points, (16.31 ± 6.32) points, t = 12.044, 6.213, 3.321, all P < 0.05]. After treatment, the number of correct sorts and the number of categories in each group were significantly increased compared with before treatment [olanzapine group: (29.21 ± 2.24) points, (3.79 ± 1.12) points, t = 3.323, 2.087, both P < 0.05; risperidone group: (29.33 ± 2.35) points, (3.81 ± 1.15) points, t =2.750, 2.085, both P < 0.05]. After treatment, there were significant differences in these indexes between the two groups (all P > 0.05). Before treatment, there were no significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups (all P > 0.05). After treatment, serum levels of dopamine, serotonin and norepinephrine in each group were significantly decreased compared with before treatment [olanzapine group: (5.02 ± 0.13) μg/L, (66.24 ± 6.05) μg/L, (27.32 ± 4.05) μg/L, t = 67.800, 9.977, 5.082, all P < 0.05; risperidone group: (4.18 ± 0.12) μg/L, (63.12 ± 6.21) μg/L, (24.81 ± 4.13) μg/L, t = 99.761, 12.296, 6.882, all P < 0.05]. After treatment, there were significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups ( t = 30.029, 2.276, 6.882, all P < 0.05). Before treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups (all P > 0.05). After treatment, complement C3 and C4 and hs-CRP levels in each group were significantly increased compared with before treatment [olanzapine group: (1.12 ± 0.18) g/L, (0.24 ± 0.06) g/L, (1.09 ± 0.11) mg/L, t = 5.129, 4.049, 32.452, all P < 0.05; risperidone group: (1.13 ± 0.17) g/L, (0.25 ± 0.07) g/L, (1.10 ± 0.12) mg/L, t = 5.147, 5.164, 29.227, all P < 0.05]. After treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups ( t = 0.255, 0.686, 0.389, all P > 0.05). Conclusion:Olanzapine and risperidone have the same effects on improving the mental symptoms and cognitive function of patients with schizophrenia, but risperidone has more obvious effects on improving the body function than olanzapine.

Eosinofilia inducida por Olanzapina: A propósito de un caso / Olanzapine-induced eosinophilia: A case report

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.

Drug utilization study in schizophrenia patients in outpatient department of psychiatry: an observational prospective study

Background: A mental disorder or psychiatry disorder is a behavioural or mental pattern that causes significant distress or impairment of personal functioning. Schizophrenia is one of the most common psychiatric disorders. Aim of the study is to study drug utilization pattern in schizophrenia patients in outpatient department of psychiatry.Methods: A prospective and observational study was conducted in psychiatry outpatient department between May 2018 to October 2018 at Government Medical College and Hospital Aurangabad. Approval from ethics committee was taken. Data collected was of age, sex, final diagnosis, drugs prescribed to patients from case report form. The data obtained was then analyzed in Microsoft excel.Results: Total prescriptions of 129 patients were analyzed. Out of 129 patients 99 (76.74%) were male, while 30 (23.26%) were female. The mean age of the patients admitted in Psychiatry OPD was 36.71±11.76 years. Number of drugs prescribed per patient being 3.40±1.12 (mean±SD). The most common drugs used were olanzapine (66.6%), trihexyphenidyl (51.9%), lorazepam (44.9%), risperidone (39.5%), trifluoperazine (27.9%).Conclusions: Our study shows that atypical antipsychotics were the most common drugs prescribed in patients. Olanzapine was the most common medication used followed by risperidone. Our prospective study is carried out to get a more comprehensive data so that we can improve the drug utilization in our hospital.

Determination of Lamotrigine, Olanzapine and Quetiapine in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Therapeutic Drug Monitoring / 中国药学杂志

OBJECTIVE: To establish a highly sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of the concentrations of lamotrigine, olanzapine and quetiapine in human plasma to provide guidance for clinical drug use. METHODS: The plasma samples were precipitated by methanol, voriconazole was used as internal standard, and then gradiently eluted by ACQUITY UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) using mobile phase consisting of 0.1% formic acid solution and methanol. Multiple reaction monitoring (MRM) was conducted in ion detection mode using positive electrospray ionization source. RESULTS: The linear ranges of the calibration curves for lamotrigine, olanzapine and quetiapine in human plasma were 0.5-20 μg•mL-1, 2-200 and 10-1 000 ng•mL-1, respectively. The method had good matrix effect, extraction recovery, accuracy, precision and stability, and was successfully applied to analyze plasma samples of 45 patients. CONCLUSION: The UPLC-MS/MS method for determination of lamotrigine, olanzapine and quetiapine is proven to be a sensitive and reliable protocol for clinical therapeutic drug monitoring.