Olanzapine Therapy Research Articles

An economic model to understand the cost-effectiveness of olanzapine orally dispersible tablets (ODT) and olanzapine film coated tablets as a group compared with other oral atypical antipsychotics for treating schizophrenia in Morocco

BackgroundAntipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco.MethodsThe study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty.ResultsAccording to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings.ConclusionsThe model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations.

Olanzapine-induced multifactorial chylomicronaemia syndrome: a rare but important complication.

We present a case of a 42-year-old man who developed acute onset severe hypertriglyceridaemia within days of commencing olanzapine therapy. Despite having a family history of metabolic syndrome, he had no personal history of hyperlipidaemia and had normal fasting lipids 1 week prior to treatment initiation. His case is consistent with a diagnosis of multifactorial chylomicronaemia syndrome with a possible undiagnosed underlying genetic lipid metabolism disorder. Our case highlights the difficulty in identifying patients at risk of severe hypertriglyceridaemia prior to the commencement of olanzapine. Atypical antipsychotic medications, in particular olanzapine and clozapine, are associated with metabolic side effects. Olanzapine can precipitate acute onset severe hypertriglyceridaemia consistent with multifactorial chylomicronaemia syndrome. It is difficult to predict individuals at risk of olanzapine-induced hypertriglyceridaemia. This case demonstrates the importance of metabolic screening prior to the commencement of olanzapine and the possibility of repeating fasting serum lipids soon thereafter.

In vivo Characterization of the Opioid Receptor-Binding Profiles of Samidorphan and Naltrexone in Rats: Comparisons at Clinically Relevant Concentrations.

The atypical antipsychotic olanzapine is approved for the treatment of schizophrenia and bipolar I disorder; however, weight gain and metabolic dysregulation associated with olanzapine therapy have limited its clinical utility. In clinical studies, treatment with the combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain while providing antipsychotic efficacy similar to that of olanzapine. Although samidorphan is structurally similar to the opioid receptor antagonist naltrexone, the two differ in their pharmacokinetics and in vitro binding affinities to mu, delta, and kappa opioid receptors (MOR, DOR, and KOR, respectively). The objective of this series of nonclinical studies was to compare the in vivo binding profiles of samidorphan and naltrexone and their receptor occupancies at MOR, DOR, and KOR in rat brains. Male rats were injected with samidorphan or naltrexone to obtain total and unbound plasma and brain concentrations representing levels observed in humans at clinically relevant oral doses. Subsequently, samidorphan and naltrexone brain receptor occupancy at MOR, DOR, and KOR was measured using ultra-performance liquid chromatography and high-resolution accurate-mass mass spectrometry. A dose-dependent increase in samidorphan occupancy was observed at MOR, DOR, and KOR (EC50: 5.1, 54.7, and 42.9 nM, respectively). Occupancy of naltrexone at MOR (EC50: 15.5 nM) and KOR was dose dependent; minimal DOR occupancy was detected. At the clinically relevant unbound brain concentration of 23.1nM, samidorphan bound to MOR, DOR, and KOR with 93.2%, 36.1%, and 41.9% occupancy, respectively. At 33.5 nM, naltrexone bound to MOR and KOR with 79.4% and 9.4% occupancy, respectively, with no binding at DOR. At clinically relevant concentrations, samidorphan occupied MOR, DOR, and KOR, whereas naltrexone occupied only MOR and KOR. The binding profile of samidorphan differs from that of naltrexone, with potential clinical implications.

Dopamine receptor DRD1 expression (mRNA, protein level) in peripheral blood lymphocytes and prognosis of antipsychotic therapy

Introduction. There is a problem in predicting the efficacy and safety of antipsychotic therapy. Dopamine receptor D1 is one of the targets of antipsychotics. Peripheral blood lymphocytes (PBL) are the research object of neurotransmission receptors.The objective was to study DRD1 gene expression (mRNA, protein level) in PBL as a possible biomarker of olanzapine and haloperidol therapy prognosis.Methods and Materials. Sample: 106 patients diagnosed with schizophrenic spectrum disorder. Study design: prospective longitudinal follow-up with drug administration by randomization. Assessment of mental status and development of Parkinsonism: Positive and Negative Syndrome Scale (PANSS) and Simpson-Agnus Scale (SAS), respectively. PBL was study material. DRD1 mRNA level was determined by real-time PCR. DRD1 protein concentration in PBL was measured by enzyme immunoassay.Results. Haloperidol (but not olanzapine) treatment for 28 days, leads to DRD1 protein concentration decrease in PBL in a manner dependent on its initial level. DRD1 mRNA level in PBL remained unchanged during the treatment. Patients with effective therapy by olanzapine had lower DRD1 mRNA levels. Side effects of the therapy (Parkinsonism, weight gain) were not associated with studied DRD1 parameters.Conclusions. Haloperidol treatment leads to a decrease of DRD1 protein concentration in PBL, which depends on the initial protein level. Effective olanzapine therapy is associated with reduced DRD1 mRNA level in PBL before the treatment.

Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients-the significant impact of gene polymorphisms.

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples (n=30 patients) were taken before treatment (T1), after 10±1days (T2), and after 3±1months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography-mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. GSTM1 gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.

Early Lipid Metabolic Effects of the Anti-Psychotic Drug Olanzapine on Weight Gain and the Associated Gene Expression.

BackgroundAtypical antipsychotics such as olanzapine often cause metabolic side effects such as obesity and diabetes, leading to an increased risk of nonalcoholic fatty liver disease. The aim of the present study was to investigate the effects of olanzapine treatment on hepatic lipid metabolism and its possible relationship with adipose tissue status.MethodsUsing a female rat model, we investigated the effects of chronic olanzapine administration on the regulation of carbohydrate and lipid metabolism including lipid biosynthesis, oxidation, efflux, and lipolysis in liver and adipose tissue.ResultsThe body weight, liver mass and visceral adiposity after olanzapine treatment (2 mg/kg) for five weeks were not significantly different compared with vehicle controls. The serum level of triglycerides was higher in the vehicle controls than in olanzapine-treated rats. Unexpectedly, olanzapine treatment did not reduce glucose tolerance in our model. The expression of functional thermogenic protein uncoupling protein 1 (UCP1) was increased in brown adipose tissue (BAT) of the olanzapine group. Additionally, olanzapine treatment also reduced adipose inflammation in white adipose tissue (WAT). The transcription factor sterol regulatory element-binding protein (SREBP)-1c, a key early regulator of lipogenesis, was downregulated following olanzapine treatment. The expression of genes related to the triglycerides synthesis apparatus in the liver was upregulated in the olanzapine group. Olanzapine treatment induced genes involved in PPAR-α signaling and mitochondrial fatty acid oxidation in response to increased ATGL-mediated lipolysis in the liver.ConclusionTogether, our findings suggest a complicated link between olanzapine therapy and metabolic disturbance and may garner interest in assessing the action of antipsychotic-induced metabolic disturbances.

Comparison of Efficacy and Safety between Standard Triple Antiemetic Therapy and Additional Olanzapine Therapy for Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Meta-analysis of Randomized Controlled Trials

Comparison of Efficacy and Safety between Standard Triple Antiemetic Therapy and Additional Olanzapine Therapy for Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Meta-analysis of Randomized Controlled Trials

Doświadczenia w stosowaniu olanzapiny w warunkach oddziału stacjonarnego – przypadki kliniczne

Treating both schizophrenia and bipolar disorder require chronic drug therapy that must be chosen after careful consideration of the gains and losses associated with it. Hence, the process of the drug selection must take into account both the profile of patient’s symptoms and his coexisting diseases as well as the patient’s tolerance of earlier therapies. Olanzapine reduces positive symptoms of psychosis and enables stabilization in terms of affective episodes via blocking dopaminergic receptors. An important problem related to olanzapine therapy is its negative effect on the metabolism of carbohydrates and lipids. For this reason, appropriate information for the patient and implementation of appropriate prophylaxis, including monitoring of metabolic parameters, are recommended. Despite the risk of metabolic complications in some patients, olanzapine remains at the forefront of antipsychotic drugs, due to the good balance of benefits and losses associated with pharmacotherapy. In this paper, we present two clinical cases of patients who have been treated with olanzapine for schizophrenia and bipolar disorder.

What to Do About Missed Doses? A Retrospective Study of Olanzapine in the Elderly.

BackgroundSchizophrenia is characterized by a high disease burden. Olanzapine is a common drug used in antipsychotic medication. Little is known about the population pharmacokinetics of olanzapine in elderly patients. Missed doses are a common and unavoidable issue during the treatment of psychiatric diseases, especially in elderly patients. This study aimed to identify what an elderly person should do if doses are inadvertently missed.MethodsData were collected from 140 elderly psychiatric patients (aged ≥65 years) who received olanzapine therapy. Olanzapine concentrations were determined by high pressure liquid chromatographic tandem mass spectrometry (HPLC-MS/MS) and a population-based approach was used to quantify the characteristics of elderly patients. A non-linear mixed-effects model was used for data analysis. Simulations based on the final model were applied to predict situations involving a single missed dose or three consecutive missed doses under several remedial regimens.ResultsA total of 474 samples from 140 elderly patients were included in the therapeutic drug monitoring (TDM) data analysis. A one-compartment model, with no significant covariates, was developed to describe the population pharmacokinetics of olanzapine in elderly patients. The population predicted systematic clearance (CL/F) and volumes of distribution (V/F) were 18 L/h and 785 L, respectively. The simulation demonstrated that in a missed dose situation, elderly patients should take the regular dose immediately; the refill dose used at the second remedial time point depends on the length of the time delay.ConclusionHere, we used a simulation to provide a remedial regimen for missed doses of olanzapine in the elderly population. Our simulation can provide valuable suggestions for individualized therapy in elderly patients.

Calcium Levels Differences in Men with Schizophrenia Treated with Olanzapine and Risperidone in Prof. Dr. M Ildrem Psychiatric Hospital Medan

BACKGROUND: Second generation of antipsychotic medications is widely administrated in Indonesia and there is a distinctive difference in plasma calcium level in those receiving risperidone and olanzapine. According to several studies, decreased bone density is one of the deleterious effects affecting schizophrenic individuals receiving risperidone and olanzapine. AIM: The objective of the study was to determine the difference in serum calcium levels between men with schizophrenia who treated with olanzapine and risperidone at Prof. Dr. M Ildrem Psychiatric Hospital, Medan. METHODS: This is an experimental pre-test and post-test that compares two groups, namely the intervention group and the control group. Eligible subjects are those who meet our inclusion criteria in the following; age between 15 and 35 years old, total score of PANSS between 90 and 150, and normal serum calcium level. The subjects of the study were 60 men with schizophrenia, namely 30 who received olanzapine and 30 who received risperidone. The sampling method is non-probability sampling with a consecutive sampling type. RESULTS: There was a decrease in the total serum calcium level with the antipsychotic risperidone and olanzapine after 4 weeks, and a higher decrease occurred in the risperidone treatment group compared to olanzapine (p = 0.023). CONCLUSION: There was a significant decrease in serum calcium levels among men with schizophrenia who received risperidone therapy compared with those who received olanzapine therapy between the beginning and the end of week 4. It is expected that clinicians can consider giving antipsychotic therapy olanzapine in people with schizophrenia with low calcium levels.

Rare and Underestimated Association of Pulmonary Embolism and Olanzapine Therapy; Report of Two Cases.

Venous thromboembolic disease (VTD) is a very common and severe pathological condition in which there are many predisposing factors. Olanzapine is a drug frequently used in psychiatric practises; it is thought to increase the risk of VTD. Here, we report two cases, a young man and a woman, with a medical history of schizophrenia treated by olanzapine who developed pulmonary embolism and we did not find any aetiologies of VTD in them. Due to the link between olanzapine and pulmonary embolism, which has been previously described, olanzapine is considered responsible for this problem. Two mechanisms have been reported in the literature in this regard; significant weight gain and lethargy, which are very common side effects of olanzapine. So far, no direct effect of olanzapine on platelet aggregation or coagulation has been found. In patients developing VTD while being treated with olanzapine, discontinuation of olanzapine as a treatment option must be done with an adjustment of antipsychotic treatment and regular monitoring of psychic symptoms. Since the diagnosis of pulmonary embolism is not easy to make in a schizophrenic patient, clinicians should take that in consideration when prescribing these drugs and when facing clinical situations where VTD is suspected.

Drug utilization evaluation of olanzapine and assessment of adverse drug reactions associated in psychotic patients in a Tertiary Care Hospital

Objectives: To review the drug utilization and evaluation pattern of olanzapine and assessment of adverse drug reaction associated in psychotic patients in a tertiary care hospital. Methodology: A prospective Observational study was conducted in Department of Psychiatry, MVJ Medical College and Research Hospital, Bangalore, South India. Study was conducted for 6 months in In-patients who are diagnosed as suffering from psychosis which includes schizophrenia, delusional disorders, schizo-affective disorders, acute and transient psychosis and BPAD as per ICD 10 criteria. The utilization pattern of olanzapine therapy were assessed using case record forms with overall demographic data information was collected and ADR is assessed using standard scales. Result: Among 108 patients enrolled into the study 68 patients were under olanzapine therapy and rest were under other antipsychotics. A total of 68 patients olanzapine therapy patients out of which 51%were females and 49% were males. Majority of the patients belong to the age group of 28-37years and 18–27 years and 66% patients were married. Schizophrenia was found to be the common type of psychotic disorders with 63%. Even among the various psychotic disorders there was a slight female predominance. The hospitalization period was 12.43±8.4days. Majority of the patients had normal body mass index. Out of 68 patients 16 patients had switch over from olanzapine to other second-generation antipsychotics. Conclusion: This study has assessed for prescribing pattern of olanzapine in psychotic patients using a specially modified case reporting form. Olanzapine is most commonly prescribed antipsychotic compared to other antipsychotics for the treatment of paranoid schizophrenia and also in certain cases of bipolar affective disorder with mania or mixed episodes. Maximum patients were having paranoid schizophrenia.

Antipsychotic Drug Induced Tardive Dyskinesia

A typical antipsychotics are at a lower risk of developing extra-pyramidal symptoms (EPS). But now, atypical antipsychotics are increasingly being associated with neurological side effects such as tardive dyskinesia, tardive dystonia, akinesia, parkinsonism, akathisia, bradykinesia, tremor etc. in which one of the major cases reported is Olanzapine induced tardive dyskinesia (TD). Schooler and Kane criteria is used for diagnosing tardive dyskinesia. Many cases have been published on this particular drug-induced side effect. In many instances tardive dyskinesia is misdiagnosed as tardive dystonia. Here we report the case of tardive dyskinesia associated with the use of antipsychotic drugs in a 50-year-old adult male suffering from persistent delusional disorder in a tertiary health care centre in India. The patient was on Olanzapine therapy for more than 2 years. Upon recurrent episodes of somatic delusions, Olanzapine dose was increased. When the patient developed symptoms of TD, the dose of Olanzapine was de-escalated. Even though the drug dose was reduced, the symptoms persisted which lead to the diagnosis of olanzapine induced TD. Based on this, Olanzapine was stopped and Clozapine treatment was initiated. On follow up, the patient was found to be relieved of the symptoms and complete recovery was achieved after 2 months of clozapine treatment.

Plasma olanzapine concentration: Relation with dose, adherence to medication, and clinical efficacy

Objective: To estimate plasma olanzapine concentration (POC) using liquid chromatography-mass spectrometry (LCMS) and identify factors that contributes to pharmacokinetic variability of olanzapine. Materials and Methods: This was a prospective, observational study initiated after approval of institutional ethics committee. Stable patients of schizophrenia on olanzapine, above 18 years of age, of either gender, on olanzapine therapy for at least 12 weeks with no change in dose for at least one week were included. Plasma levels of olanzapine were assessed using HPLC based kit on LCMS. To assess response to treatment patients were subjected to Brief Psychiatric Rating Scale (BPRS) in which lower score indicates better response. Adherence to therapy was assessed by using Morisky 8-Item Medication Adherence Questionnaire in which lower score indicates better adherence. Graph pad prism version 6.0 was used for statistical analysis. Results: POC was higher in women compared to men. No correlation was observed between POC and age (r = 0.01343, p= 0.9470) or daily dose of olanzapine(r= -0.2765, P = 0.1626). Patients having POC more than 20 ng/ml had better adherence (Morisky’s score 1 or 2) to medication compared to those having POC less than 20 ng/ml. Significant correlation was observed between POC and clinical response(r = -0.4371, p=0.0226). Conclusion: TDM of olanzapine is important considering large interpatient variability in POCs at the same dosages. It can also help in improving efficacy, particularly when patients do not respond to therapeutic doses or when they develop adverse effects. Cost of the procedure is a major concern which needs to be considered before this can be established in routine practice. Keywords: TDM, Antipsychotics, BPRS, LCMS, Schizophrenia.

Effects of olanzapine treatment on lipid profiles in patients with schizophrenia: a systematic review and meta-analysis

Olanzapine-induced dyslipidemia significantly increases the risk of cardiovascular disease in patients with schizophrenia. However, the clinical features of olanzapine-induced dyslipidemia remain hitherto unclear because of inconsistencies in the literature. This meta-analysis thus investigated the effects of olanzapine treatment on lipid profiles among patients with schizophrenia. Studies of the effects of olanzapine on lipids were obtained through the PubMed, Web of science, The Cochrane Library and Embase databases (up to January 1, 2020). Twenty-one studies and 1790 schizophrenia patients who received olanzapine therapy were included in our analysis. An olanzapine-induced increase was observed in plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels in patients with schizophrenia (all P < 0.05). Moreover, the time points analyzed included the following: baseline, 4 weeks, 6 weeks, 8 weeks, 12 weeks, and ≥ 24 weeks (data of ≥ 24 weeks were integrated). The significant elevation of TG, TC, and LDL-C was observed in patients with schizophrenia already by 4 weeks of olanzapine therapy (all P < 0.05), with no obvious changes observed in high-density lipoprotein cholesterol (HDL-C) (P > 0.05). In conclusion, olanzapine-induced dyslipidemia, characterized by increased TG, TC, and LDL-C levels, was observed in patients with schizophrenia already by 4 weeks of olanzapine treatment.

Early prediction of clinical response in first episode schizophrenia (FES) patients receiving olanzapine

Background: At present, schizophrenia guidelines recommend waiting for 8 weeks before considering a patient as non-responder. This study aims to detect the optimal early response threshold that best predict the final outcome of olanzapine.Methods: The study was conducted for 8-week, four points follow up (week 2,3,4, and 8) prospective observational study. A reduction of 20, 25, 30% in Positive and Negative Syndrome Scale (PANSS) score from the base line at week 2,3, and 4 respectively were considered as early response. A reduction of 50% at week 8 was considered as responders. Receiver Operating Characteristics (ROC) curves were performed to detect the optimal threshold.Results: Mean total baseline PANSS score was 106.66(95% CI; 100.4, 112.9). Week 2 (AUC = 50.5%, p > 0.964) and week 3 (AUC = 64.9, p > 0.13) responses failed to predict the 8th week response. Week 4 response (AUC = 92%, p < 0.001) can be taken for the prediction of 8th week response (specificity = 72%, sensitivity = 100%, Positive Predictive Value = 61.1%, Negative Predictive Value = 100% and Optimum Early Response (OER) = 29.4%). 25 patients (69%) achieved more than 50% reduction (responders) in PANSS score after 8 weeks of treatment.Conclusions: Our study suggests that patients with early response at week 4 are likely to achieve positive response after 8 weeks. This may help in appropriate clinical decision making for early non-responders.Key PointsThe early response can forecast the outcome at the endpoint for the treatment of FESA reduction of baseline PANSS score by 30% or more after four weeks are likely to have remission after week 8 with olanzapine therapy.

Therapeutic Drug Monitoring of Olanzapine and Cytochrome P450 Genotyping in Nonsmoking Subjects.

The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients. A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic-tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols. Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine. TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.

A platinum black-modified microelectrode for in situ olanzapine detection in microliter volumes of undiluted serum

Olanzapine is a thienobenzodiazepine compound. It is one of the newer types of antipsychotic drugs used in the treatment of schizophrenia and other psychotic disorders. Several methods have been reported for analyzing olanzapine in its pure form or combined with other drugs and in biological fluids. These methods include high-performance liquid chromatography and liquid chromatography-tandem mass spectroscopy. Although many of the reported methods are accurate and sensitive, they require the use of sophisticated equipment, lack in situ analysis, and require expensive reagents. Moreover, several of these methods are cumbersome, require prolonged sample pretreatment, strict control of pH, and long reaction times. Here we present the development of a miniaturized electrochemical sensor that will enable minimally invasive, real-time, and in situ monitoring of olanzapine levels in microliter volumes of serum samples. For this purpose, we modified a microfabricated microelectrode with a platinum black film to increase the electrocatalytic activity of the microelectrode towards olanzapine oxidation; this improved the overall selectivity and sensitivity of the sensor. We observed in recorded voltammograms the anodic current dose response characteristics in microliter volumes of olanzapine-spiked serum samples that resulted in a limit of detection of 28.6 ± 1.3 nM and a sensitivity of 0.14 ± 0.02 µA/cm2 nM. Importantly, the platinum black-modified microelectrode exhibited a limit of detection that is below the clinical threshold (65–130 nM). Further miniaturizing and integrating such sensors into point-of-care devices provide real-time monitoring of olanzapine blood levels; this will enable treatment teams to receive feedback and administer adjustable olanzapine therapy.

P.499 Expression of serotonin receptor 2A alternative isoforms in peripheral blood lymphocytes during olanzapine therapy is modulated by gene polymorphisms rs6311/rs6313

In this paper, we propose a radiation avoiding algorithm of path optimization, aiming to provide a new technical support for radiation protection to professional personnel and robots engage in radiation works in limited and unknown environment. Based on Beetle Antennae Search (BAS) algorithm, radiation perceiving motion model and BAS-based radiation-avoiding algorithm are designed. In view of shortcomings of BAS for radiation avoiding, an improved radiation perceiving motion model and a local perceiving and target-attractive radiation avoiding path optimization algorithm are designed. The proposed algorithms have high computational efficiency and simple process. Besides, a graphical simulation program of the proposed algorithm is established. Comparison results of computer simulation prove effectiveness and feasibility of the proposed algorithms. Experimental results obtained in a simulated environment show that the proposed algorithm could be useful to meet the challenges of radiation avoiding applications that can be described as optimization problems.

Analysis of Gut Microbiota and Their Metabolic Potential in Patients with Schizophrenia Treated with Olanzapine: Results from a Six-Week Observational Prospective Cohort Study.

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5–20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy; in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy.