Olanzapine-treated Patients Research Articles

Revisiting diabetes risk of olanzapine versus aripiprazole in serious mental illness care.

Exposure to second-generation antipsychotics (SGAs) carries a risk of type 2 diabetes, but questions remain about the diabetogenic effects of SGAs. To assess the diabetes risk associated with two frequently used SGAs. This was a retrospective cohort study of adults with schizophrenia, bipolar I disorder or severe major depressive disorder (MDD) exposed during 2008-2013 to continuous monotherapy with aripiprazole or olanzapine for up to 24 months, with no pre-period exposure to other antipsychotics. Newly diagnosed type 2 diabetes was quantified with targeted minimum loss-based estimation; risk was summarised as the restricted mean survival time (RMST), the average number of diabetes-free months. Sensitivity analyses were used to evaluate potential confounding by indication. Aripiprazole-treated patients had fewer diabetes-free months compared with olanzapine-treated patients. RMSTs were longer in olanzapine-treated patients, by 0.25 months [95% CI: 0.14, 0.36], 0.16 months [0.02, 0.31] and 0.22 months [0.01, 0.44] among patients with schizophrenia, bipolar I disorder and severe MDD, respectively. Although some sensitivity analyses suggest a risk of unobserved confounding, E-values indicate that this risk is not severe. Using robust methods and accounting for exposure duration effects, we found a slightly higher risk of type 2 diabetes associated with aripiprazole compared with olanzapine monotherapy regardless of diagnosis. If this result was subject to unmeasured selection despite our methods, it would suggest clinician success in identifying olanzapine candidates with low diabetes risk. Confirmatory research is needed, but this insight suggests a potentially larger role for olanzapine in the treatment of well-selected patients, particularly for those with schizophrenia, given the drug's effectiveness advantage among them.

Artificial intelligence and virtual reality applied to the clinical care of women with schizophrenia: A systematic review.

IntroductionArtificial intelligence (AI) and virtual reality (VR) are useful tools that can improve precision medicine and can prove useful in the clinical care of patients with psychosis.ObjectivesOur aim was to determine whether AI and VR have been applied to the prediction of clinical response in women with schizophrenia.Methods A systematic review was carried out in PubMed and Scopus from inception to September 2023 by using the PRISMA guidelines. Search terms: (“artificial intelligence” OR “intelligent support” OR “machine intelligence” OR “machine learning” OR “virtual reality” OR “intelligent agent” OR “neural networks” OR “virtual reality” OR “digital twins”) AND (“schizophrenia” OR “psychosis”) AND (“women” OR gender”). Inclusion criteria: 1)English, French, German or Spanish language, 2) reporting treatment response in schizophrenia (as long as information in women was included), and 3) including AI and VR techniques.ResultsFrom a total of 320 abstracts initially screened (PubMed:182, Scopus:138), we selected 6 studies that met criteria. -Prediction of treatment response. (1) Clinical information, genetic risk score and proxy methylation score have been shown to improve prediction models. (2) Graph-theory-based measures have been combined with machine learning.-Therapeutic drug monitoring. (1) A machine learning model has been useful in predicting quetiapine blood concentrations.-Pharmacovigilance. (1) Machine learning has connected prolactin levels and response in olanzapine-treated patients. (Zhu et al., 2022).-Treatment-resistant schizophrenia (TRS). (1) Women with TRS have been found to receive clozapine less frequently than men (adjusted for sociodemographic, biological and clinical factors). (2) Statistical learning approach: Women have been found to respond better to clozapine than men. ConclusionsAI, including machine learning, show promising results in the prediction of treatment response in women with schizophrenia. As of yet, digital twins have not been investigated to test specific interventions or to personalize treatment in women with schizophrenia.Disclosure of InterestNone Declared

Effects of CYP2D6 gene polymorphism on plasma concentration and therapeutic effect of olanzapine

This study aimed to evaluate the relationship between gene polymorphisms of metabolic enzymes, particularly the CYP2D6 gene, and the plasma concentration of olanzapine, as well as treatment response in patients with chronic schizophrenia. We recruited olanzapine-treated patients and examined their plasma olanzapine levels. Additionally, a common mutation site within each of the nine exons of the full-length CYP2D6 sequence was assayed. The Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Overall Clinical Impression were used to assess schizophrenic symptoms, whereas the Barnes Akathisia Scale and Extrapyramidal Symptom Rating Scale were used to evaluate adverse effects. The results showed no significant differences in plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects among different CYP2D6 genotypes. However, an association between olanzapine concentrations and improvement in clinical symptoms and adverse reactions was observed. In conclusion, the CYP2D6 genotype did not significantly impact plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects.

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry)

IntroductionClozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited...

Integrating machine learning with electronic health record data to facilitate detection of prolactin level and pharmacovigilance signals in olanzapine-treated patients.

Background and aimAvailable evidence suggests elevated serum prolactin (PRL) levels in olanzapine (OLZ)-treated patients with schizophrenia. However, machine learning (ML)-based comprehensive evaluations of the influence of pathophysiological and pharmacological factors on PRL levels in OLZ-treated patients are rare. We aimed to forecast the PRL level in OLZ-treated patients and mine pharmacovigilance information on PRL-related adverse events by integrating ML and electronic health record (EHR) data.MethodsData were extracted from an EHR system to construct an ML dataset in 672×384 matrix format after preprocessing, which was subsequently randomly divided into a derivation cohort for model development and a validation cohort for model validation (8:2). The eXtreme gradient boosting (XGBoost) algorithm was used to build the ML models, the importance of the features and predictive behaviors of which were illustrated by SHapley Additive exPlanations (SHAP)-based analyses. The sequential forward feature selection approach was used to generate the optimal feature subset. The co-administered drugs that might have influenced PRL levels during OLZ treatment as identified by SHAP analyses were then compared with evidence from disproportionality analyses by using OpenVigil FDA.ResultsThe 15 features that made the greatest contributions, as ranked by the mean (|SHAP value|), were identified as the optimal feature subset. The features were gender_male, co-administration of risperidone, age, co-administration of aripiprazole, concentration of aripiprazole, concentration of OLZ, progesterone, co-administration of sulpiride, creatine kinase, serum sodium, serum phosphorus, testosterone, platelet distribution width, α-L-fucosidase, and lipoprotein (a). The XGBoost model after feature selection delivered good performance on the validation cohort with a mean absolute error of 0.046, mean squared error of 0.0036, root-mean-squared error of 0.060, and mean relative error of 11%. Risperidone and aripiprazole exhibited the strongest associations with hyperprolactinemia and decreased blood PRL according to the disproportionality analyses, and both were identified as co-administered drugs that influenced PRL levels during OLZ treatment by SHAP analyses.ConclusionsMultiple pathophysiological and pharmacological confounders influence PRL levels associated with effective treatment and PRL-related side-effects in OLZ-treated patients. Our study highlights the feasibility of integration of ML and EHR data to facilitate the detection of PRL levels and pharmacovigilance signals in OLZ-treated patients.

Olanzapine-associated dose-dependent alterations for weight and metabolic parameters in a prospective cohort.

Metabolic abnormalities have been associated with olanzapine treatment. We assessed if olanzapine has dose‐dependent effects on metabolic parameters with changes for weight, blood pressure, lipid and glucose profiles being modelled using linear mixed‐effects models. The risk of metabolic abnormalities including early weight gain (EWG) (≥5% during first month) was assessed using mixed‐effects logistic regression models. In 392 olanzapine‐treated patients (median age 38.0 years, interquartile range [IQR] = 26.0–53.3, median dose 10.0 mg/day, IQR = 5.0–10.0 for a median follow‐up duration of 40.0 days, IQR = 20.7–112.2), weight gain was not associated with olanzapine dose (p = 0.61) although it was larger for doses versus ≤10 mg/day (2.54 ± 5.55 vs. 1.61 ± 4.51% respectively, p = 0.01). Treatment duration and co‐prescription of >2 antipsychotics, antidepressants, benzodiazepines and/or antihypertensive agents were associated with larger weight gain (p < 0.05). Lower doses were associated with increase in total and HDL cholesterol and systolic and diastolic blood pressure (p < 0.05), whereas higher doses were associated with glucose increases (p = 0.01). Patients receiving >10 mg/day were at higher EWG risk (odds risk: 2.15, 1.57–2.97). EWG might be prominent in high‐dose olanzapine‐treated patients with treatment duration and co‐prescription of other medications being weight gain moderators. The lack of major dose‐dependent patterns for weight gain emphasizes that olanzapine‐treated patients are at weight gain risk regardless of the dose.

Association of 5-HTR2A T102C and A-1438G polymorphisms with clinical response to atypical antipsychotic treatment in schizophrenia: A meta-analysis

Associations of serotonin 2A receptor (5-HTR2A) gene polymorphisms with clinical response to atypical antipsychotics (AAPs) treatment in schizophrenia (SCZ) were inconsistent. Thus we conducted a meta-analysis to investigate more reliable estimates. The Cochrane Library, Embase, PubMed, Weipu, CNKI and Wanfang databases were searched for eligible studies published up to September 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in four genetic models. Subgroup analyses were performed by ethnicity and antipsychotic type. Meta-regression was used to evaluate the potential effects of confounding variables. In total, 19 studies were included for the meta-analysis, of which 17 studies containing 2359 patients were identified for T102C polymorphism and 7 studies containing 1408 patients for A-1438G polymorphism. The results showed that A-1438G polymorphism was significantly associated with clinical response to AAPs treatment in SCZ in four genetic models (allele model, A vs. G, OR = 1.87, 95% CI = 1.05–3.33, P = 0.034; recessive model, AA vs. GA + GG: OR = 1.79, 95% CI = 1.17–2.72, P = 0.007; dominant model, AA + GA vs. GG: OR = 3.40, 95% CI = 1.15–10.10, P = 0.027; co-dominant model, AA vs. GG: OR = 3.44, 95% CI = 1.07–11.10, P = 0.039) in Asians, but not in Caucasians. When stratified by antipsychotic type, A-1438G polymorphism was related to the efficacy of olanzapine in recessive model (AA vs. GA + GG, OR = 1.85, 95% CI = 1.18–2.90, P = 0.007), but not in other models. However, neither four genetic models nor subgroup analyses of T102C polymorphism were found any significant associations with AAPs response (P > 0.05). Meta-regression revealed that no association was confounded by mean age, male ratio, treatment duration and illness duration (P > 0.05). The present meta-analysis indicated that 5-HTR2A A-1438G polymorphism, but not T102C polymorphism, was significantly associated with AAPs response in SCZ, especially in Asians and olanzapine-treated patients.

A meta-analysis comparing short-term weight and cardiometabolic changes between olanzapine/samidorphan and olanzapine

This study compared weight and cardiometabolic changes after short-term treatment of olanzapine/samidorphan and olanzapine. Eligible criteria for an included trial were ≤ 24 weeks, randomized controlled trials (RCTs) that compared olanzapine/samidorphan and olanzapine treatments in patients/healthy volunteers and reported weight or cardiometabolic outcomes. Three databases were searched on October 31, 2020. Primary outcomes included weight changes and all-cause dropout rates. Standardized mean differences (SMDs) and risk ratios (RRs) were computed and pooled using a random-effect model. This meta-analysis included four RCTs (n = 1195). The heterogeneous data revealed that weight changes were not significantly different between olanzapine/samidorphan and olanzapine groups (4 RCTs, SDM = − 0.19, 95% CI − 0.45 to 0.07, I2 = 75%). The whole-sample, pooled RR of all-cause dropout rates (4 RCTs, RR = 1.02, 95% CI 0.84 to 1.23, I2 = 0%) was not significant different between olanzapine/samidorphan and olanzapine groups. A lower percentage of males and a lower initial body mass index were associated with the greater effect of samidorphan in preventing olanzapine-induced weight gain. Current evidence is insufficient to support the use of samidorphan to prevent olanzapine-induced weight gain and olanzapine-induced cardiometabolic abnormalities. Samidorphan is well accepted by olanzapine-treated patients.

Binge Eating Disorders in Antipsychotic-Treated Patients With Schizophrenia: Prevalence, Antipsychotic Specificities, and Changes Over Time.

Excessive energy intake likely favors metabolic dysfunction in patients with schizophrenia and may be, in part, the consequence of antipsychotic treatments. However, previous studies on the prevalence of bulimia and binge eating symptoms in antipsychotic-treated patients are contradictory and not sufficiently informative. The prevalence of bulimia nervosa, binge eating disorder, and subsyndromal binge eating disorder was studied using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria in 156 patients with schizophrenia or schizoaffective disorder treated with antipsychotic monotherapy. The effects of different antipsychotics were compared. The prevalence of full syndromal binge eating disorder was 4.4% and that of subsyndromal binge eating disorder was 18.7% in patients (23.1% for binge eating spectrum disorder), and there were no cases of bulimia nervosa. Compared with the whole sample, binge eating spectrum disorders were significantly more prevalent in clozapine- and olanzapine-treated patients. Comparisons of patients having undergone treatment for 2 years or less with patients treated for more than 2 years showed that binge eating spectrum disorders decrease significantly over time, the difference being significant in clozapine- and olanzapine-treated patients. Night eating, simply assessed by a single question, showed a prevalence of 30% and was more prevalent in women treated with clozapine and olanzapine, with no significant change over time. Binge eating disorders should be considered as important factors involved in the development of weight gain and metabolic syndrome in antipsychotic-treated patients with schizophrenia. The difficulty to reliably assess binge eating spectrum disorders in patients with psychosis is highlighted.

Relationship between metabolic syndrome and acylated/desacylated ghrelin ratio in patients with schizophrenia under olanzapine medication.

Ghrelin is a peptide hormone that mediates glucose homeostasis and lipid metabolism. Acylated ghrelin (AG) and desacylated ghrelin (DAG) are the two main forms of ghrelin, which have opposing roles in energy homeostasis. The AG/DAG ratio has been proposed to be associated with metabolic syndrome (MetS) in the general population. This study compared the relationships between MetS and ghrelin parameters in patients with schizophrenia. Patients diagnosed with schizophrenia and under olanzapine monotherapy were recruited. Fasting blood samples were collected for the analyses of metabolic and ghrelin parameters. The serum levels of total ghrelin and AG were measured by enzyme-linked immunosorbent assay kits. DAG level was calculated by subtracting the AG level from the total ghrelin level. We recruited 151 subjects with schizophrenia, and classified them into those with MetS (n = 41) and those without MetS (n = 110). Subjects with MetS had a significantly higher AG/DAG ratio, as well as lower total ghrelin and DAG levels. There were no sex differences in ghrelin parameters. The AG/DAG ratio was significantly and positively correlated with weight, body mass index, waist circumference, insulin level, homeostasis model assessment of insulin resistance and number of MetS components. Multiple linear regression analysis indicated that the number of MetS components remained significantly associated with the AG/DAG ratio. Our results revealed that lower AG/DAG ratios were associated with better metabolic profiles in olanzapine-treated patients with schizophrenia. These observations suggest that the balance between AG and DAG plays a crucial role in the metabolic homeostasis among patients with schizophrenia.

The Effect of Valproic Acid on Olanzapine Serum Concentration: A Study Including 2791 Patients Treated With Olanzapine Tablets or Long-Acting Injections.

The combination of olanzapine and valproic acid (VPA) is regularly prescribed in the treatment of bipolar or schizoaffective disorders. The VPA has been shown to reduce olanzapine concentration, but the mechanism behind this interaction remains unknown. We aimed to investigate the effect of VPA on olanzapine concentration during oral versus long-acting injectable (LAI) formulation in a real-life setting. From a therapeutic drug monitoring service, prescribed doses and serum concentrations from 2791 olanzapine-treated patients (9433 measurements) were included. The number of patients on olanzapine-LAI treatment was 328, whereas 2463 were using oral olanzapine. The frequency of patients comedicated with VPA was 9.4% for olanzapine tablets and 5.8% for olanzapine-LAI. The VPA had no effect on olanzapine dose-adjusted concentrations in LAI users (1.6 vs 1.7 [ng/mL]/[mg/d]; P = 0.38), whereas in the oral group the dose-adjusted olanzapine concentration was lower in VPA users (2.2 vs 2.7 [ng/mL]/[mg/d]; P < 0.001). For smokers in the oral olanzapine group using VPA, 8.7% of the measurements were in the subtherapeutic range (<10 ng/mL) compared with 6.0% in nonusers (P = 0.003). These findings show that the VPA-olanzapine interaction involves a presystemic mechanism and is therefore restricted to oral olanzapine treatment. For oral treatment of olanzapine, comedication with VPA implies a risk of insufficient effect, which may be of clinical relevance in smokers in particular. Thus, it is important to be aware of the interaction potential with VPA during oral olanzapine use, whereas for LAI-treated patients fewer precautions are required from a pharmacokinetic point of view.

Adjunctive telmisartan treatment on body metabolism in clozapine or olanzapine treated patients with schizophrenia: a randomized, double blind, placebo controlled trial.

This study examined the effect of adjunctive telmisartan on body metabolism in clozapine- or olanzapine-treated patients with schizophrenia. Each subject had been on stable dose of olanzapine or clozapine for at least 1month. In a 12-week randomized, double-blind, placebo-controlled study, subjects received either telmisartan (80mg once per day) or placebo. The homeostasis model of assessment of insulin resistance (HOMA-IR) was calculated based on fasting blood levels of insulin and glucose. Fasting blood levels of triglycerides and cholesterols, as well as serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were measured. The whole-body dual-energy X-ray absorptiometry (DXA) was used to assess body composition. Lipid particles were assessed using nuclear magnetic resonance (NMR) spectroscopy. All assessments were conducted at baseline and repeated at week 12. Fifty-four subjects were randomized and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). There were no significant differences between the two groups in week 12 changes for HOMA-IR or fasting triglycerides (- 0.18 ± 1.24 vs 0.39 ± 1.39, p = 0.181; - 26 ± 76 vs - 10 ± 81mg/dL, p = 0.679, respectively) (telmisartan vs placebo). Further, there were no significant between group differences in week 12 changes for other fasting lipids, body weight, body mass index, waist circumference, as well as various measures of lipid particles (p's > 0.100). The DXA assessment showed no significant differences between the two groups in week 12 changes for fat mass, lean mass, or total mass (p's > 0.100). In the present study, adjunctive treatment of telmisartan did not seem to improve body metabolism in schizophrenia patients receiving olanzapine or clozapine. The implications for future studies were discussed. CLINICALTRIALS. NCT00981526.

High prevalence of prediabetes and metabolic abnormalities in overweight or obese schizophrenia patients treated with clozapine or olanzapine.

To assess the prevalence of prediabetes and metabolic abnormalities among overweight or obese clozapine- or olanzapine-treated schizophrenia patients, and to identify characteristics of the schizophrenia group with prediabetes. A cross-sectional study assessing the presence of prediabetes and metabolic abnormalities in schizophrenia clozapine- or olanzapine-treated patients with a body mass index (BMI) ≥27 kg/m2. Procedures were part of the screening process for a randomized, placebo-controlled trial evaluating liraglutide vs placebo for improving glucose tolerance. For comparison, an age-, sex-, and BMI-matched healthy control group without psychiatric illness and prediabetes was included. Prediabetes was defined as elevated fasting plasma glucose and/or impaired glucose tolerance and/or elevated glycated hemoglobin A1c. Among 145 schizophrenia patients (age = 42.1 years; males = 59.3%) on clozapine or olanzapine (clozapine/olanzapine/both: 73.8%/24.1%/2.1%), prediabetes was present in 69.7% (101 out of 145). While schizophrenia patients with and without prediabetes did not differ regarding demographic, illness, or antipsychotic treatment variables, metabolic abnormalities (waist circumference: 116.7±13.7 vs 110.1±13.6 cm, P = 0.007; triglycerides: 2.3±1.4 vs 1.6±0.9 mmol/L, P = 0.0004) and metabolic syndrome (76.2% vs 40.9%, P<0.0001) were significantly more pronounced in schizophrenia patients with vs without prediabetes. The age-, sex-, and BMI-matched healthy controls had significantly better glucose tolerance compared to both groups of patients with schizophrenia. The healthy controls also had higher levels of high-density lipoprotein compared to patients with schizophrenia and prediabetes. Prediabetes and metabolic abnormalities were highly prevalent among the clozapine- and olanzapine-treated patients with schizophrenia, putting these patients at great risk for later type 2 diabetes and cardiovascular disease. These results stress the importance of identifying and adequately treating prediabetes and metabolic abnormalities among clozapine- and olanzapine-treated patients with schizophrenia.

Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics.

ObjectiveRecent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants.MethodsWe assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of PON1 gene (Q192R, L55M, −108C>T).ResultsWe found significantly lower (−13.3%) AREase activity in schizophrenic patients, along with significantly lower (−18.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and −108C>T polymorphisms distributions were similar.ConclusionWe identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.

Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder

Compared with the general population, patients with schizophrenia have a 2- to 3-fold higher mortality rate primarily caused by cardiovascular disease. Previous interventions designed to counteract antipsychotic-induced weight gain and cardiometabolic disturbances reported limited effects. To determine the effects of the glucagon-like peptide-1 receptor agonist liraglutide added to clozapine or olanzapine treatment of schizophrenia spectrum disorders. This randomized clinical double-blind trial enrolled participants at 2 clinical sites in Denmark. Of 214 eligible participants with a schizophrenia spectrum disorder, 103 were randomized to liraglutide or placebo. Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and had prediabetes. Data were collected from May 1, 2013, through February 25, 2016. Treatment for 16 weeks with once-daily subcutaneous injection of liraglutide or placebo. Trial drug therapy was titrated during the first 2 weeks of the study. The primary end point was change in glucose tolerance estimated by a 75-g oral glucose tolerance test result. Secondary end points included change in body weight and cardiometabolic parameters. Of the 103 patients undergoing randomization (60 men [58.3%] and 43 women [41.7%]), 97 were included in the efficacy analysis, with a mean (SD) age of 42.5 (10.5) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 33.8 (5.9). The liraglutide and placebo groups had comparable characteristics (mean [SD] age, 42.1 [10.7] vs 43.0 [10.5] years; 30 men in each group; mean [SD] body mass index, 33.7 [5.1] vs 33.9 [6.6]). A total of 96 randomized participants (93.2%) completed the trial. Glucose tolerance improved in the liraglutide group compared with the placebo group (P < .001). Altogether, 30 liraglutide-treated participants (63.8%) developed normal glucose tolerance compared with 8 placebo-treated participants (16.0%) (P < .001; number needed to treat, 2). Body weight decreased with liraglutide compared with placebo (-5.3 kg; 95% CI, -7.0 to -3.7 kg). Reductions in waist circumference (-4.1 cm; 95% CI, -6.0 to -2.3 cm), systolic blood pressure (-4.9 mm Hg; 95% CI, -9.5 to -0.3 mm Hg), visceral fat (-250.19 g; 95% CI, -459.9 to -40.5 g), and low-density lipoprotein levels (-15.4 mg/dL; 95% CI, -23.2 to -7.7 mg/dL) occurred with liraglutide compared with placebo. Adverse events with liraglutide affected mainly the gastrointestinal tract. Liraglutide significantly improved glucose tolerance, body weight, and cardiometabolic disturbances in patients with schizophrenia spectrum disorders treated with clozapine or olanzapine. clinicaltrials.gov Identifier: NCT01845259.

SU89. Cortical Thickness and Gray/White Matter Contrast in Olanzapine-Treated and Unmedicated Psychosis Patients and in Healthy Controls: A Moderating Role of HDL Cholesterol

SU89. Cortical Thickness and Gray/White Matter Contrast in Olanzapine-Treated and Unmedicated Psychosis Patients and in Healthy Controls: A Moderating Role of HDL Cholesterol

Role of olanzapine in chemotherapy-induced nausea and vomiting on platinum-based chemotherapy patients: a randomized controlled study.

Even with the use of modern antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) is still a cause of great distress to the patients. Olanzapine, primarily marketed as an antipsychotic, was found to reduce nausea and vomiting in some chemotherapy patients. But it was never tested in Indian population with a diverse genetic background. The present study aims to evaluate the role of olanzapine in CINV in patients receiving platinum-based chemotherapy. The study was a randomized, controlled, assessor-blinded study on 100 chemotherapy-naïve consenting patients receiving any one from cisplatin, carboplatin or oxaliplatin. The control group (n=50) received palonosetron and dexamethasone in the approved therapeutic dose from the day 1 of chemotherapy. The test group (n=50) received additional olanzapine 10mg/day from day 1 for five consecutive days. CINV and quality of life (QoL) were assessed. Vomiting was significantly less among the olanzapine-treated patients. Control of delayed emesis was significantly better in this group (complete response among 96 vs. 42% in the control group, p value <0.0001). Incidence and severity of nausea was significantly less in this group. Failure of anti-CINV measure was 4% in this group compared to 26% of the patients of the control group duringoverall days 1-5. Though sedation was more in these olanzapine-treated patients, there was no dose-limiting adverse event. Quality of life was also better among the olanzapine-treated patients. Olanzapine was found to be effective as add-on in the control of CINV.

Is there an interrelationship between the effects of antipsychotics on psychopathology and on metabolism?

Background: Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications. Aim: To explore whether the decreased body weight in these patients is associated with a worsened psychopathology. Methods: In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test. Results: Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores. Conclusions: Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.