Olanzapine-treated Patients Research Articles

Double-blind, randomized trial comparing efficacy and safety of continuing olanzapine versus switching to quetiapine in overweight or obese patients with schizophrenia or schizoaffective disorder

We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable, obese, or overweight patients with schizophrenia or schizoaffective disorder. Patients receiving olanzapine were randomized to continuing olanzapine treatment (N =68; 7.5-20 mg/day) or switching to quetiapine (N =65; 300-800 mg/day). Time to relapse was the primary study objective; secondary objectives included changes in weight, metabolic parameters, and psychiatric symptoms, and discontinuation rates. No significant difference in time to relapse was observed (p =0.293), but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group (70.6% vs 43.1%; p =0.002). Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events (AEs) compared to quetiapine (2.94% vs 15.38%, p =0.015). Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m(2). Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13. Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse, but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters.

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up

The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.

Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia

This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects.

Orlistat in Clozapine- or Olanzapine-Treated Patients With Overweight or Obesity

Undesirable metabolic effects of modern antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients. Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005. Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p = .011). There were 5 responders (16.1%) (those with >or= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant. Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population.

Coagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free first-degree relatives

BackgroundClinical studies suggest that the second generation antipsychotics (APs) clozapine and olanzapine and to a lesser extent the typical antipsychotics may be associated with a procoagulant and proinflammatory state that promotes venous thromboembolism. We evaluated here several blood factors associated with coagulation and inflammation in AP-treated schizophrenia patients and their first-degree relatives. MethodsProcoagulant factors (fibrinogen and plasminogen activator inhibitor [PAI-1]), the anticoagulant factor antithrombin III [AT-III], and inflammation-related factors (C-reactive protein [CRP] and leptin) were assessed in patients chronically treated with clozapine (n=29), olanzapine (n=29), typical APs (n=30) and first degree relatives of clozapine (n=23) and olanzapine subjects (n=11). ResultsThe typical AP group had the highest CRP level (p=0.013) in spite of having the lowest body mass index (BMI). Patients as a single group had higher CRP levels than relatives (p=0.003). The typical AP group also had the highest AT-III levels (p=0.021). Fibrinogen levels did not differ between the groups (p=0.13). Olanzapine patients displayed the highest PAI-1 and leptin levels among the drug-treated subjects, but values were similar to those observed in their relatives, and were significantly correlated with the BMI. ConclusionsA homogeneous negative profile of high inflammation and procoagulant factors along with low levels of anticoagulants was not detected in any group. While preliminary, our results suggest that the observed abnormalities were not related to a direct drug effect, but to elevated BMI (high PAI-1 and leptin in olanzapine-treated patients). We speculate that the high CRP in the typical AP group might be related to poor lifestyle habits, but this must we confirmed in future studies.

Effects of risperidone and olanzapine on remnant-like lipoprotein particle cholesterol (RLP-C) in schizophrenic patients

Second generation antipsychotics are associated with the risk of metabolic disorders such as diabetes mellitus and hyperlipidemia. Remnant-like lipoprotein particles cholesterol (RLP-C) are a known risk factor for cardiovascular events. The present study was performed to determine possible differences in fasting blood RLP-C levels between schizophrenic patients treated with risperidone as compared to olanzapine. Patients on olanzapine had significantly higher RLP-C levels than those on risperidone (p < 0.01). In olanzapine-treated patients there was no abnormality in fasting blood glucose levels, but fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) were elevated. RLP-C levels were significantly correlated with plasma triglyceride concentrations in both the olanzapine- (p < 0.01) and risperidone-treated patients (p < 0.01). The regression line slope was greater for the olanzapine group, suggesting a greater influence of olanzapine on RLP-C. There was a significant correlation between RLP-C and HOMA-IR in the risperidone group (p < 0.01) but not in the olanzapine group (p = 0.80). These results suggest that blood glucose monitoring may not be sufficient to detect metabolic disorder and that measurement of RLP-C might be helpful for the screening for metabolic disorders associated with olanzapine therapy.

Open-label treatment with olanzapine in patients with borderline personality disorder

Background and Aims:To evaluate open-label treatment with olanzapine in patients with borderline personality disorder (BPD).Methods:In two concurrent studies, patients received 12 weeks of open-label olanzapine after completing 12-weeks of double-blind treatment with either olanzapine or placebo. Open-label olanzapine dosing started at 2.5 or 5mg/day and could be increased up to 20mg/day (Study 1) or 15mg/day (Study 2).Results:Mean ZAN-BPD total scores decreased from approximately 17 points to approximately 8-10 points during the acute phase. After 12 weeks of open-label olanzapine treatment, mean ZAN-BPD total scores were approximately 6-7 points. Patients treated with placebo during the acute phase and then open-label olanzapine showed changes in weight, prolactin, and other laboratory values similar in magnitude to those seen in acutely olanzapine-treated patients. Patients treated with olanzapine during the acute phase showed smaller changes in weight and laboratory values during the open-label extension.Conclusions:Overall BPD symptom severity was low by the end of the open-label olanzapine treatment period. The types of treatment emergent adverse events appeared to be consistent with those seen previously in patients treated with olanzapine. The direction and magnitude of effects on safety measures depended on the treatment received during the prior double-blind period.

Increased expression of lipid biosynthesis genes in peripheral blood cells of olanzapine-treated patients

Recent in-vitro studies show that antipsychotic drugs increase lipid biosynthesis through changes in gene expression. Based on these finding we compared the expression of two central lipid biosynthesis genes, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD), in whole blood of olanzapine-treated and unmedicated patients. Patients with psychotic disorders were consecutively selected from an ongoing, naturalistic study, and divided into two groups according to the following criteria: (1) strict monotherapy with olanzapine (n=19) or (2) no current medication (n=19). The groups were matched on gender, race and body mass index. Blood lipid levels were examined, and gene expression in whole blood was assessed with quantitative real-time PCR. Expression of FASN (p=0.003) and SCD (p=0.002) was significantly up-regulated in olanzapine-treated compared to unmedicated patients. Transcriptional activation of lipid biosynthesis genes in peripheral blood cells of olanzapine-treated patients suggests a direct lipogenic action of antipsychotic drugs, which may be related to metabolic adverse effects.

321 – Comparison of post-marketing spontaneously reported adverse events in olanzapine-treated adolescent and adult patients

321 – Comparison of post-marketing spontaneously reported adverse events in olanzapine-treated adolescent and adult patients

Association Between HTR2C and HTR2A Polymorphisms and Metabolic Abnormalities in Patients Treated With Olanzapine or Clozapine

Serotonin 2C and 2A receptor (5-HT2C and 5-HT2A) antagonisms are hypothesized to play a role in the metabolic adverse effects induced by olanzapine and clozapine. Associations between polymorphisms in 5-HT2C and 5-HT2A receptor coding genes, HTR2C and HTR2A, with antipsychotic-induced weight gain have been reported. The impact of HTR2C and HTR2A polymorphisms on body mass index (BMI), glucose-insulin homeostasis, and blood lipid levels was evaluated in 46 patients with schizophrenia or schizoaffective disorder and treated with olanzapine (n = 28) or clozapine (n = 18) for at least 6 months. Olanzapine-treated patients with HTR2C haplotype C (-759C, -697C, and 23Ser) had higher BMI (P = 0.029) and C peptide levels (P = 0.029) compared with patients with haplotype B (-759T, -697C, and 23Cys). The frequency of patients homozygous for the HTR2C haplotype A (-759C, -697G, and 23Cys) was significantly higher among clozapine-treated patients with obesity (BMI >/= 30 kg/m) compared with nonobese patients (P = 0.015; odds ratio, 28; 95% confidence interval, 2-380). Patients carrying the HTR2A haplotype 2 (-1438A, 102T, and 452His) had significantly higher C peptide levels compared with haplotype 3 (-1438A, 102T, and 452Tyr) carriers in the olanzapine group (P = 0.034) and in the overall study population (P = 0.019). None of the haplotypes were associated with serum levels of insulin, triglycerides, and cholesterol or with homeostasis model assessment index for insulin resistance. In conclusion, both HTR2C and HTR2A gene polymorphisms seem to be associated with the occurrence of metabolic abnormalities in patients treated with olanzapine or clozapine.

Olanzapine Versus Placebo in the Treatment of Adolescents With Bipolar Mania

The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents. A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure. The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain > or =7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo. Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.

Antipsychotic prescription patterns in outpatient settings: 24-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study

This report describes antipsychotic prescription patterns for outpatients with schizophrenia prescribed olanzapine (n=3222), clozapine (n=236), risperidone (n=1117), quetiapine (n=189) or haloperidol (n=256) monotherapy at study entry and treated in a naturalistic, clinical practice setting over 24 months. Predictive factors associated with remaining on monotherapy were also identified. Olanzapine patients had significantly greater odds of remaining on their initial monotherapy compared to other treatment groups, while clozapine or risperidone recipients were more likely to remain on monotherapy, compared to haloperidol patients. Switching antipsychotic medication was more common than addition of another antipsychotic agent, and the most common reason for modifying treatment was lack of effectiveness. The odds of modifying antipsychotic prescription due to intolerability were lower for patients treated with olanzapine, compared to patients treated with risperidone or haloperidol (p≤.001). However, treatment modification due to patient request was significantly greater for olanzapine-treated patients, compared to risperidone-, quetiapine- or haloperidol-treated patients (p≤.001).

Olanzapine Versus Chlorpromazine in the Treatment of Schizophrenia

This pooled analysis of four 6-week, randomized, open-label, parallel trials of patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) compared the efficacy and tolerability of olanzapine (5-20 mg/d) with those of chlorpromazine (200-800 mg/d). Of the 123 patients randomly allocated to olanzapine (n = 83) or chlorpromazine (n = 40), 109 completed the study (olanzapine, n = 77; chlorpromazine, n = 32). Olanzapine-treated patients showed significantly greater baseline-to-end point mean improvements in the primary efficacy measure, Brief Psychiatric Rating Scale total, compared with chlorpromazine-treated patients (least-squares means: olanzapine, -21.1; chlorpromazine, -10.4; P < 0.001). Response rate was significantly higher in the olanzapine group (66.3% vs. 32.4%; P = 0.001). Baseline-to-maximum changes in the UKU scores for akathisia were significantly different between the groups (P = 0.018). A decrease (improvement) in these scores was observed in 6/74 (8.1%) of olanzapine- and 1/36 (2.8%) chlorpromazine-treated patients. Weight gain was the only common (> or =10%) adverse event that occurred more frequently, although not significantly differently, in the olanzapine group (27.7%) than the chlorpromazine group (12.5%), whereas postural hypotension was the only common adverse event whose occurrence was significantly different between the groups (olanzapine, 0.0%; chlorpromazine, 10.0%; P = 0.010). Both the incidence of > or =7% weight gain from baseline (olanzapine, 26.3%; chlorpromazine, 24.3%) and baseline-to-end point changes in weight (mean +/- SD, kg: olanzapine, 3.41 +/- 3.14; chlorpromazine, 2.81 +/- 2.65) were not significantly different between the treatment groups. Baseline-to- end point changes in nonfasting glucose differed significantly between the groups (mean +/- SD, mmol/L: olanzapine, 0.09 +/- 1.11; chlorpromazine, 0.72 +/- 2.04; P = 0.042). This analysis suggests that, compared with chlorpromazine, olanzapine may be more efficacious and have a more favorable tolerability profile in treating patients with schizophrenia.

Olanzapine therapy in anorexia nervosa: psychobiological effects

Dopamine impairments occur in anorexia nervosa. The aim of this study was to see whether treatment with the atypical dopamine antagonist antipsychotic olanzapine improves the disorder. Thirty anorexics, 18 restricted and 12 bingeing-purging, underwent a 3-month course of cognitive behavioral therapy, plus at random and double-blinded oral olanzapine (2.5 mg for 1 month, 5 mg for 2 months) in half and oral placebo in the other half of them. BMI, psychopathological aspects (eating disorder inventory, Hamilton Rating Scale, Buss-Durkee Rating Scale, Yale Brown Cornell for Eating Disorders Rating Scale, temperament-character inventory), and homovanillic acid blood concentrations for dopamine secretion, were monitored at baseline and then monthly during the trial. At the end of the trial BMI, total eating disorder inventory, total Yale Brown Cornell for Eating Disorders Rating Scale, Buss-Durkee Rating Scale, Hamilton Rating Scale scores and in olanzapine-treated patients the subitems of eating disorder inventory ineffectiveness and maturity fear, of Buss-Durkee Rating Scale direct aggressiveness, of temperament-characteristic inventory persistence had improved significantly. When stratified for anorexia nervosa subtype, BMI changes were significant among anorexia nervosa bingeing-purging patient, 'depression' (Hamilton Rating Scale) and 'direct aggressiveness' (Buss-Durkee Rating Scale) among anorexia nervosa bingeing-purging patients, 'persistence' (temprerament-characteristic inventory), among anorexics restricted patients, with a trend toward significance for obsessivity-compulsivity (Yale Brown Cornell for Eating Disorders Rating Scale). homovanilic acid blood levels increased significantly in the cognitive behavioral therapy+olanzapine group. No correlations were observed between homovanilic acid concentrations and psychopathological parameters. The pharmacological treatment can significantly improve specific aspects of anorexia nervosa.

Weight Changes During Treatment With Olanzapine in Older Adult Patients With Dementia and Behavioral Disturbances

Treatment-emergent weight gain has been reported in younger patients receiving atypical antipsychotics, but less is known about weight gain in adults aged 65 years and older. This was a post hoc analysis of 1267 patients with dementia and behavioral disturbances treated with olanzapine (1 to 20 mg/d) in clinical trials, most of whom were underweight (body mass index <18.5 kg/m2) or of normal weight (body mass index, 18.5-24.9 kg/m2) at baseline. Weight changes over the first 20 weeks of treatment in olanzapine-treated patients, as estimated by a repeated measures analysis model, were significantly greater in the combined categories of underweight and normal weight (1.22 kg and 1.29 kg, respectively) versus overweight and obese (0.56 kg and 0.53 kg, respectively; P = .006). The estimated probability of gaining more than 7% of initial body weight was significantly greater in patients treated with olanzapine versus active comparator (P < .001) or placebo (P < .001). Weight gain in olanzapine-treated older patients with dementia and behavioral disturbances was significantly greater in individuals with a baseline body mass index of less than 25 kg/m2.

Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: A multicentric, double-blind, placebo-controlled trial

Background Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables. Methods Eighty patients taking olanzapine (5–20 mg daily for more than 4 consecutive months) were randomly allocated to metformin ( n = 40; 850 to 2550 mg daily) or placebo ( n = 40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment. Results The metformin group lost 1.4 ± 3.2 kg ( p = 0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: − 0.18 ± 2.8 kg ( p = 0.7). The HOMA-IR significantly increased after placebo ( p = 0.006) and did not change after metformin ( p = 0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels. Conclusions Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.

A Randomized Controlled Trial of Olanzapine Versus Haloperidol in the Treatment of Primary Negative Symptoms and Neurocognitive Deficits in Schizophrenia

Primary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms. Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were randomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study ran from September 1998 through May 2005. There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p <or=.05), with an 8.63-point decrease in the olanzapine group (t = 5.66, df = 1,33; p <or=.05), and PANSS total score (t = 9.304, df = 1,33; p <or=.05). Linear mixed model for repeated measures indicated that the olanzapine group showed a statistically significant change in negative symptom scores (F = 9.70, df = 1,15; p <or=.05). There were no significant differences for change in PANSS positive score, PANSS general psychopathology score, and HAM-D score. Using a criterion of 40% decrease in the PANSS negative subscale score, 31.25% of patients were classified as responders in the olanzapine group, while only 10.53% were responders in the haloperidol group. There were no significant between-treatment differences in the incidence of extrapyramidal side effects. Olanzapine-treated patients experienced more weight gain than the haloperidol-treated group (F = 7.044, df = 1,33; p <or=.05). Neuropsychological Results: Significant differences in change from baseline to endpoint for the olanzapine-treated group were seen for declarative verbal learning memory (F = 11.499, df = 1,14; p = .021) and the motor functioning domain (F = 4.405, df = 1,31; p = .044). The results of this study suggest that olanzapine treatment was associated with significant improvement in primary negative symptoms, overall symptomatic improvement as measured by the PANSS total score, and improvement in some areas of neurocognition as compared with haloperidol/benztropine mesylate treatment.

Olanzapine for the treatment of borderline personality disorder: A flexible-dose 12-week randomized double-blind placebo-controlled study

Objective:We examined the efficacy and safety of flexibly-dosed olanzapine for the treatment of borderline personality disorder (BPD).Methods:In this 12-week double-blind trial, patients 18-65 years of age with a diagnosis of DSM-IV BPD received olanzapine (2.5-20mg/day; N=155) or placebo (N=159). The primary efficacy measure was the change from baseline to last-observation carried forward endpoint (LOCF) on the Zanarini Rating Scale for BPD (ZAN-BPD) total score. Rate of response and time to response were also examined, with response defined as a >=50% reduction in ZAN-BPD total score.Results:Mean baseline ZAN-BPD total scores were indicative of moderate symptom severity (olanzapine 17.01 vs. placebo 17.70, p=0.156). Both treatment groups showed significant improvements in overall symptom severity, based on mean changes from baseline to LOCF endpoint in ZAN-BPD total score, but did not differ in the magnitude of improvement at endpoint (olanzapine -6.56 vs. placebo -6.25, p=.661). Response rates did not differ between treatment groups (olanzapine 64.7% vs. placebo 53.5%, p=.062); however, time to response was significantly shorter for the olanzapine treatment group (p=.022). Treatment-emergent adverse events reported significantly more frequently among olanzapine-treated patients included somnolence, sedation, increased appetite and weight increase. Mean weight change from baseline to endpoint was significantly different for olanzapine- relative to placebo-treated patients (2.86vs. -0.35kg, p<.001).Conclusions:Both the olanzapine- and placebo-treated patients showed significant but not statistically different improvement on overall symptoms of borderline personality disorder. The types of adverse events observed with olanzapine treatment were similar to those seen previously in adult populations.

Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients.

In the present study, we examined the effects of olanzapine on plasma levels of catecholamine metabolites, brain-derived neurotrophic factor, and cytokines (interleukin-2, interleukin-6 and tumor necrosis factor-alpha) using 32 olanzapine-treated schizophrenic patients and age and sex-matched 55 healthy individuals. Treatment with olanzapine for 8 weeks improved both positive and negative symptoms of schizophrenia. It also increased the plasma 3-methoxy-4-hydroxyphenylglycol levels, which were associated with the changes in the total scores of negative symptoms measured on the Positive and Negative Symptom Scale, and decreased the plasma homovanillic acid levels. In addition, treatment with olanzapine for 8 weeks reduced the plasma interleukin-2 levels. In contrast, olanzapine did not alter the plasma levels of brain-derived neurotrophic factor, interleukin-6, or tumor necrosis factor-alpha. These results suggest that olanzapine influences the dynamics of catecholamine and interleukin-2, which might be associated with its clinical efficacy.

Differential Rates of Treatment Discontinuation in Clinical Trials as a Measure of Treatment Effectiveness for Olanzapine and Comparator Atypical Antipsychotics for Schizophrenia

Antipsychotic treatment discontinuation can be used to measure overall treatment effectiveness. Our goal was to investigate differential treatment discontinuation comparing olanzapine with other atypical antipsychotics. A post hoc pooled analysis of 4 randomized, double-blind, 24- to 28-week schizophrenia clinical trials included 822 olanzapine-treated and 805 risperidone-, quetiapine-, or ziprasidone-treated patients. A checklist was used to record the reason for discontinuation. Treatment differences were assessed between olanzapine and the other 3 antipsychotics combined. Poor response/symptom worsening was the primary reason for discontinuation, regardless of medication. The rate of discontinuation due to poor response/symptom worsening significantly varied by treatment (olanzapine, 14.23%, vs. other atypical antipsychotics, 24.60%; P < 0.0001). The rate of discontinuation due to intolerability of medication did not significantly vary by treatment (olanzapine, 5.60%, vs. other atypical antipsychotics, 7.45%; P = 0.13). Consequent to the differential rates of discontinuation due to poor response/symptom worsening, the olanzapine-treated patients experienced a significantly greater likelihood of overall treatment completion (53.9% vs. 39.3%; P < 0.001) and a significantly longer duration of treatment (19.1 vs. 16.1 weeks; P < 0.0001) than other atypical-treated patients. The predominant reason for the significantly lower discontinuation rate of treatment for patients taking olanzapine compared with that of patients taking other atypical antipsychotics was the significantly higher dropout rates in other atypical antipsychotics because of poor response/symptom worsening.