Olanzapine Group Research Articles

Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium

Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear. To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention. PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018. Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention. To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model. The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium. A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control. This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.

26 A Phase 3 Study to Determine the Antipsychotic Efficacy and Safety of ALKS 3831 in Adult Patients with Acute Exacerbation of Schizophrenia

AbstractBackgroundALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.Study objectiveTo assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.MethodsThis was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).ResultsOf 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.DiscussionTreatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.Funding Acknowledgements: This study was funded by Alkermes, Inc.

A comparative study of the efficacy of amisulpride and olanzapine in patients with schizophrenia attending the outpatient Department of Psychiatry in a tertiary care hospital, Silchar, Assam, India

Background: Schizophrenia is one of the most commonly encountered psychiatric disorders. It is characterized by impairment in perception or expression of reality, leading to occupational and social dysfunction. Now a day’s mainstay of treatment of schizophrenia is by using atypical antipsychotics. Amisulpride and olanzapine are atypical antipsychotics which are commonly used in treatment of schizophrenia. The current study is undertaken to assess the efficacy of amisulpride which is a relatively newer antipsychotics against existing antipsychotic olanzapine.Methods: This was designed as a single-blind, prospective, parallel-group, observational study. Eighty adult patients of either sex were randomized to receive standard doses of the two drugs orally for 12 weeks, with follow up at 4 and 8 weeks. Effectiveness was assessed by change in the score of Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) score during the treatment period. Data were entered in Microsoft excel and statistical analysis were done using graph pad and p value <0.05 considered to be statistically significant.Results: Out of 80 adults patients 76 patients were evaluated by dividing into two groups, 38 patients were included in each group. Final BPRS score was less for olanzapine as compared to amisulpride (p<0.001). Improvement in CGI score is more in olanzapine group than amisulpride group which became statistically significant from 8th weeks onwards.Conclusions: Both amisulpride and olanzapine are very effective in controlling the symptoms of schizophrenia which is evident by significant decrease in BPRS, CGI-S and CGI-I score, but efficacy of amisulpride is still inferior to olanzapine.

Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial.

This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. This randomized double-blind placebo-controlled trial of adult outpatients with anorexia nervosa (N=152, 96% of whom were women; the sample's mean body mass index [BMI] was 16.7) was conducted at five sites in North America. Participants were randomly assigned in a 1:1 ratio to receive olanzapine or placebo and were seen weekly for 16 weeks. The primary outcome measures were rate of change in body weight and rate of change in obsessionality, assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS). Seventy-five participants were assigned to receive olanzapine and 77 to receive placebo. A statistically significant treatment-by-time interaction was observed, indicating that the increase in BMI over time was greater in the olanzapine group (0.259 [SD=0.051] compared with 0.095 [SD=0.053] per month). There was no significant difference between treatment groups in change in the YBOCS obsessions subscale score over time (-0.325 compared with -0.017 points per month) and there were no significant differences between groups in the frequency of abnormalities on blood tests assessing potential metabolic disturbances. This study documented a modest therapeutic effect of olanzapine compared with placebo on weight in adult outpatients with anorexia nervosa, but no significant benefit for psychological symptoms. Nevertheless, the finding on weight is notable, as achieving change in weight is notoriously challenging in this disorder.

Comparing Risperidone and Olanzapine to Tetrabenazine for the Management of Chorea in Huntington Disease: An Analysis from the Enroll-HD Database.

Huntington's chorea (HC) is commonly managed with neuroleptic medications, though there is little evidence to support their use. This study aimed to perform a real-world comparison of the efficacy of risperidone and olanzapine to tetrabenazine (TBZ) for HC. The Enroll-HD database was used to perform a propensity score-matched comparison of risperidone and olanzapine to TBZ, regarding their efficacy in controlling chorea. Participants with motor manifest Huntington's disease (HD) were grouped according to their use of risperidone, olanzapine, or TBZ. For the three groups, independent propensity score matching was performed on participants' baseline total functional score (TFC), baseline total motor score (TMS), disease burden score, CAG repeat length, baseline age, region, sex, and body mass index. Independent samples t test was used to calculate the differences between the groups in the annual rate of change of the TMS from the baseline to the second available visit. The risperidone (n = 72) and olanzapine groups (n = 77) had annualized increases (worsening) in the TMS of only 1.47 points and 3.20 points, respectively, compared to 5.70 points in the two matched TBZ groups (n = 72) (P = 0.019) and (n = 77) (P = 0.143), respectively. In the absence of prospective data, this analysis of the Enroll-HD database found that the neuroleptics risperidone and olanzapine seemed to at least be comparable to TBZ at controlling HC. These results demonstrate that neuroleptics may have comparable efficacy to TBZ for the treatment of HC. Further prospective studies are needed to confirm these findings.

Clinical study on diazepam combined with olanzapine in treatment of agitation in alcohol withdrawal delirium tremors

Objective To compare the efficacy and safety of diazepam combined with olanzapine in treatment of agitation symptoms in patients with alcohol withdrawal delirium tremors(DT). Methods Totally 60 inpatients with DT according to CCMD-3 were enrolled in a 7-day, with 30 patients in the diazepam group (control group) and 30 patients in diazepam combined with olanzapine group (research group). The delirium rating scale(DRS-R-98) was used to evaluate the severity of the delirium symptoms. The positive and negative syndrome scale excited component(PANSS-EC) was used to assess the agitation symptoms.The treatment emergent symptom scale (TESS) was used to assess the safety and the vital signs. Results There was no significant difference in the delirium recovery time between the two groups(M(QR): 24 h(24 h)vs 24 h(6 h))(Z=-0.45, P=0.65). The PANSS-EC score in research group(17.00±2.67) was significant lower than that in control group(19.80±2.43) at the 6 hours after treatment(t=4.26, P 0.05). One case of dizziness, 2 cases of lethargy in the control group; 1 case of nasal congestion, 5 cases of drowsiness, 3 cases of constipation, 3 cases of dry mouth, 1 case of abnormal liver function in the research group. Conclusion The combination of olanzapine with diazepam can not reduce the recovery time of DT, but can quickly improve the agitation behavior. Key words: Delirium tremors; Agitation behavior; Diazepam; Olanzapine

Effects of ABCB1 gene polymorphisms on autonomic nervous system activity during atypical antipsychotic treatment in schizophrenia

BackgroundThere are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia.MethodsIn total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method.ResultsFor aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier–rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier–rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642–rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582).ConclusionWe suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

Safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms in dementia: a meta-analysis

Objective: To assess the safety of olanzapine, risperidone and quetiapine drugs in dementia patients with behavioral and psychological symptoms. Methods: The EMBASE, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews, Medline, CNKI, Wang Fang were systematically searched for eligible randomized controlled trials of olanzapine, risperidone and quetiapine drugs therapy in patients with psychotic symptoms of dementia before February 2016. Two reviewers independently assessed the quality of the trials and extracted information. All the data was analyzed with meta analysis and software of the Revman5.3 provided by Cochrane network. Results: Overall, 16 relevant RCTs with 1 727 participants were identified (olanzapine group: 672; quetiapine group: 395; risperidone group: 660). (1)Olanzapine group had higher incidence of somnolence than risperidone group (OR=1.49, 95% CI [-1.01-2.21], P=0.05), while for the dizziness, agitation, accidental injury, weight gain, abnormal gait, weakness, sleep disorders, extrapyramidal symptoms, there were no significant difference. (2) Risperidone had higher incidence of extrapyramidal symptoms than quetiapine group (OR=0.11, 95% CI [0.04-0.27], P=0.64), the incidence of somnolence was lower than quetiapine group (OR=0.03, 95% CI [1.06-3.51], P=0.03), while for accidental injury, dizziness, fatigue, insomnia, constipation, there were no significant difference. (3) Olanzapine group had higher incidence of extrapyramidal symptoms than quetiapine group (OR=11.10, 95% CI [3.35-36.75], P<0.000 1), while for somnolence, sleep disturbances, constipation, agitation, weight gain, dizziness, there was no significant difference. (4) The subgroup analysis showed that in the Chinese population, compared with the population in Europe and America, risperidone group had higher incidence of agitation, sleep disorders than olanzapine (agitation: [OR= 0.26, 95% CI [0.08-0.82]; sleep disorders: OR= 0.31, 95% CI [0.10-0.99]), olanzapine group had higher incidence of weight gain than quetiapine (OR=6.8, 95% CI [2.00-23.14]). Conclusions: Among olanzapine, risperidone and quetiapine, risperidone has lowest incidence of somnolence, quetiapine has lowest incidence of extrapyramidal symptoms. In the Chinese population, compared with the population in Europe and America, risperidone group has higher incidence of agitation, sleep disorders than olanzapine, and olanzapine group has higher incidence of weight gain than quetiapine.

Comparison of Olanzapine versus Other Second-Generation Antipsychotics in the Improvement of Insight and Medication Discontinuation Rate in Schizophrenia.

BackgroundIn the last decade, olanzapine became widely used in mental health service worldwide even after being criticized for its metabolic side effects. Patients with schizophrenia on olanzapine were usually found to stay on their medications longer than the other second-generation antipsychotics (SGAs) except clozapine. The reason for this is unknown.ObjectiveThis prospective study compared the influences of olanzapine and other SGAs except clozapine on improving insight and medication discontinuation rate in schizophrenia.MethodsA total of 148 patients with schizophrenia medically indicated for initiation of treatment with olanzapine or other SGAs were evaluated for symptoms, insight, attitudes toward medication, side effects, body weight and fasting lipid and glucose parameters at admission and before discharge, and follow-up calls one-year after discharge documented whether they were regularly taking prescribed psychotropic medication or not.ResultsAfter an average of 72.8 days of inpatient treatment, the olanzapine and other SGAs group exhibited similar levels of symptom improvement with an average reduction of 28.7 in the Positive and Negative Syndrome Scale (PANSS) total score. The Olanzapine group exhibited better improvement in insight assessed using the G12 item of PANSS and Insight and Treatment Attitudes Questionnaire (ITAQ), more metabolic side effects indexed with total cholesterol, triglycerides levels and weight gain, and a lower medication discontinuation rate than the other SGAs group.ConclusionAlthough general symptom improvement was similar, olanzapine significantly improved insight and presented less medication discontinuation compared to other SGAs, which might partially explain why patients on olanzapine stayed longer on their medications.

High-density lipoprotein-cholesterol and antipsychotic medication in overweight inpatients with schizophrenia: post-hoc analysis of a Japanese nationwide survey

BackgroundPatients with schizophrenia have an increased prevalence of metabolic disturbances compared with the general population. However, the mechanisms underlying the metabolic side effects of antipsychotics are unknown. The aim of the present study was to compare the levels of high-density lipoprotein (HDL)-cholesterol in Japanese schizophrenia patients medicated with olanzapine, risperidone, or aripiprazole monotherapy.MethodsThis study was a post-hoc analysis of a nationwide survey, which included 433 Japanese outpatients with schizophrenia and 674 inpatients. A brief questionnaire was compiled that covered demographic data, systolic blood pressure, diastolic blood pressure, and HDL-cholesterol after reviewing the relevant literature and guidelines. To compare demographic and clinical characteristics, analysis of variance was performed for continuous variables and the chi-square test was performed for categorical variables. For comparisons of HDL-cholesterol levels among the three antipsychotic groups, analysis of covariance was carried out with age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference as confounding variables after stratification by body mass index (BMI) for each outpatient group and inpatient group.ResultsThe mean age was 57.9 ± 14.0 years and the mean BMI was 23.4 ± 4.5 kg/m2. HDL-cholesterol levels when stratified by BMI differed significantly (p = 0.019) between the three antipsychotic groups after age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference in inpatients. A significant difference in HDL-cholesterol levels was only found in the overweight inpatient group, and no significant differences in HDL-cholesterol levels were found among the three antipsychotics for outpatients of all BMI stratifications or inpatients that were underweight or of normal weight. For post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group (p = 0.023).ConclusionsThis study reveals a difference in HDL-cholesterol levels in overweight Japanese inpatients with schizophrenia resulting from the use of different antipsychotics. In the post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group. Further studies incorporating more detailed evaluations, including diet and physical activity, are needed to clarify the differences in HDL-cholesterol according to antipsychotic use.

Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients.

This is the first study to identify lipidomic markers in plasma associated with response of acutely ill schizophrenia patients in response to specific antipsychotic treatments. The study population included 54 schizophrenia patients treated with antipsychotics for 6 weeks. Treatment led to significant improvement in positive and negative symptoms for 34 patients with little or no improvement for 20 patients. In addition, 37 patients showed an increase in body mass index after the 6 week treatment period, consistent with effects on metabolism and the association of such effects with symptom improvement. Profiling of plasma samples taken prior to therapy using liquid chromatography tandem mass spectrometry (LC-MS/MS) resulted in identification of 38, 10, and 52 compounds associated with the olanzapine, risperidone, and quetiapine treatment groups, which could be used to distinguish responders from non-responders. Limitations include the retroactive active nature of the study and the small sample size. Further investigations with larger sample sets could lead to the development of a molecular test that could be used to help psychiatrists determine the best treatment options for each patient.

Olanzapine as antiemetic drug in oncology: a retrospective study in non-responders to standard antiemetic therapy

Background The role of olanzapine in the treatment of chemotherapy-induced nausea and vomiting (CINV) in addition to the antiemetic therapeutic combination with aprepitant, setrons, and corticosteroids has not been well defined. Objective To investigate the effectiveness of the addition of olanzapine to a standard triplet therapy for the prevention of CINV in patients who experienced CINV during their first chemotherapy course, despite receiving a well-managed prevention protocol. Setting One comprehensive cancer centre in France. Method In a retrospective study with comparator, patients with a high risk of emesis were assigned to two groups during two different 6-month periods, before and after the introduction of olanzapine in clinical practice, respectively. In the olanzapine group, the antiemetic protocol for the second course of chemotherapy was reinforced by the addition of olanzapine at 5mg/day from day 1 to 5 in contrast with the control group. Main outcome measure The proportion of patients who experienced neither nausea nor emesis during the delayed phase (24-120h). Results The 25 patients in each group exhibited comparable characteristics and emetic chemotherapy level. During the first course, no significant difference was observed. During the second course, nausea and vomiting were ameliorated in 12 patients in the olanzapine group and 4 patients in the control group (p < 0.05). Nausea (12 vs. 4, p < 0.05) and vomiting (18 vs. 11, p < 0.05) also significantly improved. In the OLZ group, no adverse event was linked to olanzapine use. Conclusion The addition of olanzapine was observed to effectively restore CINV prevention in patients who did not respond to standard antiemetic therapy.

Long-term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL/6J mice.

Objective(s):Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet.Materials and Methods:Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured.Results:Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly.Conclusion:Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver.

F232. A PHASE 3 STUDY TO DETERMINE THE ANTIPSYCHOTIC EFFICACY AND SAFETY OF ALKS 3831 IN ADULT PATIENTS WITH ACUTE EXACERBATION OF SCHIZOPHRENIA

BackgroundALKS 3831, currently under development for the treatment of schizophrenia, is composed of a flexible dose of olanzapine (OLZ) and a fixed dose of 10 mg of samidorphan. In a Phase 2 study, ALKS 3831 mitigated OLZ-associated weight gain and exhibited antipsychotic efficacy similar to OLZ alone. This Phase 3 study assessed antipsychotic efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.MethodsThis was an international (USA, Ukraine, Serbia, and Bulgaria), 4-week, randomised, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomised 1:1:1 to receive either ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2 weeks of the study and could be treated as inpatients or outpatients for the remaining 2 weeks. Patients were excluded if they received OLZ within 6 months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S), and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).ResultsOf 401 patients randomised and dosed to ALKS 3831, OLZ, and PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831 and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body-mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean ± standard deviation scores were 101.7 ± 11.9 for PANSS total score and 5.1 ± 0.7 for CGI-S score. The mean OLZ dose was 18.4 mg/day in both active treatment arms. Least squares (LS) mean difference ± standard error (SE) versus PBO from baseline to Week 4 in PANSS total score was –6.4 ± 1.8 (P<.001) for the ALKS 3831 group and –5.3 ± 1.8 (P=.004) for the OLZ group. LS mean difference ± SE vs PBO from baseline to Week 4 in CGI-S score was −0.38 ± 0.12 (P=.002) for the ALKS 3831 group and −0.44 ± 0.12 (P<.001) for the OLZ group. The percentage of patients with an improvement in PANSS response (≥30% improvement from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5%) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.DiscussionALKS 3831 demonstrated greater antipsychotic efficacy than PBO, as measured by the PANSS and CGI-S scale, and was similar to the active control, OLZ. The safety profile of ALKS 3831 was similar to OLZ.

T5. LURASIDONE AND RISK FOR METABOLIC SYNDROME IN PATIENTS WITH SCHIZOPHRENIA: A COMPREHENSIVE DATABASE ANALYSIS

BackgroundPatients with schizophrenia are at increased risk for developing metabolic syndrome, with an estimated prevalence of approximately 35–50% (Correll et al. Psychiatr Serv 2010;61:892–98; Vancampfort et al. World Psychiatry 2015;14:339–47). Treatment with atypical antipsychotic medications have been shown to increase rates of metabolic syndrome, with differences observed among antipsychotic agents, most notably in propensity for weight gain: higher for olanzapine, clozapine, and iloperidone; intermediate for quetiapine, risperidone, and paliperidone; and lower for amisulpride, aripiprazole, asenapine, lurasidone, and ziprasidone (Leucht et al. Lancet 2013;382:951–62). Independent of weight gain, atypical antipsychotics also appear to have direct effects on lipid metabolism and glucose regulation. The aim of this safety analysis was to assess the effects of treatment with lurasidone on metabolic syndrome risk in patients with schizophrenia.MethodsChanges in the rate of metabolic syndrome during treatment with lurasidone (40–160 mg/d) versus active comparators (olanzapine, quetiapine, risperidone) were analyzed using pooled short-term data from 3 randomized, double-blind, placebo-controlled studies; long-term data from 2 active-controlled studies; and switch data from 2 open-label extension studies. Metabolic syndrome was defined based on the National Cholesterol Education Program criteria (NCEP ATP III; 2005 revision).ResultsIn short-term studies, risk of treatment-emergent metabolic syndrome was similar for patients in the lurasidone and placebo groups (odds ratio [OR]=0.97; week 6 LOCF-endpoint); and was significantly greater for patients in the olanzapine (OR=2.68; P<0.001) and quetiapine (OR=3.70; P<0.001) groups compared to placebo. In long-term studies, risk of treatment-emergent metabolic syndrome after 12 months was significantly lower for lurasidone compared with risperidone (OR=0.374; 95% CI, 0.180–0.774; P<0.01) and non-significantly lower for lurasidone compared with quetiapine XR (OR=0.267; 95% CI, 0.040–1.806; P>0.05). In open-label switch studies, the rate of metabolic syndrome decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone.DiscussionIn this comprehensive analysis of the lurasidone clinical trial data base, treatment with lurasidone (40–160 mg/d) was not associated with the development of metabolic syndrome in patients with schizophrenia. Rates of metabolic syndrome increased in patients treated with olanzapine, risperidone, and quetiapine XR.

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy: Results of the Korean South West Oncology Group (KSWOG) Study.

PurposeData on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC.Materials and MethodsWe conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL.ResultsFifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015).ConclusionOlanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

Comparison of social function, adverse reaction and medication adherence of Paliperidone, Amisulpride and Olanzapine in patients with first-episode schizophrenia

Objective To investigate the social function, adverse reaction and medication adherence of paliperidone, amisulpride, and olanzapine in patients with first episode schizophrenia. Methods A total of 96 patients with first episode of schizophrenia was randomly divided into three groups, with reference to random numbers, among which there were 32 in paliperidone group, 32 cases in amisulpride group, and 32 in olanzapine group. All the patients in all groups were assessed with negative and positive scale (PANSS), personal and social performance scale (PSP), drug attitude inventory (DAI) at baseline and the end of 6 months. Results ⑴ There was no significant difference in the therapeutic effect between three groups (P>0.05); ⑵ The scores of PSP and DAI were increased in three groups after treatment, and the difference was statistically significant compared to that before treatment (P<0.05). Conclusions Three drugs have similar efficacy in the treatment of first-episode schizophrenia, and there is no significant difference in improving medication compliance and social function. Key words: Antipsychotic agents/TU; Isoxazoles/AA; Isoxazoles/TU; Benzodiazepines/TU; Schizophrenia/DT; Treatment outcome

Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

Background:This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs).Methods:The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded.Results:Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference.Conclusion:Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

Contribution of parasympathetic muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia.

Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet- and activity-controlled inpatient conditions. Before and after 7 days of study drug administration, subjects underwent frequently sampled intravenous glucose tolerance tests with either saline or atropine infused on subsequent days to assess insulin secretion and hepatic insulin extraction in the absence or presence of muscarinic blockade. We found that olanzapine led to an increase in the acute insulin response to glucose, which was not seen with placebo, and was attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data confirmed an increase in insulin secretion with olanzapine, which was blocked by atropine, with a modest reduction in hepatic insulin extraction with olanzapine. These results support the contribution of muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the compensatory hyperinsulinemia that normally serves to prevent deterioration of glucose tolerance under conditions of metabolic challenge.

Effects of different antipsychotics on sugar, lipid metabolism and body mass in female patients with first-episode schizophrenia

Objective To study the effects of atypical antipsychotic drugs on glucose and lipid metabolism and body weight in female patients with schizophrenia. Methods 120 patients with schizophrenia were randomly divided into three groups according to the number randomized method.Group 1(olanzapine group) was treated with olanzapine, group 2(ziprasidone group) was treated with ziprasidone, group 3(risperidone group) was treated with risperidone.The total cholesterol (TC), triglyceride (TG) and body mass index (BMI) in the three groups were analyzed retrospectively. Results After treatment for 8 weeks, the fasting blood glucose of the olanzapine group and risperidone group increased significantly compared with before treatment, the differences were statistically significant(t=-2.81, P 0.05). After treatment for 8 weeks, the BMI of the olanzapine group and risperidone group had statistically significant difference compared with before treatment(t=-3.62, P 0.05). After treatment for 8 weeks, the TG, TC levels of the olanzapine group had statistically significant differences compared with before treatment (t=-3.89, P 0.05; t=-1.06, P>0.05; t=-0.55, P>0.05; t=-0.62, P>0.05). Conclusion Ziprasidone in the treatment of female first episode schizophrenia, has less influence on sugar, lipid metabolism and weight, with high compliance and more advantages compared with other atypical antipsychotics. Key words: Schizophrenia; Antipsychotics agents; Metabolism; Body weight; Female