Improved outcomes following a switch to olanzapine treatment from risperidone treatment in a 1-year naturalistic study of schizophrenia patients in Japan

Aims: This study assessed clinical and functional outcomes following a switch from risperidone to olanzapine in a 1‐year naturalistic study of schizophrenia patients in Japan. Methods: We used data from a large 1‐year prospective, multicenter, observational non‐interventional study of individuals who were initiated on olanzapine for the treatment of schizophrenia in Japan. Current analyses focused on patients who were switched at study entry from risperidone to olanzapine (n = 258). Repeated measures analysis was employed to assess outcomes on validated measures. Results: At study entry, 45% were inpatients and 55% outpatients. Participants were in their early 40s with mean illness duration of 14 years. Approximately half were male. Most were switched from risperidone to olanzapine due to poor medication efficacy (67.8%) rather than medication intolerability (29.1%). Most patients (67.8%) completed the 1‐year study. Patients experienced clinically and statistically significant (P < 0.05) improvements in global symptom severity, positive, negative, depressive, and cognitive symptoms, health‐related quality of life, and paid work rates. Most patients (59.2%) demonstrated treatment response to olanzapine and 43.4% experienced symptom remission. Mean weight gain was 2.19 kg, with one‐third of patients (33.3%) experiencing clinically significant weight gain (≥7%). Conclusions: In this 1‐year naturalistic study, inpatients and outpatients who were switched from risperidone to olanzapine experienced clinically and statistically significant improvements in their clinical and functional outcomes. One‐third of all patients experienced clinically significant weight gain. Current findings highlight the favorable benefit‐to‐risk profile of switching to olanzapine therapy following treatment failure on risperidone among patients with schizophrenia in Japan.     

Comparative effectiveness of second-generation antipsychotic medications in early-onset schizophrenia

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.     

Olanzapine vs. risperidone in patients with first-episode schizophrenia and a lifetime history of cannabis use disorders: 16-week clinical and substance use outcomes

The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n = 28) or risperidone (n = 21) for 16 weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and the Scale for Assessment of Negative Symptoms (SANS) global asociality-anhedonia scores improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within three months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse.     

利培酮与奥氮平治疗首发精神分裂症的1年随访研究

目的评价利培酮与奥氮平治疗首发精神分裂症的疗效与不良反应。方法本研究为开放性，平行对照，药物剂量可调整的临床试验。采用自然观察研究方法，结合全病程管理模式对研究对象进行1年随访研究。分别有131例和136例首发精神分裂症患者被分入利培酮组和奥氮平组。利培酮组剂量为3—6mg，平均（3．8±1．3）mg，奥氮平组剂量为10—20mg，平均（12．9±5．6）mg。疗效主要统计指标为阳性和阴性症状评定量表（PANSS）的总分值及有效率，持续治疗时间。PANSS减分率≥50％定义为有效。次要统计指标为复发率、复发时间及药物不良反应。用副反应量表（TESS）评估药物不良反应。结果12月末时，利培酮组有85例患者（64．9％）完成随访，奥氮平组为93例（68．4％），两组差异无统计学意义（P〉0．05）。治疗终点利醅酮和奥氮平组有效率分别为62．6％和69．8％，差异无统计学意义（P〉0．05），随访中其他时点（2、3、6、8个月）两组有效率差异亦无统计学意义。12个月末利培酮组和奥氮平组的复发率（14．5％、12．5％）、持续治疗时间（9．5±3．8月、9．7±3．8月）、复发时间（4．0±2．9月、5．1±2．8月）等差异均无统计学意义（均P〉0．05）。不良反应方面，利培酮组锥体外系反应比例高于奥氮平组，奥氮平组体重增加比例高于利培酮组。结论利培酮与奥氮平治疗首发精神分裂症1年疗效均好，利培酮组锥体外系反应发生较多，奥氮平组体重增加较多。     

Probiotics Plus Dietary Fiber Supplements Attenuate Olanzapine-Induced Weight Gain in Drug-Naïve First-Episode Schizophrenia Patients: Two Randomized Clinical Trials

Background and HypothesisAntipsychotic-induced weight gain is associated with alterations to the composition of the gut microbiota. The purpose of this study was to determine the effect of probiotics plus dietary fiber on antipsychotic-induced weight gain.Study DesignTwo sequential, randomized clinical trials were conducted. In Study 1, 90 drug-naïve, first-episode schizophrenia patients were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy for 12 weeks. In Study 2, 60 drug-naïve, first-episode schizophrenia patients were randomly assigned to receive either olanzapine plus probiotics and dietary fiber or olanzapine monotherapy for 12 weeks.Study ResultsIn Study 1, no significant differences in weight gain were observed between the two groups. The insulin resistance index (IRI) was lower in the olanzapine plus probiotics group compared with the olanzapine monotherapy group at week 12 (estimated mean difference, −0.65, [95% confidence interval (CI), −1.10 to −0.20]; p = .005). In Study 2, weight gain was lower in the probiotics plus dietary fiber group than in the olanzapine monotherapy group at week 12 (estimated mean difference −3.45 kg, [95% CI, −5.91 to −1.00]; p = .007). At week 12, IRI increased significantly in the olanzapine monotherapy group (mean, 1.74; standard deviation (SD) = 1.11, p < .001), but not in the olanzapine plus probiotics and dietary fiber group (mean 0.47, SD = 2.16, p = .35) with an estimated mean difference of −0.95 between the two groups [95% CI, −1.77 to −0.14]; p = .022).ConclusionsThese results provide support for the efficacy and safety of probiotics plus dietary fiber in attenuating antipsychotic-induced weight gain in drug-naïve, first-episode schizophrenia patients.     

Weight gain in patients with schizophrenia treated with risperidone,olanzapine, quetiapine or haloperidol: results of the EIRE study

OBJECTIVES: The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain. METHOD: Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments. RESULTS: Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>or=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>or=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with 相似文献   

Quality of life in schizophrenia: a multicenter, randomized, naturalistic, controlled trial comparing olanzapine to first-generation antipsychotics

OBJECTIVE: To assess the effectiveness of olanzapine for treating schizophrenia and to assess if olanzapine promotes a better quality of life than first-generation antipsychotics (FGAs). METHOD: Multicenter, naturalistic, randomized controlled study, comparing olanzapine with FGAs, at hospitalization and during a 9-month follow-up. Outcome assessors were blind to the allocated drug. The dose of antipsychotic was determined by doctors according to their clinical practice routines. Data collection was performed from April 1999 to August 2001. RESULTS: 197 patients with DSM-IV-diagnosed schizophrenia were allocated to olanzapine (N = 104) and FGA (N = 93). Patients taking olanzapine showed greater improvements in Positive and Negative Syndrome Scale (PANSS) negative symptoms (mean difference = 2.3, 95% CI = 0.6 to 4.1) and general psychopathology (mean difference = 4.0, 95% CI = 0.8 to 7.2) sub-scales and fewer incidences of tardive dyskinesia (RR = 2.4, 95% CI = 1.4 to 4.2, p < .0001). Olanzapine was also associated with greater improvement in a number of health-related quality-of-life outcomes on the Medical Outcomes Study 36-item Short-Form Health Survey, including physical functioning (mean difference = 6.6, 95% CI = 1.2 to 11.9), physical role limitations (mean difference = 13.7, 95% CI = 3.0 to 24.3), and emotional role limitations (mean difference = 12.1, 95% CI = 0.7 to 23.5). Patients taking olanzapine gained significantly more weight during the trial than patients taking FGAs, with a correspondent endpoint increase in the body mass index (BMI) of 28.7 versus 25.3 (p < .001). CONCLUSION: Compared with FGAs, olanzapine has advantages in terms of improvements of negative symptoms and quality of life. It is also associated with fewer incidences of tardive dyskinesia and greater increases in weight and BMI. These findings are highlighted by the naturalistic approach adopted in this trial.     

Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized,double-blind trial of olanzapine versus haloperidol

OBJECTIVE: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. METHOD: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. RESULTS: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). CONCLUSIONS: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.     

New-onset type-2 diabetes associated with atypical antipsychotic medications

PURPOSE: This study compared the one-year incidence of new-onset type-2 diabetes mellitus (DM) and changes in weight in patients with a variety of psychiatric diagnoses prescribed olanzapine, risperidone, or quetiapine, compared to a reference group receiving haloperidol and no other antipsychotic medication. RESEARCH DESIGN AND METHODS: Data was abstracted from charts of subjects newly initiated and then maintained for one year on olanzapine (n=112), risperidone (n=100), quetiapine (n=100), and haloperidol (n=100). Baseline and one-year DM status, height, and weight were collected, as well as concurrent psychotropic medications, medical and psychiatric comorbidities. FINDINGS: Using a multivariate model, logistic regression identified a significant association between olanzapine (but not other atypical agents) and the development of diabetes compared to haloperidol over the one-year period (odds ratio 8.4, 95% CI 1.8-38.7). Baseline obesity was independently associated with new-onset DM, but only marginally greater weight gain was found among olanzapine users. CONCLUSIONS: The middle-aged American veterans in this study cohort were highly vulnerable to the diabetogenic effects of olanzapine, but a close correlation with weight change was not found. Patients administered olanzapine should receive careful laboratory monitoring for elevated plasma glucose in addition to weight measurement.     

Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia

OBJECTIVE: To examine clinical outcomes in Asian patients with schizophrenia receiving monotherapy with olanzapine, risperidone or typical antipsychotics in naturalistic settings. METHOD: In this report, data from the first 12 months of the prospective, observational, 3-year Intercontinental Schizophrenia Outpatient Health Outcomes study are presented for patients from participating Asian countries (Korea, Taiwan and Malaysia) who were started on, or switched to, monotherapy with olanzapine (n = 484), risperidone (n = 287) or a typical antipsychotic drug (n = 127) at baseline. RESULTS: At 12 months, overall reduction in the score of Clinical Global Impressions-Severity of Illness rating scale was greatest with olanzapine (p < 0.001 vs typical agents), followed by risperidone (p = 0.007 vs typical agents) treatment. Olanzapine treatment was found to have significantly better effects than typical agents on negative and depressive symptom scores, and significantly greater improvements than risperidone on negative and cognitive symptoms. The occurrence of extrapyramidal symptoms was least likely with olanzapine (p < 0.001 vs typical agents, and p = 0.012 vs risperidone), while the estimated odds of tardive dyskinesia were greatest in the typical treatment group (p = 0.046 vs olanzapine, and p = 0.082 vs risperidone). Mean weight increase was greater for olanzapine-treated patients compared with the other agents (p = 0.030 vs typical agents and p < 0.001 vs risperidone). The risk of menstrual disturbance was relatively high with risperidone when compared with olanzapine treatment (p < 0.001). CONCLUSIONS: The results of this observational study indicate that, in Asian patients with schizophrenia, olanzapine may offer benefits when compared with typical agents or risperidone. However, the significantly greater odds of weight gain should be considered in the clinical management of olanzapine-treated patients.     

利培酮、奥氮平和喹硫平治疗未服药的精神分裂症患者的疗效和不良反应：1年自然观察研究

背景第二代抗精神病药被日益广泛地用于治疗精神分裂症首次发作,但其疗效是否一致尚有争议。假设利培酮、奥氮平、喹硫平治疗未服药的首次发病的精神分裂症或分裂样精神障碍患者,其1年的疗效是一致的。方法采用自然观察研究方法,对病程≤5年,符合ICD-10精神分裂症或分裂样精神障碍研究用诊断标准的未服药门诊患者随访1年。纳入398例患者,分别用利培酮（131例）、奥氮平（136例）、喹硫平（131例）单药治疗。在开始治疗后的第2周,2、3、6、8以及12个月时采用阳性与阴性综合征量表（Positive and Negative Syndrome Scale,PANSS）评估疗效,用副反应量表（Treatment Emergent Symptom Scale,TESS）评估治疗中出现的不良反应,非盲法评定。结果共269例（67%）患者完成1年随访。利培酮组、奥氮平组和喹硫平组的停药率分别为35.1%（46/131）、31.6%（43/136）和32.1%（42/131）,χ^2=0.43,P=0.809。对脱落患者的资料采用末次观察结转法,1年时利培酮组、奥氮平组和喹硫平组的PANSS总分平均值（标准差）分别减少46.8%（17.0%）,48.6%（19.6%）和47.3%（16.2%）,F=0.38,P=0.688。重复测量的方差分析显示,无论是PANSS总分还是分量表分,治疗各时点三组间差异均无统计学意义。治疗第2周时利培酮组发生震颤和静坐不能的比例高于其他两组。1年时,3组中常见的不良反应是体重增加和嗜睡,奥氮平组体重增加的比例（69.9%）高于其他两组。根据持续存在不良反应症状的时点数与总随访时点数的比值衡量不良反应的持续时间,锥体外系症状在利培酮组最明显,体重增加在奥氮平组最明显,心动过速在喹硫平组最明显。结论利培酮、奥氮平、喹硫平单药治疗未服药的精神分裂症或分裂样精神障碍患者1年疗效相似,但不良反应有所不同。     

Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study

OBJECTIVE: To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD: The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS: The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS: Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk.     

Risk of weight gain associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain occurs in a substantial percentage of treated persons. There remains a paucity of naturalistic data that describe relative weight-gain liability with the available novel atypical antipsychotics (NAPs). This investigation describes comparative NAP-induced weight gain in a prospective naturalistic cohort of persons with schizophrenia and related psychotic disorders. METHODS: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is an ongoing prospective, longitudinal, naturalistic study involving 32 academic and community sites across Canada. Persons with DSM-IV-defined schizophrenia, schizophreniform or schizoaffective disorder, and psychosis not otherwise specified were consecutively enrolled. The overarching objectives of this initiative were to collect and compare global effectiveness, tolerability, safety, and humanistic outcomes in persons receiving commercially available NAPs in Canada. This analysis reports only weight change with the respective NAPs. Other outcomes were reported in separate companion papers. RESULTS: A spectrum of weight-gain liability was noted with quetiapine (QUE) (mean 7.55 kg, SD 9.20; P = 0.28), olanzapine (OLZ) (mean 3.72 kg, SD 0.56; P = 0.15), and risperidone (RIS) (mean 1.62 kg, SD 7.72; P = 0.43). Categorically defined weight gain (that is, over 7% of baseline weight) was observed in 55.6% of QUE patients, 24.1% of OLZ patients, and 23.7% of RIS patients. Adjusting for demographic and disease-specific confounding factors, QUE patients had greater odds of gaining over 7% of their baseline weight compared with RIS patients (odds ratio [OR] 3.62; 95% CI, 1.02 to 12.83; P = 0.05). No statistical difference was detected between OLZ patients and RIS patients for over 7% of baseline weight (OR 1.54; 95% CI, 0.63 to 3.75; P = 0.12) or over 10% weight gain (OR 1.44; 95% CI, 0.50 to 4.13; P = 0.58). CONCLUSION: Clinicians are reminded to monitor anthropometric and metabolic parameters in all NAP-treated persons. Clinically significant differences in weight gain liability exist among the available NAPs.     

Long-term observational comparison of risperidone and olanzapine in bipolar disorder.

To compare long-term effectiveness and safety of risperidone versus olanzapine as adjunctive maintenance treatments of bipolar disorder. Retrospective observational chart review of 29 outpatients with bipolar or schizoaffective disorder (type I = 15, type II = 3, NOS = 5, schizoaffective = 6) who received risperidone or olanzapine added to lithium or valproate >3 months. Acute indications were depression (n = 8), manic/hypomanic/mixed states (n = 8), rapid cycling (n = 6), other indications (n = 6), and prophylaxis (n = 1). Logistic regression models adjusted for potential confounding factors (i.e., severity of illness, comorbid substance abuse, diagnostic subtype). Overall duration of follow-up was 65.9+/-70.1 weeks. Mild to moderate response was similar in the risperidone and olanzapine groups after adjusting for potential confounders (OR = 0.91, 95% CI [0.05, 16.17]). Somewhat greater adjusted moderate to marked response (OR >3.60, 95% CI [0.31, >42.00]) and longer duration of treatment (HR = 0.52, 95% CI [0.22, 1.22]) occurred in the risperidone group, but were still compatible with the null hypothesis. Weight gain occurred more frequently with olanzapine (57%) than risperidone (13%). EPS was similar, and tardive dyskinesia did not occur. Risperidone and olanzapine appeared to have similar real-world maintenance effectiveness for bipolar disorder, but differed somewhat in side effects.     

Safety,effectiveness, and quality of life of olanzapine in first-episode schizophrenia: a naturalistic study

OBJECTIVE: This study evaluated the effectiveness, safety, and quality of life (Qol) offered by olanzapine in first-episode schizophrenia. METHOD: One hundred and eighty-two patients with first-episode schizophrenia (ICD-10) drawn from a larger, naturalistic, study were evaluated after 6 months of treatment with olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was assessed using the Clinical Global Impression-Severity (CGI-S) and Global Assessment of Function (GAF). AWAD and EuroQol scales were used to evaluate patients' attitude towards medication and Qol, respectively. RESULTS: Subjects treated with olanzapine, risperidone, and CA showed similar improvements on CGI-S and GAF. Treatment-emergent, extrapyramidal symptoms were significantly lower in olanzapine-treated patients (17.8%) than in the risperidone (46.4%) and CA (62.2%) groups. Compared to CA, olanzapine and risperidone showed significantly greater improvement on the visual analog scale of EuroQol. Olanzapine-treated patients also showed significantly improved AWAD scores. CONCLUSIONS: In first-episode schizophrenia, atypical antipsychotics were effective, and improved Qol. Olanzapine had a lower incidence of extrapyramidal symptoms and better subjective acceptance of medication.     

Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone

OBJECTIVE: Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. METHOD: Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. RESULTS: In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. CONCLUSION: This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain.     

Atypical antipsychotics and risk of cerebrovascular accidents

OBJECTIVE: Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly. METHOD: The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts-users of typical antipsychotics, risperidone, and olanzapine-were identified and compared. RESULTS: Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4 (95% CI=0.7-2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.     

Antipsychotic treatment discontinuation in previously untreated patients with schizophrenia: 36-month results from the SOHO study

Data from the 3-year, prospective, observational SOHO study were used to compare the effectiveness (in terms of treatment discontinuation) and the tolerability of olanzapine, risperidone, other atypicals and typical antipsychotics in 1009 previously untreated outpatients with schizophrenia who started monotherapy at baseline. Kaplan-Meier survival analysis estimated the time to treatment discontinuation by the treatment group, Cox proportional hazards regression models identified the variables associated with treatment discontinuation (adjusted for baseline differences between treatment groups), and logistic regression models compared the tolerability profiles of the different treatment groups. Of the 931 patients analyzed, 31.9% discontinued the medication initiated at baseline during the 3-year follow-up. Olanzapine had the lowest rate of discontinuation (28.9%), followed by other atypical (34.0%), risperidone (36.2%) and typical antipsychotics (44.5%). Compared to olanzapine, risk of treatment discontinuation was higher with typical antipsychotics (hazard ratio [HR] 1.75; 95% confidence interval [CI] 1.11, 2.78) or risperidone (HR 1.36; 95% CI 1.02, 1.82). A higher baseline Clinical Global Impression (CGI) positive score was associated with a higher risk of treatment discontinuation (HR 1.18; 95% CI 1.06, 1.30). Olanzapine was associated with a lower frequency of extrapyramidal symptoms than other antipsychotics, fewer prolactin-related adverse events than risperidone and other atypical antipsychotics, but greater weight gain than typicals and risperidone. For all analyses, comparison with the other atypical group is limited due to its small sample size (n = 50). In conclusion, treatment effectiveness and tolerability varied among antipsychotic medications in previously untreated patients with schizophrenia. The results should be interpreted conservatively given the observational study design.     

Atypical antipsychotics and weight gain in Chinese patients: a comparison of olanzapine and risperidone

OBJECTIVE: To compare the effect of olanzapine with that of risperidone on weight change among Chinese patients in Hong Kong. METHOD: The body weight of subjects maintained on olanzapine or risperidone treatment was recorded at the outpatient clinic of a teaching hospital. Pretreatment weight of the subjects was retrieved from case records. Subjects on olanzapine treatment were matched in sex, age, and diagnosis with those on risperidone treatment, and demographic and clinical data were analyzed. The study was conducted in May and June 2002. RESULTS: Twenty-eight olanzapine-risperidone matched pairs were studied. All were diagnosed with DSM-IV schizophrenia. In patients treated with olanzapine and risperidone, respectively, mean +/- SD duration of treatment with atypical neuroleptics was 103.5 +/- 47.4 weeks and 93.2 +/- 50.6 weeks (range, 21-255 weeks), and mean doses were 12.4 +/- 6.7 mg/day and 4.5 +/- 2.8 mg/day. The mean +/- SD weight gain of subjects on treatment with olanzapine and risperidone, respectively, was 8.34 +/- 5.97 kg (18.53 +/- 13.27 lb) and 2.74 +/- 8.09 kg (6.09 +/- 17.98 lb) with a statistically significant difference at p < .005. Lower baseline body weight and body mass index were associated with greater weight gain in both olanzapine- and risperidone-treated subjects. Gender, age, mean daily dose, and duration of treatment had no effect on weight change. CONCLUSION: Treatment with olanzapine was associated with significantly greater weight gain than treatment with risperidone in Chinese schizophrenia patients in Hong Kong. The effect of adjunctive anticonvulsant treatment on weight gain requires further study.     

Risperidone versus olanzapine among patients with schizophrenia participating in supported employment: Eighteen-month outcomes

This study compares the efficacy and tolerability of olanzapine versus risperidone among patients with schizophrenia who are established in outpatient psychiatric care and entering supported employment. A multicenter, randomized, double-blind trial was conducted among 107 outpatients with schizophrenia, who were cross-titrated to flexible dose risperidone or olanzapine over 2 weeks. Clinical endpoints included time to hospitalization and persistence on assigned medication. Weight, laboratory tests, psychopathology, neurologic side effects, social adjustment and role functioning were assessed at 3–6 month intervals. Data were analyzed first by randomized treatment, and then reassessed controlling for prior medication treatment. The proportion of patients on assigned medication at 18 months was 30.9% for risperidone and 37.3% for olanzapine. Mean doses were 6.4 ± 3.2 mg daily for risperidone, and 17.0 ± 5.0 mg daily for olanzapine. The groups did not differ significantly in time to medication discontinuation, first hospitalization or first employment. There were few differences in psychopathology, laboratory, or neurological assessments between groups at 18 months. Patients randomized to olanzapine gained modestly more weight. Controlling for pre-randomization medication suggested improvement in some aspects of psychopathology from switching medications; however, switching from olanzapine to risperidone was associated with more hospitalizations. Risperidone and olanzapine have similar efficacy and tolerability in patients with schizophrenia who are participating in supported employment. Randomization to olanzapine was associated with more weight gain, but randomization from olanzapine to risperidone appeared to be associated with a greater likelihood of hospitalization. Careful monitoring of metabolic effects and participation in supported employment may have contributed to minimal weight gain and metabolic effects.