Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months. A double-blind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse. Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study. The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report. Olanzapine versus haloperidol in the treatment of patients with chronic schizophrenia: results of the Japan multicenter, double-blind olanzapine trial. Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression. Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia. Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia. Olanzapine in the treatment of schizophrenia : an open label comparative clinical trial from north India. A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia. The effect of famotidine addition on olanzapine-induced weight gain in first-episode schizophrenia patients: a double-blind placebo-controlled pilot study. The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophrenia. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia. Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.
Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.
                The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.
                In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).
                Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.
                Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities. 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.
                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.
                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%).
                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. The present study evaluated the effectiveness and safety of clozapine versus "high-dose" olanzapine in treatment-refractory adolescents with schizophrenia.
                Children, ages 10-18 years, who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were randomized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine (n = 18) or "high-dose" olanzapine (up to 30 mg/day) (n = 21). The primary efficacy measure was response (improvement), defined as a decrease of 30% or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of "1" (very much improved) or "2" (much improved).
                Significantly more clozapine-treated adolescents met response criteria (66%) compared with olanzapine-treated subjects (33%). Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point. However, both treatments were associated with significant weight-gain and related metabolic abnormalities.
                This double-blind randomized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice. The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments. To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.
                A multinational, double-blind randomised clinical trial.
                Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d).
                Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.
                Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 +/- 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 +/- 3.2 kg, p < 0.0001).
                Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight. Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders. Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate. This study, using placebo as a control, evaluated olanzapine's efficacy in preventing a psychotic relapse. Participants were stable minimally symptomatic outpatients with schizophrenia or schizoaffective disorder. The study included 4 phases: (1) 4-day to 9-day screening/evaluation (N = 583), (2) 6-week conversion to open-label olanzapine (N = 493; 10-20 mg/d), (3) 8-week stabilization on olanzapine (N = 458; 10-20 mg/d), and (4) 52-week randomized (2:1), double-blind maintenance with olanzapine (N = 224; 10-20 mg/d) or placebo (N = 102). Primary relapse criteria were clinically significant changes in the Brief Psychiatric Rating Scale (BPRS) positive item cluster or rehospitalization due to positive symptoms. Statistical methodology allowed sequential real-time estimation of efficacy across blinded treatment groups and multiple interim analyses, which permitted study termination when efficacy was significantly different between treatments. A significant between-treatment difference emerged 210 days after first patient randomization to double-blind treatment. Thus, 151 (46.3%) of the randomized patients were discontinued early and 34 (10.4%) of the planned patient enrollment were not required. The olanzapine group had a significantly longer time to relapse (P < 0.0001) than the placebo group. The 6-month cumulative estimated relapse rate (Kaplan-Meier) was 5.5% for olanzapine-treated patients versus 55.2% for placebo-treated patients. The design of this study enabled appropriate statistical testing of the primary hypothesis while minimizing exposure of patients to a less effective treatment than olanzapine. In remitted stabilized patients with schizophrenia or schizoaffective disorder, olanzapine demonstrated a positive benefit-to-risk profile in relapse prevention. The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents. Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies.
                Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings.
                Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group.
                This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes. This randomized double-blind trial was conducted to test the efficacy and safety of olanzapine in Japanese patients with schizophrenia. Importantly, this study also represents the first large clinical trial of olanzapine conducted in an Asian population. Patients (n = 182) were randomly assigned to treatment with olanzapine or haloperidol over a period of 8 weeks. The primary analyses included: (i) a test of non-inferiority of olanzapine compared with haloperidol in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison between the treatment groups in extrapyramidal symptom severity using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to haloperidol in efficacy in treating positive symptoms and significantly superior in treating negative symptoms. Extrapyramidal symptom severity was significantly improved for olanzapine-treated patients versus haloperidol-treated patients. Olanzapine was shown to be more effective and better tolerated than haloperidol in the treatment of Japanese patients suffering from chronic schizophrenia. A 6-week acute phase of an international 1-year double-blind study was conducted comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day, and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with schizophrenia. The purpose was to determine whether olanzapine demonstrated a dose-related ability to decrease overall psychopathology with minimal associated extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine group showed statistically significantly greater improvement in overall psychopathology based on mean change in the CGI Severity score and statistically significantly greater improvement in positive psychotic symptoms based on mean change in both the BPRS positive score and the PANSS positive score compared with the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose-response curve was observed across the range of all olanzapine dose groups. Acute extrapyramidal syndromes were reported less frequently among all olanzapine groups compared with the haloperidol group. Endpoint mean change on both the Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all olanzapine treatment groups compared with worsening for the haloperidol group. Olanzapine was associated with weight gain but did not appear to have any clinically meaningful effect on vital signs. Although olanzapine was associated with some increase in prolactin concentrations, increases were transient, occurred less often, and were of lesser magnitude than those observed with haloperidol. Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia. To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.
                Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.
                The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered "much" or "very much" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.
                Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects . Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.
                To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.
                Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.
                National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.
                Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.
                After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).
                The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.
                Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).
                While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events. Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.
                To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.
                Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).
                Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).
                Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.
                Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications. Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine.
                First-episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15).
                The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains.
                These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain. This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia.
                This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores.
                During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24).
                A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted. When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.
                Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).
                Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.
                For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects. The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia.
                In an 8-week, international, double-blind study, patients (outpatients, hospital inpatients, and residents of nursing or boarding homes) were randomly assigned to receive risperidone (1 mg to 3 mg/day) or olanzapine (5 mg to 20 mg/day). The main outcome measures were changes in Positive and Negative Syndrome Scale (PANSS) total scores and rates of extrapyramidal symptoms (EPS).
                Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder. The mean duration of illness was 36.5 years. Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine. PANSS total scores and four of the five PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, and anxiety/depression) improved significantly at all time-points and at endpoint in both groups; between-treatment differences were not significant. EPS-related adverse events were reported by 9.2% of patients in the risperidone group and 15.9% in the olanzapine group; the between-treatment difference was not significant. Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint; between-treatment differences were not significant. Clinically relevant weight gain was seen in both groups, but was significantly less frequent in risperidone patients than in olanzapine patients.
                Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms, with a relatively low risk of side effects. Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine. The aim of the present study was to assess the efficacy and safety of olanzapine in the treatment of schizophrenic patients. 27 patients were randomly assigned to treatment with olanzapine or haloperidol over 12 weeks. The primary efficacy measure was the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS) and assessing treatment emergent adverse events. Secondary measures were positive symptoms, negative symptoms, general psychopathology depression, anxiety and quality of life. Compared to haloperidol, olanzapine had equal effect in improving overall psychopathology, positive symptoms, and severity of schizophrenic illness. Olanzapine showed supehor improvement on negative symptoms and secondary depressive features. Commonest side effects were weight gain, sleepiness and increased duration of sleep. Olanzapine is effective in improving overall psychopathology including positive symptoms, negative and secondary depressive features in Indian patients with schizophrenia and it is safe and well tolerated at dosage between 5 to 20 mg/day. Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed. Olanzapine treatment is associated with substantial weight gain. In this double-blind placebo-controlled study we evaluated whether the H2 antagonist famotidine may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM-IV schizophrenia patients were randomly allocated to receive either famotidine (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6 weeks. All patients completed the trial. Patients in both groups showed a similar increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of 0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of their initial body weight, a cut-off for clinically significant weight gain. Famotidine addition was safe and well tolerated and did not interfere with olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6 weeks) is not effective in preventing/attenuating weight gain in olanzapine-treated first-episode schizophrenia patients. Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.
                To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.
                Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.
                66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.
                After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.
                Copyright 2003 John Wiley & Sons, Ltd. Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.
                Copyright 2006 John Wiley & Sons, Ltd. This international, multicenter double-blind trial was designed to compare the therapeutic profile of an atypical antipsychotic, olanzapine, with that of a conventional dopamine D2 antagonist, haloperidol.
                A total of 1,996 patients at 174 sites in Europe and North America were randomly assigned to treatment with olanzapine (N = 1,336) or haloperidol (N = 660) over 6 weeks. The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS). Secondary analyses included comparisons of the mean change in positive and negative symptoms, comorbid depression, extrapyramidal symptoms, and overall drug safety.
                Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure, including depression. Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events. Substantially more olanzapine-treated patients (66.5%) than haloperidol-treated patients (46.8%) completed 6 weeks of therapy. Statistically significant advantages of olanzapine treatment were related to 1) change in negative symptoms, 2) extrapyramidal symptom profile, 3) effect on prolactin levels, and 4) response rate.
                Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology, with a substantially more favorable safety profile, than haloperidol. It meets several of the criteria for a novel atypical antipsychotic agent. The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.
                Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.
                The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.
                These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia. The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.
                In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).
                Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.
                The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.
The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.