Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison

OBJECTIVE: This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness. METHOD: Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%. RESULTS: A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%). CONCLUSIONS: Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.     

Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study

OBJECTIVE: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. METHOD: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. RESULTS: The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder

OBJECTIVE: The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. METHOD: Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks. RESULTS: The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants. CONCLUSIONS: Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.     

Improvement in social functioning in outpatients with schizophrenia with prominent negative symptoms treated with olanzapine or risperidone in a 1 year randomized, open-label trial

GENERAL PURPOSE: To evaluate the social functioning of schizophrenic outpatients after switching to second-generation antipsychotics. METHODOLOGY: Multi-center, randomized, open-label, parallel, flexible-dose, 1-year study of schizophrenic outpatients with prominent negative symptoms (defined as a SANS Global score > or =10), previously treated with conventional antipsychotics. Patients were randomly assigned (1:1 ratio) to treatment with an initial dose of at least 10 mg/day olanzapine (N = 120) or at least 3 mg/day risperidone (N = 115). Dosage could be modified during the study according to clinical criteria. Social functioning was evaluated using the total and subscales scores of the Social Functioning Scale (SFS) (validated Spanish version). Other efficacy measures included the SANS, SAPS, and CGI-S scales. Response was defined in advance as a 30% improvement in the SANS Global score. RESULTS: The mean doses during the trial were 12.2 mg/day (S.D. = 5.8) of olanzapine and 4.9 mg/day (S.D. = 2) of risperidone. There were no significant baseline differences in SFS total scores or other relevant clinical variables. At 1 year, olanzapine-treated patients presented a mean improvement in SFS total scores (7.75) that were significantly higher (p = 0.0028) than for risperidone-treated patients (-0.92). Treatment with olanzapine resulted in a greater numerical improvement than risperidone in all SFS domains and reached statistical significance in such categories as social engagement or withdrawal (p = 0.01), independence (performance) (p = 0.0098), independence (competence) (p = 0.04), recreational activities (p = 0.0391), and occupation/employment (p = 0.0024) in which the greatest difference between the olanzapine and risperidone groups was found (0.86 vs. -3.06). Significantly more patients treated with olanzapine reached or surpassed the SFS typified total scores corresponding to a functional level that is representative of a sample of stabilized Spanish outpatients with schizophrenia without prominent negative symptoms (p = 0.0009). Associated factors were treatment with olanzapine and a 30% improvement or more in SANS global score or SAPS global score. CONCLUSIONS: Long-term treatment with olanzapine was associated with overall greater improvement in social functioning (as measured by SFS) compared to risperidone-treated patients.     

Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine

OBJECTIVE: Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder. METHOD: The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates. RESULTS: There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76). CONCLUSIONS: Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.     

A double-blind comparison of olanzapine versus risperidone in the acute treatment of dementia-related behavioral disturbances in extended care facilities

BACKGROUND: In addition to demonstrating their superiority to placebo, there is a need to compare the relative efficacy and side effects of atypical neuroleptics for the acute treatment of dementia-related behavioral disturbances in residents of long-term care facilities. METHOD: In a double-blind parallel study allowing dose titration over 14 days, 39 agitated persons with DSM-IV dementia who were residing in long-term care facilities were administered olanzapine (N = 20) or risperidone (N = 19) as acute treatment. Drug was administered once a day at bedtime. The initial dosages were olanzapine, 2.5 mg/day, and risperidone, 0.5 mg/day. Titration was allowed to maximum doses of olanzapine, 10 mg/day, and risperidone, 2.0 mg/day. The primary outcome measures were the Clinical Global Impressions scale (CGI) and the Neuropsychiatric Inventory (NPI). Data were gathered from 2000 to 2002. RESULTS: Both drugs produced significant reductions in CGI and NPI scores (p <.0001), but there was no significant difference between drugs. The mean olanzapine dose was 6.65 mg/day; for risperidone, the dose was 1.47 mg/day. The positive drug effect was not accompanied by decreased mobility, and there was improvement on a quality-of-life measure. The chief adverse events were drowsiness and falls. At baseline, 42% (16/38) of subjects in both groups had extrapyramidal symptoms that increased slightly, but not significantly, by the end of the study. CONCLUSION: Low-dose, once-a-day olanzapine and risperidone appear to be equally safe and equally effective in the treatment of dementia-related behavioral disturbances in residents of extended care facilities.     

Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial.

OBJECTIVE: The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD). METHOD: The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity. RESULTS: Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) ([1]) = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment. CONCLUSION: This trial did not confirm earlier findings in this population.     

Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression

BACKGROUND: Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination. METHOD: In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records. RESULTS: Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.     

Use of atypical antipsychotics in a Veterans Affairs hospital

In a retrospective chart review, efficacy and drug costs were compared in 91 consecutive outpatients receiving risperidone (n=70) or olanzapine (n=21) at the Veterans Affairs Medical Center in Syracuse, NY. Between-group differences in background characteristics, diagnoses (schizophrenia in more than half of each group) and antipsychotic efficacy [Clinical Global Impressions (CGI) scale scores] were not significant. The mean doses were 3.6+/-2.4 mg/day of risperidone and 10.7+/-7.6 mg/day of olanzapine. The VA costs of these mean doses were S3.32/day for risperidone and $6.67/day for olanzapine. Mean duration of treatment was significantly longer for risperidone (21 months) than for olanzapine (13 months). Incidence of parkinsonian symptoms (14% of both risperidone and olanzapine patients) and tardive dyskinesia (3% of risperidone patients and 5% of olanzapine patients) was similar in the two groups. Akathisia tended to occur more often in patients receiving olanzapine than risperidone (14% versus 3%, P=.08). The results of this retrospective survey indicate that, in comparable VA populations of patients with psychotic and other disorders, risperidone and olanzapine are equally efficacious but olanzapine may be more likely to produce akathisia and is twice as expensive as risperidone.     

Experience with the Atypical Antipsychotics—Risperidone and Olanzapine in the Elderly

There is paucity of published data regarding controlled trials with risperidone and olanzapine in elderly psychotic patients. Medical records of 151 hospitalized geropsychiatric patients (risperidone patients n = 114 and olanzapine patients n = 37) were analyzed for demographic data, target symptoms, doses, effects, side effects, comorbid medical conditions and concurrent medications. The mean age of the patients was 71 years. The male: female ratio was essentially the same for both groups. The mean daily dose was 3 mg for risperidone and 10 mg for olanzapine. 78% of the risperidone group and 75% of the olanzapine group appear to have responded to treatment. The discontinuation rates of medication was the same in both groups (22%). Adverse events were reported in 16–17% in both groups. It appears from this study that both risperidone and olanzapine are relatively safe and effective in geropsychiatric patients with comorbid medical illnesses. Controlled studies and head-to-head comparison studies are recommended.     

A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial

This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.     

Comparison of Risperidone and Olanzapine in Bipolar and Schizoaffective Disorders

OBJECTIVE: To compare risperidone and olanzapine for efficacy, tolerability, need for concomitant mood stabilizers, and cost of treatment in bipolar and schizoaffective disorders. METHOD: We conducted a retrospective chart review of 36 consecutive outpatients with DSM-IV bipolar or schizoaffective disorder seen in 3 settings who received risperidone or olanzapine for at least 1 month between May and August 1997. RESULTS: The mean +/- SD doses were 3.7 +/- 3.5 mg/day of risperidone and 12.0 +/- 5.4 mg/day of olanzapine. Between-treatment differences in patient characteristics, psychiatric history, Clinical Global Impressions scale ratings, and duration of treatment were not significant. Similar proportions of patients in the 2 groups reported side effects, including extrapyramidal symptoms, akathisia, tardive dyskinesia, and precipitation of mania by the respective drug. Patients in the olanzapine group received a significantly higher dose of concomitant lithium than those receiving risperidone (mean daily lithium doses: risperidone group, 750 +/- 150 mg; olanzapine group, 1211 +/- 186 mg; p =.006). The total daily acquisition cost per patient was $11.84 for olanzapine versus $5.81 for risperidone. CONCLUSION: Olanzapine and risperidone were equally efficacious and safe in the treatment of patients with bipolar or schizoaffective disorder, but treatment costs and dose of concomitant lithium were lower in risperidone-treated patients.     

International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia.

OBJECTIVE: The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder

OBJECTIVE: To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder. METHOD: One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point. RESULTS: Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint. CONCLUSIONS: Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.     

Comparison of risperidone and olanzapine in the control of negative symptoms of chronic schizophrenia and related psychotic disorders in patients aged 50 to 65 years

BACKGROUND: This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients. METHOD: Post hoc assessments were made in a subset of risperidone-treated (N = 19) and olanzapine-treated (N = 20) older patients (aged 50 to 65 years) from a large international, multicenter, parallel, double-blind, 28-week study of patients aged 18 to 65 years (N = 339) randomly assigned to receive risperidone (4-12 mg/day) or olanzapine (10-20 mg/day). Assessments were made using repeated-measures analysis. RESULTS: At both 8 weeks and 28 weeks, the magnitude of changes in Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores did not differ between treatment groups (8 weeks: risperidone, -6.5; olanzapine, -6.8, p = .866; 28 weeks: risperidone, -6.5; olanzapine, -7.0; p = .804). However, by the 8-week timepoint, olanzapine had reduced PANSS negative subscale scores significantly more than risperidone (-8.8 vs. -4.9, p = .032). By the 28-week endpoint, olanzapine had continued to maintain significantly greater reduction in baseline-to-endpoint PANSS negative scores (-8.1 vs. -3.5, p = .032) and led to significantly greater reduction in scores on the Scale for the Assessment of Negative Symptoms (SANS) dimensions of affective flattening (-5.2 vs. -0.6, p = .033) and alogia (-3.8 vs. -0.3, p = .007). Patients in the olanzapine treatment group also demonstrated numerically greater reduction of both SANS summary (-3.7 vs. -1.0, p = .078) and SANS composite scores (-14.1 vs. -4.1, p = .075). CONCLUSION: These data demonstrate that, in older patients with schizophrenia and related psychotic disorders, risperidone and olanzapine have approximately equal efficacy in controlling positive symptoms. However, olanzapine appears to be more efficacious in maintaining control over negative symptoms.     

Cost evaluation of risperidone compared with olanzapine

This study evaluated costs associated with risperidone and olanzapine treatment for schizophrenia. Data were collected from the Department of Veterans Affairs computerized database nine months before and nine months after patients began continuous treatment with risperidone (N=23) or olanzapine (N=47). Both agents were associated with significant reductions in psychiatric hospitalization costs. Median increases in antipsychotic costs were significantly higher for patients treated with olanzapine ($1,892) than for those treated with risperidone ($733). Mean dosages were 3.5 mg per day for the risperidone group and 18 mg per day for the olanzapine group. Although both treatments were associated with similar reductions in costs of psychiatric inpatient and outpatient care, it was significantly less expensive to prescribe risperidone than olanzapine.     

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。     

Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.

OBJECTIVE: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. METHOD: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score. RESULTS: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group. CONCLUSIONS: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.     

Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis

OBJECTIVE: This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.