Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia.

BACKGROUND: There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted. METHODS: A subpopulation of patients (n = 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, 6-week study assessing the efficacy and safety of olanzapine and haloperidol were examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted. RESULTS: Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale, and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale total (p = .006), PANSS total (p = .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but significance was not reached in the completers analysis (p = .093). Mean doses (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6 mg/day, respectively. CONCLUSIONS: Olanzapine was superior to haloperidol for key symptom domains and parkinsonian side effects. Implications of these data for the therapeutics of this severely ill subgroup are discussed.     

The effects of olanzapine on the 5 dimensions of schizophrenia derived by factor analysis: combined results of the North American and international trials

BACKGROUND: The choice of drug to treat a patient with schizophrenia is one of the most critical clinical decisions. Controversy exists on the differential efficacy of olanzapine. DATA SOURCES AND STUDY SELECTION: Raw data from all 4 registrational double-blind, random-assignment studies of olanzapine compared with placebo or haloperidol were obtained from Eli Lilly and Company for this meta-analysis. METHOD: Analysis of covariance of the intent-to-treat last-observation-carried-forward endpoint scores was used to assess efficacy on Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) total scores and the 5 factors derived by factor analysis (negative symptoms, positive symptoms, disorganized thoughts, impulsivity/hostility, and anxiety/depression). RESULTS: Olanzapine produced a statistically significantly greater reduction in schizophrenic symptoms than haloperidol (p < .05) on total scores on the BPRS and PANSS on each of the 5 factors as well as on almost all items. Olanzapine induced a response at a rate equal to that induced by haloperidol in the first few weeks, but by the end of the study produced a greater percentage of responders. Compared with haloperidol, olanzapine produced a somewhat greater response on symptoms responsive to haloperidol, but a markedly better response on symptoms unresponsive to haloperidol. This difference favoring olanzapine occurred to an equal degree in all subgroups examined. The incidence of parkinsonism or akathisia following olanzapine treatment was extremely low and not statistically distinguishable from placebo. CONCLUSION: Olanzapine produced a greater improvement than haloperidol particularly by benefiting a much larger number of items or factors. Extrapyramidal side effects and akathisia during olanzapine treatment were statistically indistinguishable from effects seen with placebo.     

Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder

CONTEXT: 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. OBJECTIVE: 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. DESIGN AND SETTING: 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). MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSIONS: 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.     

Olanzapine treatment of residual positive and negative symptoms

OBJECTIVE: Olanzapine has been hypothesized to have superior efficacy in patients with treatment-resistant schizophrenia. The authors examined the comparative efficacy and safety of olanzapine and haloperidol in outpatients with partially responsive schizophrenia. METHOD: Sixty-three outpatients with schizophrenia who met retrospective and prospective criteria for either residual positive or residual negative symptoms entered a 16-week double-blind, parallel-groups comparison of olanzapine and haloperidol. RESULTS: There were no significant differences between the two drugs in their effect on positive or negative symptoms. There were no significant differences between the two treatment groups on measures of social and functional outcome. Olanzapine-treated patients had a significant reduction in extrapyramidal symptoms and subjective measures of stiffness and dry mouth, but the increases in systolic blood pressure and weight in olanzapine-treated patients were significantly greater than they were in haloperidol-treated patients. CONCLUSIONS: Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.     

奥氮平与氯氮平治疗难治性精神分裂症对照研究

目的评价奥氮平治疗难治性精神分裂症的疗效及安全性。方法将64例难治性精神分裂症患者随机分为研究组和对照组,分别予以奥氮平和氯氮平治疗8周,采用PANSS量表和TESS量表评定疗效和不良反应。结果奥氮平组治疗前后PANSS减分率为39.3%,有效率为72.8%;氯氮平组治疗前后PANSS减分率为36.6%,有效率为59.4%。奥氮平组未见严重的不良反应。结论奥氮平与氯氮平治疗难治性精神分裂症均有良好疗效,奥氮平的副作用小,病人依从性好。     

Effective resolution with olanzapine of acute presentation of behavioral agitation and positive psychotic symptoms in schizophrenia

Behavioral agitation and prominent positive psychotic symptoms often characterize the acute presentation of schizophrenia. The clinical treatment goal is a rapid control of these symptoms. The relative efficacy of olanzapine, a novel antipsychotic drug, was compared with that of the conventional antipsychotic drug haloperidol. A post hoc analysis conducted on a large multicenter, double-blind, 6-week study of acute-phase patients with DSM-III-R schizophrenia or schizophreniform or schizoaffective disorders treated with olanzapine (5-20 mg/day) or haloperidol (5-20 mg/day) assessed the treatment effects on agitation (Brief Psychiatric Rating Scale [BPRS] agitation score) and positive symptoms (BPRS positive symptom score). Overall, olanzapine-treated patients experienced significantly greater improvement in behavioral agitation than did haloperidol-treated patients (last observation carried forward [LOCF]; p < .0002). Both groups showed similar reductions in agitation scores during the first 3 weeks of therapy; olanzapine was associated with significantly greater improvements at weeks 4, 5, and 6 (observed cases [OC]). Similarly, patients with predominantly positive psychotic symptoms experienced significantly greater improvement in BPRS positive symptom scores with olanzapine compared with haloperidol (LOCF; p = .013). In olanzapine-treated patients, improvement in BPRS agitation and positive symptom scores was significantly greater at weeks 4, 5, and 6 (agitation scores, p < or = .01; positive symptom scores, p < .05) (OC). These data suggest that olanzapine may be considered a first-line treatment for the patient in an acute episode of schizophrenia.     

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia

OBJECTIVE: The efficacy and safety of olanzapine were compared with those of ziprasidone. METHOD: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight. RESULTS: The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level. CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.     

Olanzapine and haloperidol in first episode psychosis: two-year data

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.     

A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia

BACKGROUND: Previous studies have reported that hippocampal volumes correlate with symptom severity in schizophrenia. This longitudinal study measured changes in symptoms and hippocampal volume in patients switched from typical antipsychotics to olanzapine. METHODS: MRI scans were acquired from patients with chronic schizophrenia (n=10) and healthy volunteers (n=20). At baseline, patients were treated with typical antipsychotics for at least one year, then switched to olanzapine, and rescanned approximately one year later. RESULTS: Olanzapine treatment resulted in no significant change in right or left hippocampal volume. Individual changes in right hippocampal volume correlated significantly with changes in symptoms. CONCLUSIONS: Hippocampal volume change may serve as a marker of symptom change in patients on olanzapine.     

Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy.

BACKGROUND: A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. METHODS: The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer). RESULTS: Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech. CONCLUSION: Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.     

奥氮平与氯丙嗪治疗以阳性症状为主的精神分裂症对照研究

目的比较奥氮平与氯丙嗪治疗以阳性症状为主的精神分裂症的疗效及安全性。方法将126例精神分裂症患者随机分为奥氮平组和氯丙嗪组，共治疗8周。用临床疗效和阳性症状量表（SAPS）评定疗效，用不良反应量表（TESS）评定不良反应。结果奥氮平组痊愈率明显高于氯丙嗪组（χ^2=4．91，P〈0．05）；且起效明显较氯丙嗪组快（t=2．46，P〈0．05）；不良反应发生率和严重程度均较氯丙嗪组低而轻，亦有显著性差异（P〈0．05）。结论奥氮平对以阳性症状为主的精神分裂症疗效较好，起效快，不良反应少而轻。     

A prospective,open-label trial of olanzapine in adolescents with schizophrenia

BACKGROUND: Olanzapine is an atypical antipsychotic that has efficacy in adults with psychotic disorders. This preliminary study examined the effectiveness of olanzapine in adolescents with schizophrenia or its related conditions. METHOD: Adolescents aged 12-17 years (inclusive) with a diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder were enrolled in this 8-week, open-label, outpatient study. The Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), and the Children's Global Assessment Scale (CGAS) were administered as outcome measures. Extrapyramidal side effects were assessed at each visit. Olanzapine was initiated at a dose of 2.5 mg/day and could be increased to a maximum total daily dose of 20 mg. RESULTS: Sixteen participants with a mean age of 13.8 (SD = 1.5) years were treated. Significant improvements were found in the PANSS, CGI severity, and CGAS scores. Reductions in both positive and negative symptoms were found. Increased appetite and sedation were the most frequently reported side effects. Two subjects required treatment for extrapyramidal side effects. CONCLUSIONS: Psychotic symptoms significantly improved during study. Overall, olanzapine was well tolerated. Future studies are needed to confirm these findings, to assess long-term treatment outcomes, and to compare the effectiveness of olanzapine with that of other antipsychotics.     

奥氮平治疗精神病的疗效，副反应与血药浓度的关系

目的:分析奥氮平治疗精神病的疗效,副反应与血药浓度的关系.方法:用高效液相法测定病人的血药浓度,用阳性及阴性症状量表(PANSS),简明精神病评定量表(BPRS),社会功能缺陷筛选量表(SDSS)及副反应量表(TESS)评定其疗效和副作用.结果:奥氮平能显著降低阳性及阴性症状评价,且副反应轻微,剂量相同时,奥氮平血药浓度的个体差异较大,85%的病人的血药浓度在25-160nmol/L之间,其有效率为81.8%,浓度剂量的比值(C/D)与疗效呈正相关,结论:奥氮平能有效的治疗精神病,并改善社会功能障碍,25nmol/L是奥氮平适宜血药浓度的低限.奥氮平C/D值高的病人疗效好.     

Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.

BACKGROUND: The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo. METHODS: This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks. RESULTS: In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001). CONCLUSIONS: This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.     

奥氮平治疗难治性精神分裂症临床观察

目的：评价奥氮平对难治性精神分裂症的疗效与不良反应。方法：对难治性精神分裂症80例换用奥氮平治疗24周。用阳性症状和阴性症状量表(PANSS)评定疗效，用副反应量表(TESS)及锥体外系副反应量表(ESRS)评定不良反应。结果：PANSS量表总分及各分量表评分疗后均有显著下降。最常见的不良反应是体重增加。结论：奥氮平对难治性精神分裂症疗效肯定，不良反应较轻。     

The efficacy of a rapid-acting intramuscular formulation of olanzapine for positive symptoms

Rapid tranquilization of acutely psychotic patients with schizophrenia is usually carried out using typical antipsychotic agents. The objective of such treatment is to control agitation, not to treat psychosis, which usually responds only after a few weeks of treatment. An intramuscular formulation of the atypical antipsychotic olanzapine was developed for treatment of agitation in acutely psychotic patients. Studies conducted to assess control of agitation in schizophrenia also investigated the positive symptom efficacy of olanzapine when used to provide rapid tranquilization. This article summarizes the results of 3 clinical trials with intramuscular olanzapine with regard to positive symptom efficacy as measured by the Brief Psychiatric Rating Scale (BPRS; 0-6 scale) positive subscale. In 2 open-label trials, patients treated with intramuscular olanzapine experienced a mean decrease from baseline in BPRS positive subscale score. In 1 double-blind clinical trial of intramuscular olanzapine versus intramuscular haloperidol and intramuscular placebo, the mean decrease from baseline in BPRS positive subscale score for patients treated with intramuscular olanzapine was statistically significant (p < .05). In all 3 studies, positive symptom improvement continued following transition to oral olanzapine. These results suggest that intramuscular olanzapine has positive symptom efficacy early in the course of treatment and may provide a smooth transition to maintenance therapy with oral olanzapine.     

Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated with olanzapine or haloperidol

Previous clinical trials have clearly shown the superiority of olanzapine to haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic patients. The primary purpose of this study was to compare EPS profiles in Japanese schizophrenic patients treated with an atypical antipsychotic, olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of eight individual parameters and one global assessment (overall severity), was used to evaluate 182 patients enrolled in this 8-week study. The primary safety analysis was maximum change (that could be either a decrease or increase) from baseline in DIEPSS total score. Secondary analyses included change from baseline to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in DIEPSS total score, and the rank sum of the maximum change (that could be either a decrease or increase) from baseline in the DIEPSS individual items. Incidence of treatment-emergent EPS adverse events using the DIEPSS scale was also analyzed. The olanzapine group showed statistically significant superiority to the haloperidol group on the primary analysis (p<0.001). Secondary analyses also demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia and overall severity scores (all p< or =0.014). Categorical analysis of treatment-emergent akathisia and parkinsonism syndromes at endpoint showed improvement in the olanzapine group but worsening in the haloperidol group. The results from this study suggest that olanzapine, as in Caucasian populations, is a safe treatment in Japanese patients chronically ill with schizophrenia.     

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.     

奥氮平合用氯硝西泮治疗精神分裂症急性精神运动性兴奋的研究

目的：观察奥氮平合并氯硝西泮治疗精神分裂症急性精神运动性兴奋的疗效与不良反应。方法：65例精神分裂症急性期兴奋患者,随机分为口服奥氮平合并肌内注射氯硝西泮组（奥氮平组）34例和肌内注射氟哌啶醇组（氟哌啶醇组）31例治疗,疗程7 d。以阳性与阴性症状量表兴奋激越项目（PANSS-EC）和治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：奥氮平组与氟哌啶醇组疗效相当,差异无显著性（P〉0.05）。两组急性兴奋症状均获明显改善,氟哌啶醇组不良反应发生率高于奥氮平组（P〈0.05）。结论：奥氮平合并氯硝西泮可有效治疗精神分裂症患者急性期精神运动性兴奋,疗效与氟哌啶醇相当,不良反应明显少于氟哌啶醇。     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: 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. METHOD: 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). RESULTS: 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. CONCLUSIONS: 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.