Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, chi2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, chi2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, chi2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.     

Risperidone versus haloperidol in the treatment of acute exacerbations of chronic inpatients with schizophrenia: a randomized double-blind study.

The purpose of this study was to compare the efficacy and safety of risperidone and haloperidol in treatment-resistant chronic schizophrenic patients. Subjects (n = 78) who met DSM-III criteria for schizophrenia were randomly assigned to receive 6 mg/day of risperidone or 20 mg/day of haloperidol for 12 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS), and side-effects with the Treatment Emergent Symptom Scale (TESS). Risperidone produced a mean 39.8 +/- 24.1% reduction in total PANSS score compared to a mean 28.3 + 19.4% reduction in the haloperidol group (P < 0.05). Analysis of changes for the three subscores of the PANSS revealed that the general psychopathology and negative subscores were significantly improved in the risperidone group compared to the haloperidol group. As for the side-effects, the risperidone group showed a significantly lower TESS total score, as well as nervous system symptoms subscore and cardiovascular symptoms subscore, compared to the haloperidol group. Risperidone appears to be a more effective and better tolerated antipsychotic drug in treatment-refractory Chinese schizophrenia than haloperidol.     

利培酮和氟哌啶醇随机双盲治疗痴呆的行为和精神症状

目的 :评价利培酮和氟哌啶醇治疗痴呆的行为和精神症状的疗效和安全性。方法 :采用随机双盲对照研究 ,利培酮组 2 8例 ,剂量 (1.3±s 0 .5 )mg·d- 1,0 .5～ 2mg·d- 1。氟哌啶醇组 2 5例 ,剂量(2 .8± 0 .9)mg·d- 1,1～ 4mg·d- 1,疗程均 8wk。治疗前后进行阿尔采末病病理行为评分表 (BE HAVE AD)、Cohen Mansfield激越问卷 (CMAI)等量表评定及实验室检查。结果 :2组病人治疗后BEHAVE AD和CMAI评分显著下降 (P <0 .0 1) ,2组病人之间治疗后的BEHAVE AD和CMAI减分值无显著差异 (P >0 .0 5 )。 2组病人的不良反应均以锥体外系反应为主 ,利培酮组 2 3% ,氟哌啶醇组4 0 %。结论 :低剂量的利培酮和氟哌啶醇治疗BPSD疗效确切 ,病人耐受性好。     

Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol.

In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term.     

Olanzapine: an updated review of its use in the management of schizophrenia

Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. CONCLUSIONS: Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.     

利培酮联合碳酸锂治疗躁狂的临床研究

目的 评价利培酮在躁狂发作治疗中的疗效及安全性.方法 选取70例患者随机分为利培酮组和氟哌啶醇组进行对照研究,两组均联用碳酸锂.采用Bech-Rafaelsen评定量表（BRMS）及其减分率对疗效进行观察,同时观察两组的锥体外系反应.结果 两组均从第2周开始起效,但从第4周开始利培酮组的减分率明显大于氟哌啶醇组,而且氟哌啶醇组联用抗霍奇金药的例数是氟哌啶醇组的2倍多.结论 利培酮不仅可以治疗躁狂,且具有相当高的安全性.     

Risperidone (Risperdal): clinical experience with a new antipsychosis drug

Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychotic symptoms, probably more so than the older neuroleptics for both positive and negative symptoms. At clinically effective doses, risperidone causes no more extrapyramidal side-effects (EPS) than placebo; at higher doses EPS frequency increases in a dose-dependent manner. Since it became available in 1994, extensive experience with the drug supports favourable early impressions of efficacy and tolerability. Minimal sedation, relatively little weight gain and absence of anticholinergic manifestations contribute to the relative tolerability of risperidone as compared to older neuroleptics. However, risperidone is associated with hyperprolactinaemia which can result in amenorrhoea and sexual dysfunction. Compared to older neuroleptics, pharmacoeconomic studies have shown that use of risperidone is associated with reduced hospitalisation and direct cost savings. A recent study found equivalent efficacy between risperidone and clozapine for treatment-resistant patients. Two studies comparing risperidone and olanzapine have yielded positive but conflicting findings. The overall positive experience with risperidone has resulted in the drug being widely recommended as a first line treatment option for psychoses.     

国产利培酮对男性精神分裂症患者催乳素影响的临床研究

目的探讨国产利培酮（索乐）对精神分裂症男性患者血清催乳素（PRL）水平影响。方法将60例符合中国精神疾病障碍分类第3版（CCMD-3）精神分裂症诊断标准的男性患者随机分为利培酮（索乐）组（30例）和氟哌啶醇组（30例）,采用酶联免疫法测定两组治疗前后的PRL水平;采用PANSS量表评定两组临床疗效。结果①两组治疗8周末的PANSS量表评分均显著低于治疗前（P〈0．01）;②治疗前利培酮（索乐）组与氟哌啶醇组的PRL水平差异无统计学意义;治疗后利培酮（索乐）组与氟哌啶醇组的PRL水平均比治疗前升高,但两组间无显著性差异（P〉0．05）。结论国产利培酮（索乐）和氟哌啶醇均能升高患者的PRL水平,但两者差异无显著性。     

Effectiveness of haloperidol, risperidone and olanzapine in the treatment of first-episode non-affective psychosis: results of a randomized, flexible-dose, open-label 1-year follow-up comparison

The aim of this study was to investigate the long-term effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. This was a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiological and 3-year longitudinal intervention programme of first-episode psychosis conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy-four patients were randomly assigned to haloperidol (N?=?56), olanzapine (N?=?55), or risperidone (N?=?63) and followed up for 1 year. The primary effectiveness measure was all causes of treatment discontinuation. Effectiveness analyses were based on intend-to-treat populations. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The treatment discontinuation rate for any cause was higher with haloperidol than with risperidone and olanzapine (χ(2)?=?8.517; p?=?0.014). The difference in discontinuation rate between risperidone and olanzapine was not significant (χ(2)?=?0.063; p?=?0.802). There were no significant advantages of any of the three treatments in reducing the severity of psychopathology. Risperidone and olanzapine demonstrated higher effectiveness relative to haloperidol, but the three antipsychotics were equally effective in reducing the severity of psychopathology. Specific clinical programmes and the use of second-generation antipsychotics may enhance the effectiveness of antipsychotic treatments.     

氨磺必利与利培酮治疗首发精神分裂症的随机双盲双模拟平行对照试验

目的：探讨氨磺必利与利培酮治疗精神分裂症的疗效及安全性。方法：采用随机、双盲、双模拟、平行对照试验方法,将34例符合诊断标准的首发精神分裂症患者随机分为氨磺必利组和利培酮组,每组17例。氨磺必利和利培酮的治疗剂量分别为800～1 200 mg·d~（-1）和2～6 mg·d~（-1）。疗程均为8周。于治疗前及治疗第1,2,4,8周末采用阳性和阴性症状评定量表（PANSS）评定疗效,采用治疗中出现的症状量表（TESS）及实验室检查来评价安全性。结果：治疗后第2,4,8周末,两组PANSS总分较治疗前均显著降低（P〈0.05）;氨磺必利组和利培酮组总有效率分别为88.2%和82.4%,差异无统计学意义（P〉0.05）。两组不良反应发生率比较差异亦无统计学意义（P〉0.05）。结论：氨磺必利和利培酮对治疗精神分裂症的疗效相当,不良反应轻,值得临床应用。     

Differential efficacy of risperidone versus haloperidol in psychopathological subtypes of subchronic schizophrenia

The aim of this study was to evaluate the efficacy and tolerability of risperidone versus haloperidol in subchronic schizophrenia, using psychopathological subgroups of patients with negative or positive and mixed symptoms to analyse the possible differential efficacy of the drugs. A total of 33 patients diagnosed using DSM-IV criteria entered the 6 week double-blind study with either risperidone or haloperidol 5 mg/day. Twenty-nine patients completed at least 2 weeks of treatment and entered the last observation carried-forward analysis. Both treatments were effective in reducing total scores and positive and negative subscale scores on the Positive and Negative Scale for Schizophrenia (PANSS), with a significantly better extrapyramidal profile in the risperidone-treated group. When analysis was repeated in each treatment group by psychopathological subtype (negative vs positive-mixed subgroups based on the PANSS composite index), risperidone was significantly superior to haloperidol in the intention to treat analysis in the negative subgroup. Repeated measures multivariate analysis of variance showed a significantly greater improvement in the PANSS negative subscale scores of risperidone-treated patients in the negative subgroup and a significant improvement in the PANSS positive subscale scores in both psychopathological subtypes. Haloperidol was significantly effective only in reducing positive symptoms in the positive subtype. Our results indicate that risperidone may be proposed for first-line treatment of subchronic schizophrenia, in particular the negative subtype. Copyright 2001 John Wiley & Sons, Ltd.     

A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder

The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.     

Cost analysis of the treatment of schizophrenia in the UK. A simulation model comparing olanzapine, risperidone and haloperidol

OBJECTIVE: To compare the costs of 2 atypical drug therapies (olanzapine and risperidone) with one another and with a conventional antipsychotic (haloperidol) in the treatment of schizophrenia. DESIGN AND SETTING: The analysis is based on a simulation model with parameter values taken mainly from clinical trial data in patients with schizophrenia, and was conducted within a UK context. RESULTS: The 3 therapies are approximately cost neutral over a 5-year period (olanzapine 35,701 Pounds, risperidone 36,590 Pounds and haloperidol 36,653 Pounds). There is evidence of greater efficacy with the atypical drugs [average percentage of 5 years with Brief Psychiatric Rating Scale (BPRS) scores < 18: olanzapine 63.6%, risperidone 63.0% and haloperidol 52.2%]. The cost and efficacy differences between the 2 atypical drugs are too small to rank them in terms of cost effectiveness. Extensive sensitivity analysis does not change any of the main conclusions. CONCLUSIONS: Given evidence of efficacy gains to the atypical drugs, these represent cost-effective treatment options. Prospective data from nontrial treatment settings would help substantiate the model findings.     

Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis

Patients with schizophrenia suffer numerous relapses and rehospitalizations that are associated with high direct and indirect medical expense. Suboptimal therapeutic efficacy and, in particular, problems with compliance are major factors leading to relapse. Atypical antipsychotic agents offer improved efficacy and a lower rate of extrapyramidal adverse effects compared with conventional antipsychotic drugs. Long-acting intramuscular risperidone combines these benefits with improvements in compliance associated with depot injections. To assist decision making regarding the place of long-acting risperidone in therapy, a cost-effectiveness analysis of strategies involving first-line treatment with long-acting risperidone, oral olanzapine or depot haloperidol was performed from the perspective of the Belgian healthcare system. A decision tree model was created to compare the cost effectiveness of three first-line treatment strategies in a sample of young schizophrenic patients who had been treated for 1 year and whose disease had not been diagnosed for longer than 5 years. The model used a time horizon of 2 years, with health state transition probabilities, resource use and cost estimates derived from clinical trials, expert opinion and published prices. The four health states in the model were derived from an analysis of the literature. The principal efficacy measure was the proportion of patients successfully treated, defined as those who responded to initial treatment and who had none to two episodes of clinical deterioration without needing a change of treatment over the 2-year period. Comprehensive sensitivity analysis was carried out to test the robustness of the model. A greater proportion of patients were successfully treated with long-acting risperidone (82.7%) for 2 years, compared with those treated with olanzapine (74.8%) or haloperidol (57.3%). Total mean costs per patient over 2 years were 16,406 Euro with long-acting risperidone, 17,074 Euro with olanzapine and 21,779 Euro with haloperidol (year of costing 2003). The mean cost-effectiveness ratios were 19,839 Euro, 22,826 Euro and 38,008 Euro per successfully treated patient for long-acting risperidone, olanzapine and haloperidol, respectively. Results of the sensitivity analysis confirmed that the results were robust to a wide variation of different input variables (effectiveness, dosing distribution, patient status according to healthcare system). Long-acting risperidone was the dominant strategy, being both more effective and less costly than either oral olanzapine or depot haloperidol. Long-acting risperidone appears to represent a favourable first-line strategy for patients with schizophrenia requiring long-term maintenance treatment.     

注射用利培酮微球对精神分裂症患者认知功能的改善作用

 　目的：研究注射用利培酮微球对精神分裂症患者认知功能的改善作用。方法：60名受试者随机分为两组 ，分别给予注射用利培酮微球和氟哌啶醇片治疗。分别在基线期、第4，8，12和16周进行PANSS、认知功能测查，并分 析结果。结果：注射用利培酮微球组在威斯康星实验完成分类数从第4周起各时点较基线有显著性差异（P＜0.05），而 氟哌啶醇各时点数据与基线无显著差异，但组间比较无显著差异（P>005）。注射用利培酮微球组在持续性操作测验 的反应时间，数字广度评分上的表现优于氟哌啶醇组（P＜005），且注射用利培酮微球组持续性操作测验的反应时间 从第4周起，数字广度上第8，16周与基线比较有显著性差异（P＜005）。结论：注射用利培酮微球对执行功能、注意 及工作记忆有改善作用，且这种改善作用优于氟哌啶醇。     

Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol: a double-blind and randomized study

Rationale There are few data from systematic, double-blind clinical trials that have compared the effect of the typical and the atypical antipsychotics on serum prolactin (PRL) levels in patients with schizophrenia.Objectives The goal of this study was to compare the effect of risperidone and haloperidol on serum PRL and investigate the relationship between serum PRL levels and clinical response in patients with schizophrenia.Methods Seventy-eight inpatients with a diagnosis of schizophrenia (according to DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol after a 2-week washout period, using a randomized, double-blind design. Clinical efficacy was determined using the positive and negative syndrome scale (PANSS). Their serum PRL was assayed by means of radioimmunometric assay (RIA) between pre-treatment and post-treatment, and compared with 30 sex-matched and age-matched normal subjects.Results Both risperidone and haloperidol treatment significantly increased serum PRL levels in drug-free chronic schizophrenia patients (both P<0.001). Hyperprolactinemia induced by risperidone 6 mg/kg was comparable to levels produced by haloperidol 20 mg/day. Considering dose-adjusted serum PRL levels, risperidone treatment induced a significant elevation of PRL levels compared with haloperidol treatment at the haloperidol equivalent (P<0.001). Change in PRL levels at pre-treatment and post-treatment were related to positive symptom improvement seen in the risperidone group (r=0.51, P=0.016), but not in the haloperidol group (P>0.05). Female patients showed both a higher baseline and post-treatment PRL level and a greater increase in PRL than men (all P<0.05).Conclusions Risperidone is associated with a robust effect on prolactin secretion in contrast to the conventional antipsychotic haloperidol. Prolactin monitoring during risperidone treatment should be performed.     

奥氮平与利培酮对精神分裂症患者生活质量影响的对照研究

目的评价国产奥氮平与利培酮治疗精神分裂症的疗效、安全性及其对患者生活质量的影响。方法将78例首发精神分裂症患者随机分为奥氮平组和利培酮组,各39例,治疗8周,采用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)、生活质量综合评定问卷(GQOLI)分别评定患者的疗效及生活质量。结果两组PANSS总分治疗后均明显下降(P<0.01),组间差异则无显著性(P>0.05)。奥氮平组的显效率为66.67%、有效率为84.62%,利培酮组的显效率为61.54%、有效率为82.05%,两组比较无显著性差异(P>0.05)。两组GQOLI评分治疗8周末除物质生活维度无显著性变化外,其他各维度评分均显著性提高(P<0.05),而组间生活质量4个维度评分亦无显著性差异(P>0.05)。两组不良反应发生率低且程度轻,奥氮平组体重增加比例较高,而利培酮组锥体外系反应比例较高。结论奥氮平和利培酮对精神分裂症均有显著疗效,安全性高,能较好地提高患者的生活质量。     

The effects of excitotoxic hippocampal lesions in rats on risperidone- and olanzapine-induced locomotor suppression.

Previous studies have shown that excitotoxic hippocampal lesions in rats attenuate the ability of different doses of haloperidol, but not of clozapine, to suppress locomotor activity. The purpose of the present study was to determine if kainic acid-induced hippocampal damage reduces the degree of locomotor suppression produced by two relatively newer antipsychotic drugs, risperidone and olanzapine. Young adult male rats received bilateral intracerebroventricular infusions of the excitotoxin, kainic acid (KA), or vehicle and were tested for locomotor responses to drug treatment 30 days later. Infusions of KA produced neuronal loss in the CA3 region of the dorsal hippocampus in every rat. As reported previously, KA lesions reduced the ability of haloperidol (0.35 mg/kg) to completely suppress the locomotor activity elicited by amphetamine (1.5 mg/kg) relative to the effect of haloperidol in non-lesioned controls. Lesioned animals treated with a moderate dose of risperidone (1.4 mg/kg) also exhibited significantly more locomotor activity after amphetamine treatment in comparison to control animals. A trend toward greater activity was also observed in the lesioned group relative to the control group after olanzapine (3.0 mg/kg) injection (p =.09, 2-tailed). The locomotor effects of lower and higher doses of risperidone and olanzapine were not altered by kainic acid lesions. These data suggest that the locomotor-suppressive effects of moderate doses of risperidone and, perhaps, olanzapine involve hippocampal neurons, but that higher doses of each drug can suppress activity in a hippocampal-independent manner.     

Risperidone: clinical safety and efficacy in schizophrenia.

Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol.     

Effects of atypical neuroleptics on sustained attention deficits in schizophrenia: a trial of risperidone versus haloperidol.

To help determine whether sustained attention deficits as measured with the Continuous Performance Test (CPT) are stable vulnerability indicators of schizophrenia, we compared the CPT performance of schizophrenic patients before and after treatment with risperidone or haloperidol. In this double blind trial, 56 schizophrenic patients were randomly assigned to a 12-week regimen of either risperidone or haloperidol, after a 1-week washout period. The patients undertook two sessions of the CPT (undegraded and 25% degraded) twice, one at the end of the washout period and the other at the end of the study. Thirty-eight patients completed the study, 19 in each group. Both groups experienced significant improvements in clinical symptoms, and the risperidone group showed no change in the severity of extrapyramidal symptoms. Despite those improvements, the CPT performance indexes did not change significantly from the beginning to the end of the study. These findings indicate that sustained attention deficits might be stable vulnerability indicators of schizophrenia.