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.     

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.     

利培酮与氯氮平治疗精神分裂症对照研究

目的比较利培酮和氯氮平治疗精神分裂症的疗效和不良反应。方法将40例精神分裂症患者随机分成两组,利培酮组和氯氮平组各20例,于治疗前和治疗第2、4、6周末采用症状量表（PANSS）及副反应量表（TESS）评定疗效及不良反应。结果两组PANSS减分率比较差异无统计学意义（P〉0．05）,利培酮组不良反应少。结论利培酮与氯氮平治疗精神分裂症疗效相当,但利培酮不良反应少。     

利培酮与氯氮平治疗精神分裂症对照研究

目的 比较利培酮和氯氮平治疗精神分裂症的疗效和不良反应.方法 将40例精神分裂症患者随机分成两组,利培酮组和氯氮平组各20例,于治疗前和治疗第2、4、6周末采用症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应.结果 两组PANSS减分率比较差异无统计学意义(P>0.05),利培酮组不良反应少.结论 利培酮与氯氮平治疗精神分裂症疗效相当,但利培酮不良反应少.     

Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone.

The Brief Psychiatric Rating Scale (BPRS) anxiety/depression subscore has been used to assess affective symptoms in three studies (n = 612) comparing amisulpride (400-800 mg/day, n = 339) with haloperidol (15-20 mg/day, n = 160) and risperidone (8 mg/day, n = 113) in the treatment of acute exacerbations of schizophrenia. At endpoint, the mean improvement in the anxiety/depression subscore showed a significant (P = 0.011) difference in favour of amisulpride (5.6+/-6.1) compared with haloperidol (4.4+/-5.5) and risperidone (3.7+/-4.7). Amisulpride provided a significantly greater improvement compared both to haloperidol and risperidone in more severely depressed patients (BPRS anxiety/depression subscore > or = 16 at baseline, P = 0.001). This significant advantage in favour of amisulpride is seen from the 2nd week of treatment.     

帕利哌酮与利培酮治疗首发精神分裂症的临床疗效与安全性Δ

目的:比较帕利哌酮与利培酮治疗首发精神分裂症的临床疗效及安全性。方法:92例首发精神分裂症患者分为帕利哌酮(3～12 mg.d-1)组和利培酮(4～6 mg.d-1)组各46例,疗程为8周。于基线及服药2、4、6、8周末,采用阳性和阴性症状量表(PANSS)评定疗效、副反应量表(TESS)评定不良反应。结果:最终入组的患者为89例,其中帕利哌酮组45例,利培酮组44例,治疗4、6、8周末2组的PANSS总分、阳性症状评分、阴性症状评分和精神病理评分均显著降低(P<0.01)。治疗2周末,2组间PANSS总分、阳性症状评分和一般病理症状评分比较,有显著差异(P<0.01),阴性症状评分比较无显著差异(P>0.05)。治疗8周末帕利哌酮组PANSS总分减分率为(68.3±11.7)%,利培酮组为(67.8±12.1)%;帕利哌酮组有效率为71.1%,利培酮组为68.2%,2组疗效比较无显著差异(P>0.05)。帕利哌酮组锥体外系反应发生少于利培酮组(P<0.05)。结论:帕利哌酮治疗首发精神分裂症疗效与利培酮相当,且起效快、锥体外系反应少、安全性较好。     

帕利哌酮缓释片门诊治疗精神分裂症疗效及社会功能的临床研究

目的:探讨帕利哌酮缓释片对精神分裂症的疗效及安全性。方法:门诊确认的精神分裂症患者分为帕利哌酮缓释片治疗组(n=76)和利培酮对照组(n=79),共治疗4周,治疗前及治疗4周后分别应用阳性与阴性症状量表(PANSS)、个人和社会功能量表(PSP)和副反应量表(TESS)评定疗效及安全性。结果:帕利哌酮组治疗4周后PANSS总分及各因子评分低于基线,差异均具有统计学意义(P<0.05);帕利哌酮组PANSS总分及阴性症状评分均低于对照组,差异具有统计学意义(P<0.05)。治疗4周后,帕利哌酮组PSP评分较利培酮组有不同程度提高,差异具有统计学意义(P<0.05)。帕利哌酮组不良反应与利培酮组相当,均未见严重不良反应。结论:帕利哌酮缓释片可有效改善精神分裂症患者的阳性症状、阴性症状以及社会功能,安全性较高。     

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.     

Risperidone: a review of its use in the management of the behavioural and psychological symptoms of dementia

Risperidone is a benzisoxazole derivative which has proven efficacy against the positive and negative symptoms of schizophrenia. It has more recently been investigated and shown efficacy as a treatment for the behavioural and psychological symptoms associated with dementia in the elderly. Risperidone has pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the conventional antipsychotic haloperidol. Risperidone has antagonistic activity primarily at serotonin 5-HT2A and dopamine D2 receptors. In the first 2 large, well controlled trials of an antipsychotic agent used in the treatment of elderly patients with Alzheimer's dementia, vascular dementia or mixed dementia, risperidone 1 mg/day was at least as effective as haloperidol and superior to placebo, as assessed by the rating scales for global behaviour, aggression and psychosis. In extension phases of the 2 trials, clinical benefits were maintained for treatment periods of up to 1 year, with an incidence rate of tardive dyskinesia (2.6%) one-tenth of that seen with conventional antipsychotics. Risperidone, administered at a low dosage of 1 mg/day was associated with fewer extrapyramidal symptoms compared with haloperidol in elderly patients. Risperidone was well tolerated with no clinically relevant abnormalities in laboratory tests, vital signs or electrocardiogram results. Conclusion: The efficacy of risperidone has been demonstrated in the treatment of the behavioural and psychological symptoms associated with dementia in the elderly. Preliminary results from 1-year extension studies confirm the favourable efficacy and tolerability profile of risperidone 1 mg/day. Although head to head studies with other atypical antipsychotic agents are required and the long term use of the drug requires clarification, risperidone represents a generally well tolerated and effective treatment in the management of dementia-associated behavioural and psychological symptoms in the elderly.     

利培酮治疗青少年精神分裂症疗效观察

目的探讨利培酮治疗儿童精神分裂症疗效及不良反应。方法对86例首发儿童精神分裂症患儿给予利培酮治疗8周,分别以PANSS量表和TESS量表评定疗效及不良反应。结果利培酮治疗儿童精神分裂症显效率为74.42%,阳性症状起效时间为2周左右,阴性症状起效时间为4周。治疗剂量0.75~7 mg/d,平均(2.63±1.88)mg/d。结论利培酮对儿童精神分裂症阳性、阴性症状均有效,不良反应较少,但要注意个体化用药原则。     

帕利哌酮与利培酮治疗精神分裂症患者对照研究

目的探讨帕利哌酮与利培酮治疗精神分裂症的疗效与安全性。方法 60例精神分裂症患者随机分为2组各30例,分别给予帕利哌酮与利培酮治疗8周。采用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)评定疗效及不良反应。结果帕利哌酮组显效率80%,利培酮组显效率83.3%,差异无统计学意义(P>0.05)。2组在治疗第2周起PANSS总分均有显著下降(P<0.05和P<0.01),而2组间在治疗各周差异均无统计学意义(P>0.05)。利培酮组的锥体外系不良反应高于帕利哌酮组,差异有统计学意义(P<0.01)。结论帕利哌酮与利培酮治疗精神分裂症的疗效相当。     

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。     

阿立哌唑与利培酮治疗精神分裂症的双盲双模拟多中心研究

目的:研究阿立哌唑与利培酮治疗精神分裂症的疗效与安全性。方法:采用CCMD-3精神分裂症的诊断标准,223例精神分裂症患者随机分为阿立哌唑组(109例)和利培酮组(114例),治疗6周。治疗前后用阳性症状和阴性症状量表(PANSS)、临床疗效总评量表(CGI)和副反应量表(TESS)、锥体外系副反应量表(ESRS)评定疗效和安全性。结果:经6周治疗,223例患者完成研究。阿立哌唑组治愈率31.8%,有效率83.3%;利培酮组治愈率39.1%,有效率87.5%(P>0.05)。两组治疗前后PANSS总分、阳性症状、阴性症状、一般精神病理症状评分比较有显著差异(P<0.01)。阿立哌唑组阴性症状分治疗6周末下降较利培酮组明显,有显著差异(P<0.05)。治疗4周末、6周末阿立哌唑组反应缺乏分下降,和利培酮组比较有显著差异(P<0.05)。治疗4,6周末TESS评定阿立哌唑不良反应发生率低于利培酮(P<0.05)。阿立哌唑组主要不良反应是锥体外系副反应、失眠、头昏等。结论:阿立哌唑对精神分裂症患者安全有效。     

The effect of risperidone treatment on superoxide dismutase in schizophrenia

Some reports have shown that schizophrenia is accompanied by the abnormal metabolism of free radicals. The purpose of this study was to investigate the effect of the atypical antipsychotic drug risperidone on blood superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, and to explore the relationship between changes in SOD and the therapeutic outcome. Forty-one inpatients with diagnosed schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone at a fixed dosage of 6 mg/d after a 2-week washout period. Clinical efficacy was determined with the Positive and Negative Syndrome Scale (PANSS). Blood SOD was assayed by radioimmunoassay (RIA) in schizophrenic patients before and after the 12-week treatment, and the values were compared with those of 50 age-, sex-, and smoking-matched subjects without schizophrenia. Risperidone treatment significantly decreased the initially high blood SOD levels in schizophrenia. There was a significantly positive relationship between the change in SOD at pretreatment and posttreatment and the reduction in the PANSS negative subscore. These findings suggest that risperidone treatment significantly decreased the blood SOD levels of schizophrenic patients, a change which may be associated with the diminishment of symptoms. The limitations of this study are the measurement of SOD levels by RIA rather than biochemical assay; the 2-week washout, which may not be adequate; and the measurement of only SOD enzyme and not the other antioxidant enzymes.     

No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial

Noncompliance and poor outcome in patients with schizophrenia are closely related to the negative symptoms secondary to antipsychotics. No controlled study has evaluated whether amisulpride and aripiprazole induce negative symptoms. The aim of this study was to assess the effects of single doses of amisulpride, aripiprazole, haloperidol, and risperidone in healthy volunteers. Seventy-eight young volunteers took part in this double-blind, randomized, placebo-controlled, parallel study of four antipsychotics: 400 mg amisulpride, 10 mg aripiprazole, 3 mg haloperidol, and 2 mg risperidone. Assessments of negative symptoms were done 4 h after administration using both subjective rating scales (Neuroleptic Induced Deficit Syndrome Scale and Subjective Deficit Syndrome Scale) and an objective rating scale (Scale for the Assessment of Negative Symptoms). Risperidone only produced significant increases on the avolition score of the Neuroleptic Induced Deficit Syndrome Scale and blunted affect and alogia scores of the Scale for the Assessment of Negative Symptoms compared with placebo. The effect on blunted affect persisted after controlling for mental sedation. Amisulpride, aripiprazole, and haloperidol did not induce negative symptoms. Aripiprazole and risperidone induced mild extrapyramidal symptoms. The most common adverse events were somnolence and cognitive slowing. These data indicate that a single risperidone dose induces negative symptoms in normal volunteers, whereas amisulpride, aripiprazole, and haloperidol do not. These characteristics of antipsychotics should be considered when choosing optimal drugs for patients with psychosis.     

利培酮与氯氮平治疗精神分裂症比较

目的 :比较利培酮和氯氮平治疗精神分裂症的疗效和安全性。方法 :利培酮组 30例 (男性 12例 ,女性 18例 ,年龄 34a±s 10a ,BPRS评分 5 4分± 5分 )用利培酮 1～ 8mg/d ,po ,bid ;氯氮平组 30例 (男性 14例 ,女性 16例 ,年龄 33a± 11a ,BPRS评分 5 5分± 5分 )用氯氮平 5 0～ 40 0mg/d ,po ,bid ;均以BPRS ,TESS评定观察 8wk。结果 :利培酮组有效率为 83% ,氯氮平组为 80 % (P >0 .0 5 )。利培酮组对阴性症状起效较早 ,对兴奋躁动控制较差。利培酮组较多见副作用为锥体外系症状 ( 2 7% ) ,与氯氮平组 ( 3% )比较差异有显著意义 (P <0 .0 5 ) ,其他副作用较少而轻。结论 :利培酮与氯氮平疗效相似 ,适宜剂量 (≤ 4mg/d)的利培酮是一种安全有效的抗精神病药。     

利培酮与奋乃静治疗酒精所致精神障碍对照研究

目的探讨利培酮治疗酒精所致精神障碍的临床疗效及安全性。方法将符合条件的70例酒精所致精神障碍患者随机分成利培酮组35例和奋乃静组35例,进行6周系统治疗,采用PANSS、TESS量表分别评定疗效及不良反应。结果利培酮组有效率91.4%;奋乃静组有效率77.1%,两组疗效有显著性差异（P〈0.05）;两组治疗前后PANSS评分比较具有显著性差异（P〈0.01）,对阳性症状、阴性症状及一般精神病理症状均有良好疗效;而两组间在治疗4周、6周阴性症状分及6周末总分利培酮显著低于奋乃静（P〈0.05）;利培酮引起的锥体外系症状较奋乃静低（P〈0.05）。结论利培酮对酒精所致精神障碍的疗效优于奋乃静,且不良反应少。     

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.     

Effects of risperidone on affective symptoms in patients with schizophrenia

The effects of risperidone on affective symptoms were determined by an analysis of pooled data from six double-blind trials of risperidone versus haloperidol in 1254 patients with chronic schizophrenia. Symptoms indicating mania were assessed by the Positive and Negative Syndrome Scale (PANSS) excitement and grandiosity items and by the excited cluster (excitement, hostility, uncooperativeness, and poor impulse control); anxious / depressive symptoms were assessed by the PANSS anxious / depressive cluster (somatic concern, anxiety, guilt feelings, and depression). Mean change scores from baseline to endpoint were compared in patients receiving risperidone, haloperidol or placebo by analysis of variance with factors for trial and baseline score included in the model. In all patients, change scores on excitement and grandiosity items and excited and anxious / depressive clusters were significantly greater for risperidone than for haloperidol or placebo. Dropouts due to inefficacy were less frequent with risperidone (5 of 59; 8%) than with haloperidol (7 of 38; 18%) or placebo (8 of 10; 80%). In patients with anxious / depressive symptoms at baseline (anxiety / depression cluster score > or = the median), anxiety / depression scores decreased significantly more with risperidone than with haloperidol, and symptom reduction occurred faster with risperidone. These results are consistent with previous reports and suggest that risperidone is more efficacious than haloperidol for affective symptoms in patients with schizophrenia.     

利培酮合并小剂量阿立哌唑治疗女性精神分裂症对照研究

目的：探讨利培酮联合小剂量阿立哌唑治疗女性精神分裂症的疗效及对泌乳素的影响。方法：70例女性精神分裂症患者随机分为利培酮联合小剂量阿立哌唑治疗组和利培酮治疗组。治疗前及治疗后第2、4、8周末采用PANSS评定临床疗效。采用TESS评定药物不良反应。结果：利培酮联合小剂量阿立哌唑治疗组有效率为85.7%,利培酮组治疗有效率为88.6%,无显著性差异;两组不良反应（包括高泌乳素血症相关的泌乳、闭经）差异无统计学意义。结论：利培酮联合小剂量阿立哌唑治疗女性精神分裂症疗效及耐受性均好,未出现高泌乳血症相关症状,利培酮治疗女性精神分裂症时不必要预防应用阿立哌唑。