An open study of risperidone liquid in the acute phase of schizophrenia

An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity.     

Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.     

利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的对照研究

目的：探讨利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的临床疗效以及安全性。方法将80例以阴性症状为主的慢性精神分裂症患者随机分为合用组和单用组,疗程12周,采用阳性和阴性症状量表（PANSS）和治疗中出现的症状量表（TESS）评定疗效和安全性。结果合用组显效率77.5%,单用组显效率55%。治疗后两组PASS评分均较治疗前有显著性下降,差异有统计学意义（P〈0.01）。治疗后2、4、8、12周末,合用组阴性因子分较单用组明显下降,差异有统计学意义（P〈0.05）。两组不良反应差异无统计学意义（P〉0.05）。结论利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状起效快、疗效好,不良反应少。     

阿立哌唑与利培酮治疗精神分裂症阴性症状对照研究

目的：比较阿立哌唑与利培酮治疗精神分裂症阴性症状的临床疗效。方法：阿立哌唑组60例,剂量范围10-30mg／d,利培酮组66例,剂量范围4—6mg／d,采用阳性症状与阴性症状量表（PANSS）评估临床疗效,用不良反应量表（TESS）评估不良反应。结果：阿立哌唑、利培酮治疗前后PANSS量表阳性因子、阴性因子、一般精神病症状因子分的差异有显著性,阿立哌唑与利培酮组间的PANSS各因子差异无显著性,阿立哌唑组不良反应小。结论：阿立哌唑与利培酮治疗精神分裂症阴性症状均有较好的疗效,阿立哌唑的安全性更好。     

帕潘立酮与利培酮用于精神分裂症的对比分析

目的探讨帕潘立酮与利培酮片治疗精神分裂症的效果和不良反应。方法60例精神分裂症患者随机分为观察组和对照组各30例,分别给予帕潘立酮与利培酮治疗,疗程8周。分别于治疗前和治疗1、2、4和8周采用阳性与阴性症状量表（PANSS）评定疗效;以治疗中出现的症状量表评定不良反应。结果治疗后两组PANSS计分均比治疗前显著下降（均P〈0．01）;观察组阴性症状计分在治疗4周与8周时明显比对照组更低（均P〈0．05）。观察组显效率（70％）明显高于对照组（47％）,两组有效率（90％与80％）差异无统计学意义（P〉0．05）。结论帕潘立酮是安全有效的抗精神病药物,对阴性症状的改善尤为显著。     

利培酮对首发精神分裂症患者的疗效观察及与血浆催乳素水平的相关性研究

目的探讨非典型抗精神病药利培酮对首发精神分裂症患者血浆催乳素(PRL)水平的影响及其与疗效的关系。方法对30例符合CCMD-Ⅲ诊断标准的首发精神分裂症患者(治疗组) 在治疗前后及30例健康自愿者(对照组)的血浆PRL水平用放射免疫法进行检测。用利培酮治疗12 周,采用阳性和阴性症状量表(PAN SS)在治疗前后分别进行评定。结果患者组治疗前血浆PRL水平低于对照组,差异有统计学意义(P<0．05);治疗组治疗后血浆PRL水平明显高于治疗前(P< 0．01);治疗前、后在PAN SS总分及其因子分上差异均有显著性意义(P<0．05)。治疗后PRL水平较高、治疗前后差异较大或治疗前PRL水平较高者,疗效较好,尤其是阳性症状改善明显。结论利培酮治疗明显增加血浆PRL水平;且治疗前后血浆PRL水平与疗效相关,主要与阳性症状的疗效有关。     

精神分裂症阳性和阴性症状患者奥氮平治疗疗效与血浆BDNF关系研究

目的 研究阳性症状和阴性症状精神分裂症患者奥氮平治疗前后血浆BDNF水平的变化。方法 按入组和排除标准分别募集阳性、阴性症状精神分裂症患者以及健康对照,2组精神分裂症患者均接受奥氮平治疗,治疗前后PANSS量表得分变化评价奥氮平治疗效果,ELISA法测定病例组治疗前后以及对照组血浆BDNF水平,并比较差异。结果 阳性症状精神分裂症患者治疗前后PANSS得分与血浆BDNF水平均呈显著负相关(P<0.01);治疗前血浆BDNF明显低于对照组(P<0.01);奥氮平治疗效果为好或中的患者,治疗后血浆BDNF水平比治疗前显著升高(P<0.01),而治疗无效的患者,治疗前后血浆BDNF差异无统计学意义。阴性症状患者奥氮平治疗前后PANSS得分与血浆BDNF水平均无明显相关性,且治疗前后血浆BDNF水平差异无统计学意义。结论 血浆BDNF可作为判断阳性症状精神分裂症患者奥氮平治疗是否有效的参考指标。     

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.     

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。     

Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders

A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels.     

Amisulpride: progress and outcomes

Amisulpride is a unique atypical antipsychotic that selectively blocks D2 and D3 receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission, and postsynaptically in the limbic areas, possibly reducing it. Thus dopaminergic over-activity in the frontal cortex, and under-activity in the limbic areas, can be treated simultaneously, alleviating both positive and negative symptoms of schizophrenia, respectively. In acute schizophrenia, amisulpride is at least as effective as haloperidol, with a greater number of patients responding to treatment as determined by Clinical Global Impression (CGI scores (p = 0.014). In addition, amisulpride is associated with a lower incidence of extrapyramidal symptoms (EPS) as determined by Simpson-Angus scores (SAS) when compared with haloperidol (p = 0.0053). Amisulpride showed similar efficacy to risperidone as determined by the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptom Score (PANSS) positive subscale; a trend towards greater improvement of negative symptoms as determined by PANSS negative subscale compared with risperidone; and similar levels of EPS. Amisulpride uniquely benefits patients with negative symptoms and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/long-term treatment as demonstrated in studies of up to 12 months. Amisulpride demonstrates greater improvement in controlling symptoms compared to haloperidol. In terms of the relevance of the effects, a superiority is observed for quality of life, social adaptation and functioning as measured by the Quality of Life Scale (QLS), Clinical Glocal Impression scale (CGI) and Functional Status Questionnaire (FSQ) scales. Amisulpride also has one of the lowest potentials of all the antipsychotic agents for weight gain. The clinical evidence for amisulpride supports its earlier pre-clinical potential, showing it to be an atypical antipsychotic agent with specific clinical advantages.     

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.     

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。     

国产齐拉西酮与利培酮治疗精神分裂症的对照研究

目的:以利培酮为对照,探讨齐拉西酮治疗精神分裂症的疗效和安全性.方法:将70例符合CCMD-3诊断标准的精神分裂症病人随机分为两组,分别给予齐拉西酮和利培酮治疗8周.于治疗前和治疗后2、4、8周末采用阳性症状和阴性症状量表(PANSS)评定临床疗效,副反应量表(TESS)评定副反应.结果:治疗8周后,两组疗效近似(P＞...     

抗抑郁药文拉法辛对精神分裂症阴性症状、社会功能恢复的临床疗效研究

目的:探讨抗抑郁药文拉法辛对精神分裂症患者的治疗效果。方法:回顾性分析2013年11月-2015年1月收治的64例精神分裂症患者的临床资料,其中,对照组采用利培酮治疗,而观察组采取文拉法辛联合利培酮治疗,比较2组患者的阴性症状、社会功能恢复情况以及不良事件发生情况。结果:治疗后,观察组与对照组患者的PANSS阴性症状、PSP评分均较治疗前出现明显改善,且在12周时,观察组患者的以上指标改善效果均优于对照组,组间差异具有统计学意义(P<0.05);2组不良反应发生率最高的主要为锥体外系副反应但组间各项相比,差异均无统计学意义(P>0.05)。结论:抗抑郁药文拉法辛可有效改善精神分裂症患者的阴性症状,提高患者的认知能力,从而较大程度改善患者的社会功能,促进患者的预后,其疗效显著且安全可靠,值得临床应用。     

帕利哌酮与利司哌酮治疗精神分裂症近期疗效与安全性比较

目的比较帕利哌酮与利司哌酮治疗精神分裂症的近期疗效及安全性。方法 94例精神分裂症患者分为帕利哌酮组与利司哌酮组,每组47例。帕利哌酮组起始剂量3mg·d~(-1),每隔1～2wk增加剂量1次,增幅为每次3mg,剂量稳定在3～12mg·d~(-1);利司哌酮组起始剂量2m·d~(-1),每隔1～3d增加剂量1次,增幅为每次2mg,2wk内加至4～6mg·d~(-1),观察6wk。于基线及wk 2、4、6末,采用阳性和阴性症状量表(PANSS)评定疗效,采用副反应量表(TESS)评定不良反应。结果最终纳入分析的有91例,其中帕利哌酮组47例,利司哌酮组44例。治疗4、6 wk末2组PANSS总分、阳性症状分、阴性症状分和精神病理症状分均显著降低(P<0.05或P<0.01)。wk 6末帕利哌酮组治疗有效率为70%,利司哌酮组为66%,疗效无显著差异(P>0.05)。wk 2末2组间PANSS总分、阳性症状分和精神病理症状分有非常显著差异(P<0.01),阴性症状分无显著差异(P>0.05);wk 4、wk 6末2组间PANSS总分及各分项分均无显著差异(P>0.05)。帕利哌酮组和利司哌酮组不良发应发生率无显著差异(72%vs.80%,P>0.05),帕利哌酮组锥体外系反应发生显著少于利司哌酮组(P<0.01)。结论帕利哌酮治疗精神分裂症的疗效与利司哌酮相当,且起效较快,锥体外系反应发生较少,安全性较好。     

Effects of dopamine D2 receptor Ser311Cys polymorphism and clinical factors on risperidone efficacy for positive and negative symptoms and social function

Risperidone is an atypical antipsychotic agent with efficacy for both positive and negative symptoms of schizophrenia. However, what makes an antipsychotic 'atypical' remains unclear. We recently found that the T102C polymorphism in the 5-HT2A receptor gene could affect risperidone's efficacy for negative symptoms. The present study investigated the effect of the Ser311Cys polymorphism in the dopamine D2 receptor (DRD2) gene on risperidone treatment response. A total of 123 Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. Clinical manifestations were measured bi-weekly with Positive and Negative Syndrome Scale (PANSS) and Nurses' Observation Scale for Inpatients Evaluation (NOSIE, for assessment of social function). For adjusting the within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was utilized to analyse the effects of Ser311Cys polymorphism and other covariates on clinical performance. Compared with patients who had the Ser311Ser genotype, patients with the Ser311Cys genotype had lower scores on PANSS Positive, Negative, General Psychopathology and Cognitive subscales and NOSIE, after adjustment for 5-HT2A T102C polymorphisms and other confounders. The 5-HT2A T102C polymorphism had marginal influences on PANSS Total and Negative subscale scores. Male gender, fewer previous hospitalizations, and higher risperidone dose predicted better treatment response after control for other variables. The preliminary results suggest that variations in the DRD2 gene influence risperidone treatment response for positive, negative, and cognitive symptoms, general psychopathology, and social functioning. Several clinical factors may also contribute to inter-individual differences in risperidone treatment response.     

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。     

阿立哌唑与利培酮治疗稳定期精神分裂症临床疗效评估

目的:通过跟踪随访,比较阿立哌唑与利培酮治疗稳定期精神分裂症的临床疗效及不良反应.方法:用阳性与阴性症状量表(PANSS)、社会功能缺陷筛选量表(SDSS)、日常生活能力量表(ADL)对稳定期精神分裂症患者进行评定.结果:入组时两组药物患者的PANSS各项分值在入组时无显著性差异(P＞0.05),6个月末PANSS减分率无显著性差异(P＞0.05).入组时两组药物患者的SDSS总分和ADL总分均无显著性差异(P＞0.05),6个月末利培酮组患者的ADL总分显著降低(P＞0.05),而阿立哌唑组患者的SDSS总分和ADL总分均显著降低(P＜0.01).药物不良反应方面,利培酮组锥体外系反应及对催乳素水平影响均明显高于阿立哌唑组.结论:对稳定期精神分裂症患者,两种药物对阳性与阴性症状的改善作用相当,但阿立哌唑组更能明显地改善社会功能和日常生活能力.     

Fluvoxamine augmentation in risperidone-resistant schizophrenia: an open trial

We investigated the efficacy and safety of augmenting risperidone with fluvoxamine for the treatment of residual positive and negative symptoms in patients with chronic schizophrenia who had shown an incomplete response to risperidone. A total of 30 patients completed the open trial over a 12-week period during which fluvoxamine was added to risperidone. The result from the positive and negative syndrome scale (PANSS) and Simpson-Angus extrapyramidal effects (S-A) scale were examined at baseline, 1, 2, 4, 8 and 12 weeks of treatment. There were no significant differences in PANSS positive, negative and general psychopathology scores, or in S-A scale scores at any point during the treatment. These results suggest that fluvoxamine appears to be ineffective in augmenting the risperidone treatment response in chronic schizophrenic patients. Further controlled trials will be needed to confirm this observation.