利培酮合并氯氮平治疗难治性精神分裂症临床观察

目的 了解利培酮合并氯氮平治疗难治性精神分裂症的疗效和安全性。方法 对符合CCMD-3精神分裂症诊断标准及难治性标准，分别单用氯氮平与利培酮治疗超过6个月而无效的32例病人，给予两药合并治疗，在治疗后第4，8，12周采用简明精神病量表（BPRS）评分，用t检验分析联合用药前及用药后第4，8，12周BPRS减分率。结果 合并治疗12周后有效率75%，治疗中无因明显副作用而中止治疗者。结论 两药合并治疗难治性精神分裂症不失为一种有效的治疗方法。     

利培酮联合氯氮平治疗难治性精神分裂症临床研究

目的探讨利培酮联合氯氮平治疗难治性精神分裂症的疗效及安全性。方法对40例难治性精神分裂症患者,给予利培酮联合氯氮平治疗8周、12周。采用阳性与阴性症状量表、副反应量表评定临床疗效及不良反应。结果利培酮联合氯氮平治疗难治性精神分裂症的显效率为42.5%,有效率为57.5%。有效剂量利培酮为1mg~4mg/d,氯氮平为100mg~350mg/d,不良反应轻微且发生率低,均可耐受,经对症处理后均可缓解或消失。结论利培酮联合氯氮平治疗难治性精神分裂症疗效显著,安全性高,依从性好,可作为难治性精神分裂症的治疗方法。     

利培酮合并氯氮平治疗难治性精神分裂症

目的：了解利培酮与氯氮平合并治疗难治性精神分裂症的疗效与副反应。方法：两药合用治疗难治性精神分裂症患者68例共12周，以阳性症状与阴性症状量表（PANSS）等评定其临床疗效及副反应。结果：疗后PANSS总分及分量表评分均显著下降，有效率为76.5%，副反应较轻。结论：利培酮与氯氮平可合并治疗难治性精神分裂症。     

利培酮和氯氮平治疗难治性精神分裂症对照观察

目的　了解利培酮和氯氮平对难治性精神分裂症患者疗效。方法　对１３５ 例难治性精神分裂症患者按ＣＣＭＤⅡＲ 标准确诊后,随机分成两组,用利培酮和氯氮平各治疗６ 个月,在治疗前及治疗后２ 、４、６ 个月用ＢＰＲＳ、ＳＡＮＳ、ＳＤＳＳ、ＣＧＩ量表评定疗效。结果　在治疗难治性精神分裂症利培酮有效率３５－３ ％ ,氯氮平有效率３１－３％ ,量表显示二药对难治性精神分裂症疗效相似,利培酮主要以不良反应为轻度静坐不能,震颤,急性肌张力障碍,氯氮平为嗜睡,头晕,恶心,呕吐,流涎。结论　传统的神经阻滞剂治疗难治性精神分裂症无效时,非典型抗精神病药尤其利培酮可作为理想的药物。     

利培酮和氯氮平治疗伴抑郁症状的难治性精神分裂症对照研究

目的：比较利培酮和氯氮平对伴抑郁症状的难治性精神分裂症疗效。方法：共70例难治性精神分裂症患者随机服用利培酮和氯氮平治疗。利培酮组34例,氯氮平组36例;伴有抑郁症状者39例,利培酮组17例,氯氮平组22例。治疗12周。分别于治疗前、治疗4、8、12周末采用阳性与阴性症状量表（PANSS）,汉密尔顿抑郁量表（HAMD）及功能大体评定量表（GAF）评定疗效。结果：两组PANSS、HAMD和GAF评分在治疗12周均有显著改善;两组间比较差异无显著性。有、无抑郁症状组在治疗4、8、12周末的HAMD总分与治疗前比较均显著减少。结论：抑郁症状不影响难治性精神分裂症的疗效;利培酮和氯氮平对伴抑郁症状的难治性精神分裂症均有效。     

氯氮平合并利培酮治疗难治性精神分裂症观察

目的：观察氯氮平合并利培酮治疗难治性精神分裂症的疗效和安全性。方法：对30例难治性精神分裂症患者给予氯氮平合并利培酮治疗，疗效8周，治疗前和治疗后进行阳性与阴性症状量表（PANSS）评定疗效和不良反应量表（TESS）评定副作用。结果：治疗8周后总有效率为66.7％，治疗前后PANSS总分及各分量表分均有显著差异。常见副作用是锥体外系症状（EPS），但程度较轻。结论：两药合并治疗难治性精神分裂症是一种有效的治疗方法，安全性高，耐受性及依从性好。     

氯氮平合并利培酮与氯氮平合并舒必利治疗难治性精神分裂症的对照研究

目的：研究对比氯氮平合并利培酮与氯氮平合并舒必利治疗难治性精神分裂症的疗效和安全性。方法：把住院的60例难治性精神分裂症患者，随机分为A，B两组，A组应用氯 平合并利培酮治疗，B组应用氯氮平合并舒必利治疗，观察8周，分别在治疗前与治疗后用阳性与阴性症状量表（PANSS）和不良反应症状量表（TESS）评定。结果：A组治疗8周后总有效率为70％，B组治疗8周后总有效率为63．3％，两组间疗效无显著差异（P＞0．05），TESS总分两组间有显著差异（P＜0．05），B组副反应大。结论：对难治性精神分裂症病人，氯氮平合并利培酮与氯氮平合并舒必利治疗均取得了较好的效果，A组副反应轻。     

利培酮与氯氮平治疗难治性精神分裂症对照研究

目的 比较利培酮与氯氮平治疗难治性精神分裂症的疗效和副反应。方法 将符合入组条件的病人随机分为2组,分别服用利培酮和氯氮平治疗12周,用PANSS和TESS评定疗效和副反应情况。结果 利培酮组总有效率为62.9％,氯氮平组为60.0％,经统计学处理无显著性差异(P>0.05)。结论 利培酮对难治性精神分裂症的疗效与氯氮平相当,副作用轻,易被病人接受。     

氯氮平合并利培酮与氯氮平治疗精神分裂症阴性症状的对照研究

目的 比较氯氮平合并利培酮与氯氮平对精神分裂症阴性症状的疗效。方法 60例长期住院的精神分裂症患者,分别接受氯氮平合并利培酮和氯氮平治疗,疗程8周,用BPRS,SANS,SAPS,TESS评定疗效和副反应。结果 氯氮平合并利培酮组在治疗后4周、8周SANS评分较治疗前均有显著差异(P<0.01);氯氮平组在治疗后8周SANS评分与治疗前比较也有显著差异(P<0.05)。两组在治疗后4周、8周时,SANS减分均数比较有显著差异(P<0.01)。结论 氯氮平合并利培酮与氯氮平对治疗精神分裂症阴性症状均有一定效果,且氯氮平合并利培酮对阴性症状的改善优于单用氯氮平,起效时间快。     

奥氮平合并氯氮平对男性难治性精神分裂症阴性症状的疗效及安全性的研究

目的观察奥氮平合并氯氮平治疗男性以阴性症状为主的难治性精神分裂症的疗效以及安全性。方法对43例男性原服用氯氮平且以阴性症状为主的难治性精神分裂症患者合并奥氮平5～20mg／d治疗8周,同时于2周内将氯氮平减量且氯氮平剂量2周后不再变化,并于合并治疗前及后2周、4周、8周评定阳性症状与阴性症状量表（PANSS）、副反应量表（TESS）。结果合并奥氮平治疗后2周、4周、8周末PANSS总分和TESS评分较合并前有明显差异。结论奥氮平合并氯氮平对于男性难治性精神分裂症患者的阴性症状有明显的改善,副反应也有减少。     

Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial

RATIONALE: Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. OBJECTIVES: To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. METHODS: We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. RESULTS: Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047). CONCLUSIONS: Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.     

Comparative efficacy of risperidone and clozapine in the treatment of patients with refractory schizophrenia or schizoaffective disorder: a retrospective analysis

BACKGROUND: Clozapine is effective in up to 60% of patients with refractory schizophrenia, whereas the efficacy of risperidone remains unknown. This retrospective study examined the relative efficacy of these drugs in chronically institutionalized patients refractory to conventional antipsychotic agents. METHOD: A total of 24 patients who at different time periods had received adequate trials of both clozapine and risperidone and met our inclusion criteria for minimum dose and duration of each trial were included; for clozapine, a minimum dose of 300 mg/day had to be maintained for at least 12 weeks, and for risperidone, a minimum dose of 6 mg/day for at least 6 weeks. Information obtained from systematic retrospective chart review was blindly rated by 2 psychiatrists using the 7-point Clinical Global Impressions-Improvement (CGI-I) scale on overall clinical state and along specific symptom domains of positive symptoms, negative symptoms, and aggressive behavior. RESULTS: The mean +/- SD dose was 520+/-94 mg/day for clozapine and 7.5+/-2.2 mg/day for risperidone. Fourteen patients (58%) were classified as responders to clozapine, while 6 (25%) responded to risperidone (CGI-I score of 1 or 2); on specific symptom domains, response rates to clozapine were 38% (9/24) on positive symptoms, 29% (7/24) on negative symptoms, and 71% (12/17) on aggressive behavior. For risperidone, response rates were 17% (4/24) on positive symptoms, 8% (2/24) on negative symptoms, and 41% (7/17) on aggressive behavior. CONCLUSION: The results of this study support the utility of first giving a risperidone trial in a treatment algorithm for refractory patients because of its better risk/benefit profile compared with clozapine. Clozapine, however, remains our gold standard in the management of these patients.     

Effect of topiramate on plasma concentrations of clozapine, olanzapine, risperidone, and quetiapine in patients with psychotic disorders

OBJECTIVES: To investigate the effect of topiramate on the steady-state plasma concentrations of the second-generation antipsychotics--clozapine, olanzapine, risperidone, and quetiapine--in patients with schizophrenia or bipolar disorder. METHODS: Thirty-eight outpatients on long-term treatment with clozapine (250-500 mg/d, n = 10), olanzapine (10-20 mg/d, n = 12), risperidone (3-6 mg/d, n = 9), or quetiapine (200-600 mg/d, n = 7) received adjunctive topiramate, gradually titrated up to a final dosage of 200 mg/d for 6 weeks. Pharmacokinetic assessments were made at baseline and at the end of treatment weeks 4 and 8 at topiramate dosages of 100 and 200 mg/d, respectively. RESULTS: Plasma concentrations of clozapine and its metabolite (norclozapine), olanzapine, risperidone and its metabolite (9-hydroxy-risperidone), and quetiapine were not significantly modified during concomitant administration of topiramate. Adjunctive topiramate therapy was well tolerated in all groups. CONCLUSIONS: These findings indicate that topiramate, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of the new antipsychotics-clozapine, olanzapine, risperidone, and quetiapine.     

Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. METHOD: In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. RESULTS: From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. CONCLUSIONS: In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.     

氯氮平合并利培酮治疗难治性精神分裂症

目的：了解氯氮平全早培酮的治疗难治性精神分裂症的疗效和安全性。方法：２６例符合ＣＣＭＤ－２－Ｒ精神分裂症诊断标准且临床判断属于难治性病人,予氯氮平合并利培酮治疗,疗程８周,分别在治疗前及治疗后进行阳性与阴性症状量表（ＰＡＮＳＳ）和不良瓜症状量表（ＴＥＳＳ）评定。结果：合并治疗８周后部是性,阴性及一般精神病理分治疗前后均有显著差异。ＴＥＳＳＵ叫分治疗前后无显著差异。副反应主要为静坐不能,肌张力增高,     

低剂量氯氮平维持治疗稳定期精神分裂症5年的随访对照研究

目的探讨伊剖量氯氮平对稳定期精神分裂症维持治疗的临床疗效及安全性。方法对1141例稳定期精神分裂症患者随访5年（氯氮平组351例,剂量上限为250mg／d,对照组分别为氯丙嗪组260例、奥氮平组170例和利培酮组360例）：用阳性与阴性综合征量表（PANSS）、临床疗效总评量表病情严重程度项目（CCI—SI）、WHO／残疾评价量表一简化版（DAS—S）、副反应量表（TESS）、心电图、生化检验等评估疗效和不良反应。维持治疗期间要求单一用药,如出现脱落、换药、合并其他抗精神病药物者,作为中断治疗。随访时间5年。结果依据CGI—SI评分,氯氮平组症状恶化例次最低（7．4％）,低于氯丙嗪组（16．9％）、奥氮平组（8．8％）以及利培酮组（14．2％）。研究终点中断率由高到低的单药治疗依次为：奥氮平、氯丙嗪、利培酮、氯氮平。根据Cox模型回归分析的回归系数和相对危险度的估计值判断,影响氯氮平维持时间由短到长的因素依次为：PANSS中的兴奋、概念紊乱,TESS中的困倦、流涎以及心电图异常。结论低剂量氯氮平对稳定期精神分裂症长期维持治疗具有良好的疗效。     

Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics

OBJECTIVE: Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics. METHOD: Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone. RESULTS: Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31). CONCLUSIONS: Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.     

Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis

BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center.Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapineolanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine相似文献   

Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study

1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments.