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。     

奥氮平治疗难治性精神分裂症生活质量研究

目的：评价国产奥氮平替代氯氮平对难治性精神分裂症患者的疗效与生活质量的影响。方法：对60例服用氯氮平的难治性精神分裂症患者换用奥氮平治疗12周。采用阳性与阴性症状量表（PANSS）评定疗效，用治疗中出现的症状量表（TESS）评定不良反应，使用健康状况问卷（SF-36）评定患者生活质量。结果：PANSS总分及阴性症状评分在治疗后有显著下降，某些不良反应比替换前明显减少。与治疗前相比较，治疗后生理机能（PF）、生理职能（RP）、生命活力（VT）、情感职能（RE）评分及SF-36总分显著升高。结论：奥氮平对难治性精神分裂症疗效肯定，安全性高，对阴性症状的治疗效果优于氯氮平，能更好改善患者的生活质量。     

Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine

OBJECTIVE: Treatment options are very limited for individuals with schizophrenia resistant to clozapine. We tested the hypothesis that amisulpride augmentation would lead to an improvement in these patients. METHOD: This was an open non-randomized study. Thirty-three patients with sub-optimal response to clozapine were commenced on amisulpride in addition to clozapine. Clinical status was evaluated at baseline, 3 and 6 months using the Positive And Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Global Assessment Scale (GAS), Calgary Depression Scale, Calgary Anxiety Scale and various side effect rating scales. RESULTS: Twenty-eight subjects completed 6 months treatment on clozapine and amisulpride. There was a statistically significant improvement in the mean scores for PANSS, SANS and GAS at follow-up and no significant changes in side effect ratings. CONCLUSION: Co-administration of amisulpride, in a group of patients partially or non-responsive to clozapine, may lead to a substantial improvement in positive and negative symptoms, without worsening the side effect burden.     

Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment

BackgroundSeveral placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results. The aim of this study was to further investigate the efficacy and safety of this augmentation strategy, and its effect on the glutamatergic system through utilizing mismatch negativity (MMN) component of auditory event related potentials.MethodsThe study was designed to evaluate the efficacy and safety of lamotrigine augmentation of clozapine in a 12-week, double-blind, placebo-controlled, prospective, randomized design. Thirty-four patients diagnosed according to DSM-IV schizophrenia criteria and with partial response to clozapine were included. Patients were randomized to 25 mg/day of lamotrigine or placebo, gradually increasing up to 200 mg/day on the 6th week. The change in psychopathology was assessed with Positive and Negative Syndrome (PANSS), Calgary Depression (CDS) and Clinical Global Impression-Severity (CGI-S) scales. A neuropsychological test battery was administered and MMN measurements were also obtained at baseline and endpoint. Safety evaluation included physical examination, UKU Side Effect Rating Scale (UKU) assessment and serum drug level measurements.ResultsNo significant differences were found between the two treatment groups in PANSS Positive and General Psychopathology, CDS, neurocognitive test and UKU scores, as well as MMN measurements. PANSS Total, Negative and CGI-S scores showed significant improvement compared to lamotrigine in the placebo group.ConclusionThis study did not show any benefit of augmentation of clozapine with lamotrigine in schizophrenia patients with partial response. The need for further investigation of other augmentation strategies of clozapine in partially responsive schizophrenia patients is evident.     

奥氮平与氯氮平治疗精神分裂症的比较研究

目的：评价奥氮平治疗精神分裂症的临床疗效与安全性,方法 ８０例精神分裂症患者随机分成２组,分别给予奥氮平与氯氮平治疗１２周,采用ＰＡＮＳＳ评价临床疗效,ＴＥＳＳ评价不良反应。结果：全部病人完成疗程,奥氮平组治疗前后ＰＡＮＳＳ减分率４２．４％,有效率为８２．５％,氯氮平组治疗前后ＰＡＮＳＳ减分率３７．５％,有效率为７０％,未见严重的药物不良反应,安全性好。结论：奥氮平是一种有效的治疗精神分裂症的药物     

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。     

奥氮平和氯氮平治疗精神分裂症老年患者的对照研究

目的：对比奥氮平与氯氮平治疗精神分裂症老年患者的疗效和安全性。方法：对64例精神分裂症老年患者分别给予奥氮平、氯氮平治疗，其中奥氮平组30例，氯氮平组34例，疗程8周。以阳性症状和阴性症状量表(PANSS)、临床疗效总评量表(CGI)、简明精神病评定量表(BPRS)评定临床疗效。以副反应量表(TESS)和实验室监测评价安全性。结果：治疗结束时，两组PANSS和BPRS总分较治疗前显著降低，组间差异无显著性。两组间从治疗第1周起各时点PANSS减分率差异有显著性。临床有效率：奥氮平组76．7％，氯氮平组64．7％，两组相仿。奥氮平组不良反应较氯氮平组少，常见不良反应为胆碱能作用、嗜睡、体重增加和一过性肝酶升高等。结论：奥氮平治疗精神分裂症的疗效与氯氮平相似，某些不良反应较氯氮平轻而少；是一种安全有效、服用方便的新型抗精神病药。     

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.     

Amisulpride versus risperidone in the treatment of depression in patients with schizophrenia: a randomized, open-label, controlled trial

OBJECTIVE: To determine the effectiveness of amisulpride on depression in patients with schizophrenia, in comparison to risperidone. METHOD: In this open-label, 12-week study, patients with stable schizophrenia and a comorbid major or minor depressive episode (DSM-IV) taking risperidone were randomized into a risperidone-continuation group (N = 45) or an amisulpride-switch group (N = 42). The main outcome measures were changes from baseline on the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck Depression Inventory (BDI). Secondary efficacy measures included the Positive and Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning. Safety measures included treatment-emergent adverse events and extrapyramidal symptoms. RESULTS: The mean dose at endpoint was 4.2 mg/day for risperidone and 458.3 mg/day for amisulpride. Improvements in the CDSS and BDI scores were significantly greater in the amisulpride-switch group than in the risperidone-continuation group at weeks 8 and 12, and at the endpoint. The amisulpride-switch group also showed a significantly greater reduction in the score for the PANSS depression/anxiety factor, and the total score from baseline to endpoint. No significant difference was observed between the two groups for treatment-emergent adverse events or change from baseline for extrapyramidal symptoms. CONCLUSION: Switching from risperidone to amisulpride in patients with stable schizophrenia with comorbid depression improved depressive symptoms significantly compared to continuing with risperidone.     

Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.

BACKGROUND: The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest. METHODS: The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the "noninferiority" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total). RESULTS: Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the "noninferiority" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients. CONCLUSIONS: Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.     

奥氮平与氯氮平治疗精神分裂症的对照研究

目的 评价奥氮平治疗精神分裂症的疗效和副作用。方法 将39例精神分裂症患者随机分成2组，分别给予奥氮平与氯氮平治疗8周，采用PANSS．CGI评价临床疗效，TESS评价不良反应。结果 奥氮平组与氯氮平组之间疗效无显著性差异，奥氮平组治疗前后PANSS减分率45．7％，有效率78．90％；氯氮平组治疗前后PANSS减分率44．9％，有效率75．0%；氯氮平组副反应明显高于奥氮平组。结论 奥氯平是一种安全有效的新型抗精神病药。     

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.     

Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia

OBJECTIVE: This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome. METHOD: The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI). RESULTS: SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45). CONCLUSION: Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.     

文拉法辛联合氯氮平治疗精神分裂症阴性症状的疗效

目的 观察文拉法辛缓释片合并氯氮平治疗精神分裂症阴性症状的疗效和不良反应.方法 采用单纯随机化法,将107例精神分裂症患者分为研究组（文拉法辛缓释片＋氯氮平）和对照组（氯氮平＋安慰剂）.于治疗前、治疗第2、4、8周末以阳性和阴性症状量表（PANSS）和阴性症状量表（SANS）评定疗效,于治疗第2、4、8周末以药物副反应量表（TESS）评定不良反应.结果 治疗4、8周末,研究组PANSS总分和阴性因子分与对照组比较,差异有统计学意义（P〈0.05）;研究组SANS总分和部分因子分与对照组比较,差异有统计学意义（P〈0.05）.治疗后第2、4、8周末,研究组TESS评分均明显低于对照组,差异有统计学意义（P〈0.05）.结论 文拉法辛缓释片治疗精神分裂症安全有效,协同氯氮平治疗精神分裂症阴性症状可增加疗效.     

奥氮平与利培酮治疗青少年首发精神分裂症对照研究

目的比较奥氮平与利培酮治疗青少年首发精神分裂症的疗效和安全性。方法对60例青少年期首发精神分裂症患者随机分为两组,分别给予奥氮平与利培酮治疗8周。于治疗前及治疗后1、2、6、8周末进行阳性和阴性症状量表(PANSS)及副反应量表(TESS)评定。结果奥氮平与利培酮总的疗效无显著性差异,均能快速起效,PANSS总分比较治疗第1周与第2周末奥氮平组显著低于利培酮组,利培酮组锥体外系反应显著多于奥氮平组。结论奥氮平与利培酮均是治疗首发青少年精神分裂症安全有效的非典型抗精神病药物,可根据患者的不同情况分别选择。     

Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study

BACKGROUND: When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively. METHOD: The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale. RESULTS: Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005). CONCLUSION: Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.     

An efficacy analysis of olanzapine treatment data in schizophrenia patients with catatonic signs and symptoms

Thirty-five patients suffering from schizophrenia, as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were preselected from 7 clinical trials according to a priori criteria of catatonic signs and symptoms based on 3 Positive and Negative Syndrome Scale (PANSS) items: scores for PANSS item 19 (mannerism and posturing) and either item 4 (excitement) or item 21 (motor retardation) had to exceed or equal 4 at baseline. This particular patient population represents a severely psychotic sample: mean +/- SD PANSS total scores at baseline were 129.26 +/- 19.76. After I week of olanzapine treatment, mean PANSS total score was decreased significantly (-13.14; p < .001), as was mean PANSS total score after 6 weeks of olanzapine treatment (-45.16; p < .001); additionally, the positive subscale, negative subscale, and mood scores improved significantly. A significant improvement in the catatonic signs and symptoms composite score was also observed at week 6 (-4.96; p < .001). The mean +/- SD daily dose of olanzapine was 18.00 +/- 2.89 mg after 6 weeks of treatment. The present data analysis suggests the efficacy of olanzapine in the treatment of severely ill schizophrenic patients with nonspecified catatonic signs and symptoms.     

奥氮平联合氯氮平治疗难治性精神分裂症患者的疗效观察

目的：观察奥氮平联合氯氮平治疗难治性精神分裂症的疗效和不良反应。方法：50例难治性精神分裂症患者随机分为合用药组和单用药组各25例。合用药组给予奥氮平合并小剂量氯氮平治疗,单用药组仅给予奥氮平治疗。疗程12周。采用阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）于治疗前及治疗4、8、12周分别评定疗效和不良反应。结果：治疗后两组PANSS总分、阳性症状及阴性症状分均较治疗前明显降低（P〈0.05或P〈0.01）,以合用药组显著低于单用药组（P〈0.05）。两组不良反应比较差异无统计学意义（P〉0.05）。结论：奥氮平联合氯氮平治疗难治性精神分裂症疗效好,不良反应少且依从性好。     

帕利哌酮缓释片治疗急性精神分裂症疗效及安全性的对照研究

Objective The study was designed to evaluate the efficacy and safety of flexible doses of paliperidone extended-release tablets (paliperidone ER) (3 -12) mg/d comparing with olanzapine (5 -15)mg/d in acute hospitalized patients with schizophrenia. Methods All 288 hospitalized patients with DSM-Ⅳ schizophrenia were randomized into paliperidone ER ( n = 143 ) or olanzapine ( n=145 ) treatment in a 6-week, multicenter, double-blind, parallel-group study. The primary efficacy measure was the total score changes of the Positive and Negative Syndrome Scale (PANSS). Clinical Global Impression (CGI),response rate and Visual Analogue Scale (VAS) were adopted as secondary efficacy measures. Results Both paliperidone ER and olanzapine groups demonstrated a significant improvement in total PANSS score (P<0.001). The PANSS total score in paliperidone ER group was reduced (32.3 ± 17.1) at end point,and olanzapine group (34.1 ± 17.4). There was no statistically significant difference between the two groups (P =0.369) after 6-week treatment. There were no statistical differences between two groups in CGI,response rate and VAS sleep quality assessments by the end of the treatment. The common adverse events were extrapyramidal symptoms, insomnia, constipation and prolactin increasing in paliperidone ER group,and somnolenee, EPS, abnormal liver function and abnormal lipid metabolism in olanzapine group.Conclusion Paliperidone ER and olanzapine are similarly effective in significantly improving the symptoms of inpatient with acute schizophrenia. Paliperidone ER demonstrates a favorable safety profile with fewer somnolence, abnormal liver function and abnormal lipid metabolism comparing with olanzapine.     

A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression

PURPOSE: To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial. PATIENTS: Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables. RESULTS: The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered "much" or "very much" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups. CONCLUSION: Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects .