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.     

A comparison of two doses of melperone,an atypical antipsychotic drug,in the treatment of schizophrenia

Melperone at a dose of 300 mg/day has been reported to be as effective as thiothixene and superior to placebo in the treatment of schizophrenia. Limited ability to cause extrapyramidal side effects (EPS) and absence of an effect on plasma prolactin (pPRL) levels suggests that it is an atypical antipsychotic drug. The goal of this pilot study was to determine: (1). the ability of melperone 400 mg/day to produce greater improvement in psychopathology than melperone 100 mg/day; and (2). to compare side effects of these two doses of melperone. Melperone, 100 or 400 mg/day, was administered to 34 acutely hospitalized patients with schizophrenia for 6 weeks in a randomized, double-blind manner. Psychopathology, EPS, pPRL levels, and body mass index (BMI) were evaluated at baseline and 6 weeks. Twenty-seven completed the 6-week treatment. A last carried forward analysis revealed no significant difference in the ability of the two doses of melperone to improve psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS)-Total and Positive subscale, the Scale for the Assessment of Negative Symptoms (SANS), the Schedule for Affective Disorders and Schizophrenia-Disorganization subscale, and the Global Assessment Scale (GAS). Treatment with melperone was not associated with exacerbation of EPS, or an increase in pPRL levels or BMI. The Abnormal Involuntary Movement Scale (AIMS) was not significantly changed by treatment with melperone. These results suggest that melperone was equally effective at doses 100 and 400 mg/day, for ameliorating psychopathology and improving overall psychiatric status in patients with schizophrenia. However, the lack of difference and a placebo control group, as well as modest degrees of change in psychopathology, require caution about assuming efficacy of either dose. The lack of significant side effects such as exacerbation of EPS, pPRL elevation, and weight gain indicates melperone is well tolerated.     

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.     

The sensitivity of quality-of-life scale WHOQOL-100 to psychopathological measures in schizophrenia

We aimed to investigate the reliability and the clinical sensitivity of the World Health Organization Quality of Life (WHOQOL-100) scale for patients diagnosed with schizophrenia because of its multilingual, multidimensional, and cross-cultural properties. Fifty-four stabilized outpatients with schizophrenia and 49 age-, sex-, and occupation-matched healthy control subjects were recruited. The scale showed high internal consistency (Cronbach alpha = 0.94). While there was no correlation between total scores of psychopathology measures (Brief Psychiatric Rating Scale [BPRS], Scale for the assessment of Negative Symptoms [SANS], Scale for the Assessment of Positive Symptoms [SAPS], and Clinical Global Impression [CGI]), significant negative correlations were obtained especially between subscales of the BPRS, SANS, SAPS, and QOL domains. Stepwise multiple regression analysis also revealed that the BPRS anxiety/depression and SANS anhedonia subcales were the predictor variables in five of six QOL domains in the schizophrenia group. The better quality-of-life scores of the mild group on physical and psychological domains indicate that the WHOQOL-100 could be used as an outcome measure in clinical studies. Thus, the WHOQOL-100 scale is a reliable, subjective quality-of-life scale for patients diagnosed with schizophrenia. The clinical sensitivity should also be assessed in large follow-up studies.     

Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics

The primary aim of our study is to evaluate the level of insight during the switch from a classical antipsychotic drug to a atypical neuroleptic. Twenty-two schizophrenic patients were admitted to the study, 9 were male and 13 were female. Standardized questionnaire were: Scale for Assessment of Negative Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessing the three components of Insight (SAI). All patients were receiving haloperidol at time of recruitment. Eight patients were switched to clozapine, 3 to risperidone and 11 to olanzapine. The global function, measured with BPRS, increased after administration of atypical antipsychotics. The positive and negative symptoms were reduced. The level of insight was increased after the administration of the atypical antipsychotics. The cognitive effect of the atypical antipsychotics changed the level of insight and augmented the compliance.     

Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome

OBJECTIVE: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other measures in an effort to find predictors of response to clozapine in our early-onset treatment-refractory population. METHOD: Fifty-four children and adolescents participated in double-blind (n = 22) or open-label (n = 32) clozapine trials. Clinical evaluations took place at baseline, week 6 on clozapine, and at 2- to 6-year follow-up. The data were analyzed in relation to demographics, age at onset, IQ, clozapine dose, and plasma concentrations of prolactin, clozapine, NDMC, and NDMC/clozapine ratio. Stepwise regression and correlation analyses were performed to find predictors of treatment response. RESULTS: Clinical improvement after 6 weeks of clozapine treatment, as measured by the percentage of improvement on the Brief Psychiatric Rating Scale and the Scale for the Assessment of Positive Symptoms, was strongly associated with the NDMC/clozapine ratio at the 6-week time point (Pearson correlation coefficient: r = 0.41; p < .01 for Brief Psychiatric Rating Scale and r = 0.43; p < .01 for Scale for the Assessment of Positive Symptoms). Although the rate of side effects was higher than that typically found in the adult population, it did not appear to be related to clozapine dose, clozapine or NDMC plasma concentrations, or NDMC/clozapine ratio. Outcome at long-term follow-up, as measured by Children's Global Assessment Scale, was associated with lesser illness severity at baseline and with greater improvement during the initial 6 weeks of clozapine treatment. CONCLUSIONS: The NDMC/clozapine ratio may be a valuable predictor of response to clozapine and may suggest new approaches to clozapine treatment.     

左旋千金藤啶碱与氯氮平治疗精神分裂症双盲对照研究

目的：探讨中药提取物左旋千金藤啶碱（L－SPD）对精神分裂症的治疗效果及副作用。方法：采用双盲，双模拟，氯氮平对照，随机入组方法，实验期六周，疗效评定采用简明精神病评定量表（BPRS），阳性症状量表（SAPS），阴性症状量表（SANS）及四级临床疗效评定标准，不良反应采用副作用量表（TESS）评定。结果：左旋千金藤啶碱与氯 平治疗精神分裂症总体疗效相当，均明显地消除阴，阳性症状（P＞0．05），千金藤副作用明显少于氯氮平治疗精神分裂症总体疗效相当，均能明显地消除阴，阳性症状（P＞0．05），千金藤副作用明显少于氯氮平（P＜0．05），结论：左旋千金藤啶碱对精神分裂症有显著疗效，且副作用更少。     

Preliminary results from an Australian psychosocial rehabilitation program for people with serious mental illness

Psychosocial rehabilitation, for those with a serious mental illness, is of significant importance due to both its frequency and cost to government. This paper describes the implementation and preliminary assessments of a new psychosocial rehabilitation program in New South Wales. Of particular urgency was the requirement to establish baseline measures for ongoing service evaluation at the unit. An extensive array of assessment tools (Brief Psychiatric Rating Scale, BPRS; Scale for the Assessment of Negative Symptoms, SANS; Quality Of Life Scale, QOLS) was applied to determine the functioning of clients prior to the program. Following the initial assessments, subsequent measures were undertaken on completion of the program and then at 1 year follow-up. It was hypothesized that the clients would demonstrate significant improvements on these measures with a reduction in their psychopathology as assessed by the BPRS, improvement in their quality-of-life as measured by the QOLS and improvement in their negative symptoms as measured by the SANS. The final outcome demonstrated improvement in the assessment scores by 34%. A positive correlation to the above results showed a 54% reduction in the re-admission rate of clients and length of stay in hospital. The paper describes further developments regarding this psychosocial rehabilitation unit and suggests other psychosocial rehabilitation initiatives.     

Relations between movement disorders and psychopathology under predominantly atypical antipsychotic treatment in adolescent patients with schizophrenia

Objective To examine relations between movement disorders (MD) and psychopathological symptoms in an adolescent population with schizophrenia under treatment with predominantly atypical antipsychotics. Method MD symptoms and psychopathology were cross-sectionally assessed in 93 patients (aged 19.6 ± 2.2 years) using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS), Brief Psychiatric Rating Scale (BPRS) and the Schedule for Assessment of Negative/Positive Symptoms (SANS/SAPS). Results All patients with MD symptoms (n = 37; 39.8 %) showed pronounced global psychpathological signs (SANS/SAPS, BPRS: p = 0.026, p = 0.033, p = 0.001) with predominant anergia symptoms (p = 0.005) and inclinations toward higher anxiety- and depression-related symptoms (p = 0.051) as well as increased thought disturbance (p = 0.066). Both negative symptoms and anergia showed trends for positive correlations with tardive dyskinesia (p = 0.068; p = 0.065) as well as significant correlations with parkinsonism symptoms (p = 0.036; p = 0.023). Akathisia symptoms correlated significantly with hostile and suspicious symptoms (p = 0.013). A superfactor-analysis revealed four factors supporting the aforementioned results. Conclusion MD symptoms and psychopathology are in some respects related to each other. Motor symptoms representing on the one hand trait characteristics of schizophrenia might additionally be triggered by antipsychotics and finally co-occur with more residual symptoms within a long-term treatment.     

A 1-year open-label trial of olanzapine in school-age children with schizophrenia

OBJECTIVE: To determine the response of children with childhood-onset schizophrenia to a 1-year prospective, open-label trial of olanzapine. METHODS: Twenty children (age range 6-15 years) with childhood-onset Diagnostic and Statistical Manual of Mental Disorders (fourth edition) schizophrenia participated. The treating clinician was free to vary or discontinue dosing and use additional medications. Symptoms were assessed by the Brief Psychiatric Rating Scale-Child version (BPRS-C), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms. Extrapyramidal symptoms, akathisia, temperature, and weight were monitored. RESULTS: BPRS-C subscales of thought disturbance and psychomotor excitation, and the Scale for the Assessment of Positive Symptoms demonstrated significant decreases by 6 weeks of treatment; BPRS-C anxiety and the Scale for the Assessment of Negative Symptoms (SANS) showed significant improvement after 1 year of treatment. Seventy-four percent of subjects were considered treatment responders, with a greater than 20% reduction in total BPRS-C score and overall impairment of mild or better. Weight gain (body mass index) was above that expected for normal development in every child. No child developed neuroleptic-related dyskinesias. Seventy-four percent (n = 14) of patients completed this 1-year, open-label trial. Of the 5 subjects who discontinued, weight gain was noted as the reason for 4 subjects. CONCLUSIONS: Olanzapine appears useful in the treatment of childhood-onset schizophrenia, although there may be a delayed onset of benefit for anxiety and negative symptoms. Weight gain is problematic, but the emergence of dyskinesias may be rare. Additional controlled trials are indicated.     

Melperone in the treatment of neuroleptic-resistant schizophrenia

Melperone is an effective antipsychotic drug that has been reported to have atypical properties, i.e. low extrapyramidal side effect liability at clinically effective doses. It also does not increase serum prolactin levels. Its effectiveness for patients with neuroleptic (treatment)-resistant schizophrenia has not been evaluated. In this study, melperone was administered, in an open trial design of 6 weeks' duration, to 44 patients with chronic neuroleptic-resistant schizophrenia. The Global Assessment Scale (GAS), Brief Psychiatric Rating Scale (BPRS) and measures of extrapyramidal symptoms and other clinical variables were assessed at baseline and 6 weeks. Thirty-seven patients completed the 6-week trial. Melperone significantly improved overall psychiatric status as measured by GAS score for all evaluable subjects [last value carried forward (LVCF) and a completers analysis]. No significant effects on BPRS measures of psychopathology scores were found in the LVCF or completers analysis. Patients who showed > or = 20% decrease in the BPRS Total score (N=7) were more likely to have high baseline psychopathology, as measured by BPRS Total and Anxiety-Depression subscales, than those who showed > or = 20% increase in the BPRS Total score (N=8). Non-responders to melperone generally did not respond to subsequent treatment with clozapine, indicating that this group of patients was very treatment resistant. Melperone was not associated with worsening of extrapyramidal symptoms, elevation in plasma prolactin levels, or an increase in body mass index (BMI). The results suggest that a proportion of neuroleptic-resistant patients with schizophrenia respond to melperone, which requires further controlled study.     

Stability of positive and negative symptom constructs during neuroleptic treatment in schizophrenia.

To assess the structural stability of positive and negative symptom ratings, we rated 40 schizophrenic inpatients on the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS) at medication-free baseline and after 4 weeks of neuroleptic treatment. Positive symptom variables consisted of six BPRS items, and the negative symptom variables consisted of the five SANS subscale global scores. On principal components analysis, a three-factor, oblique-rotated solution resulted, with a negative symptom factor, a positive symptom factor, and an unstable behavioral agitation factor. The pre- and posttreatment factor loading patterns were similar. The findings suggest that BPRS-positive symptom items and the SANS measure distinct clinical dimensions and that the construct is stable, as demonstrated by minimal structural change with time.     

氯氮平治疗首发精神分裂症临床效应影响因素的筛选和评估

为筛选与氯氮平治疗效应相关的影响因素、指导临床合理选药，对３０例首发精神分裂症氯氮平治疗效应的影响因素进行筛选与评估。入组患者均按规定剂量给药，选用简明精神病评定量表（ＢＰＲＳ）、阴性症状评定量表（ＳＡＮＳ）、总体功能评定量表进行临床评定，动态观察治疗前及治疗后第１，２，４，８，１２周的病情变化，同时作血药浓度、催乳素和治疗前威斯康辛卡片分类测验（ＷＣＳＴ）测查。结果显示，治疗前ＢＰＲＳ的思维障碍因子分及激活性增高因子分高、基础催乳素水平低、首发年龄大、ＷＣＳＴ的保存记忆反应数多而完成第一套范畴数少、ＳＡＮＳ的注意障碍因子分高而思维贫乏因子分低等８项指标，对氯氮平治疗１２周时的疗效有正性影响。提示在首发精神分裂症的治疗中，可根据这８项影响因素合理选用氯氮平     

Clozapine-induced weight gain: prevalence and clinical relevance.

OBJECTIVE: The aim of this study was to determine the prevalence and clinical relevance of weight gain during clozapine treatment. Previous reports indicated clinically significant weight gain in 13% to 85% of patients and an average gain of 9.0 to 24.7 lb. METHOD: Twenty-one state hospital patients with treatment-resistant schizophrenia or schizoaffective disorder were weighed weekly for 12 weeks before clozapine treatment and during the first 16 weeks of treatment. Psychiatric symptoms were rated with a modified version of the Brief Psychiatric Rating Scale (BPRS). RESULTS: The mean weight gain for the entire group was 13.9 lb, or 8.9% of body weight. During the 16 weeks of clozapine treatment, 38% of the patients experienced marked weight gains and 29% had moderate weight gains. The improvements in BPRS total score and composite negative symptom score were significantly greater for the eight patients with marked weight gains than for the other 13 patients. CONCLUSIONS: Clozapine's propensity to induce weight gain may relate to the drug's efficacy and/or its unique neuropharmacologic effects. Increased attention to this phenomenon is important because of the morbidity associated with obesity.     

The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy

INTRODUCTION: Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine. DATA SOURCES/STUDY SELECTION: A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score. RESULTS: The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis). CONCLUSION: This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.     

Effect of clozapine on serum leptin,insulin levels,and body weight and composition in patients with schizophrenia

OBJECTIVE: Weight gain frequently occurs during treatment with clozapine. However, the pathophysiology of clozapine-induced weight gain remains unclear. The aim of this study was to investigate the influence of clozapine on hormones leptin and insulin in relation to body weight and composition measures to determine their contribution to clozapine-induced weight gain. METHOD: Data are reported on 19 patients with schizophrenia (11 women and 8 men) who completed 10 weeks of treatment with clozapine. Insulin levels, weight measurements, body mass index (BMI), and body composition measurements were evaluated at baseline and at the end of treatment. Leptin levels were assessed at baseline and after 4 and 10 weeks of treatment. Analysis of variance with repeated measures was used to evaluate changes in weight, body composition measures, leptin, and insulin. The Pearson correlations were used to assess the relationships between changes in hormone levels and weight along with body composition measurements. The correlations of change in Positive and Negative Syndrome Scale (PANSS) score with changes in hormone levels, weight gain and body composition measures were evaluated with Pearson correlations. RESULTS: Leptin and insulin levels did not show any significant alterations across time. The use of clozapine was associated with significant increases in BMI (F=19.8, P<.001), lean muscle mass (F=8.2, P=.01), and fat mass (F=15.4, P=.001), while total body fluid percentage (F=4.1, P=.05) significantly decreased. Improvement in PANSS scores was not correlated to change in leptin, insulin, weight, BMI, or body composition measurements. The change in leptin levels was correlated to change in body fat mass. CONCLUSION: The role of leptin in weight gain induced by clozapine might be a regulatory mechanism rather than being etiologic.     

Prefrontal sulcal prominence is inversely related to response to clozapine in schizophrenia

The object of this study was to determine if brain computed tomography (CT) scan measures are related to treatment response to clozapine, an atypical antipsychotic drug that is effective in some therapy-resistant schizophrenic patients. Thirty-four therapy-resistant patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) before and after 6 weeks of treatment with clozapine. The patients were classified into Nonresponders, Moderate Responders, and Good Responders based on the percent change in BPRS. Comparison of these groups on prefrontal sulcal prominence (PSP) indicated a statistically significant linear trend, with nonresponders having the highest, moderate responders an intermediate degree, and good responders the least PSP. There were no linear trends for the ventricular-brain ratio (VBR), and no quadratic trends for either brain measure. A similar linear trend relating PSP to four of five BPRS subscales, including both positive and negative symptoms, was observed. The relationship between PSP and treatment response was also assessed with multiple linear regression, and PSP significantly contributed to prediction of BPRS at 6 weeks. The results are discussed with regards to the hypothesis that the effect of clozapine on psychopathology depends on prefrontal cortical function.     

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.     

哌泊噻嗪、氟哌啶醇癸酸酯与氟奋乃静癸酸酯治疗精神分裂症的对照研究

建桐翁正【摘要】目的验证和比较哌泊噻嗪、氟哌啶醇癸酸酯、氟奋乃静癸酸酯三种长效抗精神病制剂对精神分裂症的疗效及副反应。方法采用多中心、开放随机对照研究，以简明精神病评定量表（ＢＰＲＳ）、阳性症状评定量表（ＳＡＰＳ）、阴性症状评定量表（ＳＡＮＳ）、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（ＲＳＥＳＥ）综合评定。结果治疗后哌泊噻嗪组患者的ＣＧＩＳＩ与ＣＧＩＧＩ分值和ＳＡＮＳ量表总分均低于其它两组，差异均有显著性（Ｐ＜０．０５），而ＢＰＲＳ和ＳＡＰＳ量表总分治疗结束时三组间差异无显著性（Ｐ＞０．０５）。ＴＥＳＳ总分和ＲＳＥＳＥ总分在整个治疗过程中均以氟奋乃静癸酸酯组最高，哌泊噻嗪组最低。结论三组中以哌泊噻嗪对精神分裂症的疗效较好，对阴性症状的改善优于氟哌啶醇癸酸酯组和氟奋乃静癸酸酯组，对阳性症状的疗效近似。哌泊噻嗪组副反应较少，安全度较好     

Clozapine in treatment-resistant patients with schizophrenia,schizoaffective disorder,or psychotic bipolar disorder: a naturalistic 48-month follow-up study

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. METHOD: 101 patients with a DSM-III-R diagnosis of schizophrenia (N = 34); schizoaffective disorder, bipolar type (N = 30); or bipolar disorder with psychotic features (N = 37) were naturalistically treated with clozapine at flexible doses over a 48-month period. Data were collected from 1994 to 2000. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness scale total predicted scores over time were estimated with random-effects regression models. Time to response to clozapine, defined as 50% reduction of BPRS score, was analyzed in the 3 diagnostic groups using the Kaplan-Meier method. Survival curves were compared using the log-rank test. RESULTS: The BPRS total predicted score halved its baseline value in 3 months for bipolar disorder patients, in 6 months for schizoaffective disorder patients, and in 24 months for schizophrenia patients. The proportion of subjects who satisfied the criterion for response to clozapine after 48 months of follow-up was significantly (p <.01) higher in the schizoaffective and bipolar disorder groups (90.0% and 83.8%, respectively) than in the schizophrenia group (64.7%). Baseline scores on the Global Assessment of Functioning (GAF) showed low levels of psychosocial and occupational functioning in all 3 groups. After 48 months of treatment, GAF scores showed a functional improvement in all 3 groups, with significantly (p <.01) greater improvement in the bipolar disorder group compared with the other groups. CONCLUSION: The findings of this study confirm the efficacy and safety of clozapine for treatment-resistant patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Patients with schizoaffective disorder and those with bipolar disorder show greater clinical improvement than those with schizophrenia. Patients with bipolar disorder have the shortest time to response and the highest psychosocial and occupational functioning levels. Patients with schizoaffective disorder have the lowest treatment discontinuation rate.