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

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,     

Changes in serum lipids, independent of weight, are associated with changes in symptoms during long-term clozapine treatment

OBJECTIVE: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. METHODS: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. RESULTS: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. CONCLUSION: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.     

Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia.

OBJECTIVE: This study compared the specific antiaggressive effects of clozapine with those of olanzapine, risperidone, and haloperidol. METHODS: A total of 157 inpatients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were randomly assigned to receive clozapine, olanzapine, risperidone, or haloperidol in a double-blind 14-week trial. The trial was divided into two periods: eight weeks during which the dosage was escalated and then fixed, and six weeks during which variable dosages were used. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the items that reflect positive symptoms of schizophrenia (delusions, suspiciousness or feelings of persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinations) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Patients differed in their treatment response as measured by the hostility item of the PANSS. The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone. The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking, a formal thought disorder, or hallucinations and independent of sedation as measured by the NOSIE. Neither risperidone nor olanzapine showed superiority to haloperidol. CONCLUSION: Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent.     

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.     

Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation

OBJECTIVE: Clozapine and risperidone were the first two antipsychotic drugs of a new class of agents for the pharmacotherapy of schizophrenia. It has been suggested that refractory schizophrenic patients who fail to respond to neither clozapine nor risperidone may respond to a combination/augmentation strategy of both medicaments. METHOD: Three cases of individuals with unremittent schizophrenia treated via this combination are presented. Response was evaluated by clinical follow-up and PANSS rating scale. RESULTS: Good clinical results with no noticeable adverse side effects, ascertained by a reduction from baseline scores of the Positive and Negative Syndrome Scale (PANSS) were obtained in all three patients. CONCLUSION: The findings from this pilot study suggest this combination as a possible therapeutic approach for treating resistant schizophrenic patients.     

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.     

Atypical neuroleptics and selective attention]

GOALS: The aim of this study was to examine selective attention in patients with chronic and refractory schizophrenia who had been exposed for six months to atypical neuroleptic medications: risperidone or clozapine. METHOD: 17 patients satisfying DSM III-R criteria for schizophrenia were assessed according to BPRS and PANSS and abnormal involuntary movements to ESRS. Selective attention tasks were performed before treatment with risperidone or clozapine and at two times during the treatment (6 weeks, T1, and 24 weeks, T2). Patients' performance data were compared to data from a group of general population at T1. Selective attention refers to the ability to discriminate relevant information from irrelevant one. This was measured by a visual search task. Subjects had to search for a target specified by a conjunction of features (color and shape). The target was a black X, while the distracters were white X's, black O's and white O's. The stimuli were displayed on a Macintosh SE computer. A two-button response box was used for response production and the experiment was run in a dimly lit room. A white-fixation stimulus was shown at the center of the display screen between trials. The number of stimuli displayed on a single trial was 1, 4, 7 or 10. The median RTs and error rates of subjects were computed for each factor (target presence and number of stimuli). RESULTS: A Group X Number of items X Presence of target ANOVA applied on median correct RTs revealed a significant Group X Presence interaction [F(1,176) = 60.433, p < .0001]. Performances improved with the time (F2, p < .01). Correlations were found between positive score on PANSS and performance on selective attention (r39 = -.391). CONCLUSION: Atypical neuroleptic do not have a deleterious effect on selective attention but a favorable effect on the schizophrenic patients' performance.     

利培酮、氯氮平维持治疗精神分裂症患者生活质量的对照观察

目的　比较利培酮与氯氮平治疗对精神分裂症患者生活质量的影响。方法　随机抽取 30例服用利培酮、30例服用氯氮平的精神分裂症患者 ,出院 3个月时用生活质量综合评定问卷 (GQOLI)评估患者的生活质量 ,用阳性症状和阴性症状量表 (PANSS)、不良反应量表 (TESS)评定疗效与副反应。结果　利培酮组GQOLI评分显著高于氯氮平组 (P <0 .0 1) ,TESS评分显著低于氯氮平组 (P <0 .0 1) ,PANSS评分两组差异无显著性 (P >0 .0 5 )。结论　利培酮和氯氮平相比 ,更能提高患者的生活质量 ,在维持治疗方面具有明显的优势     

Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia

BACKGROUND: There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics. We are exploring whether this expanded clinical efficacy can also be seen in patients with treatment-resistant schizophrenia. METHOD: The subjects were 157 treatment-resistant inpatients diagnosed with DSM-IV schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week double-blind trial and rated with a standard measure of clinical antipsychotic efficacy (Positive and Negative Syndrome Scale [PANSS]). Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined. Data were gathered from June 1996 to December 1999. RESULTS: The underlying PANSS factor structure, as indicated by the factor loadings, was essentially identical at baseline and endpoint. At baseline, the excitement factor was followed by the positive, negative, cognitive, and depression/anxiety factors, explaining 49.4% of the total variance. At endpoint, the positive factor was followed by the negative, excitement, cognitive, and depression/anxiety factors, explaining 55.5% of the total variance. The endpoint data indicated statistically significant (p <.05) improvements over time on the positive factor for all 3 atypicals, but not for haloperidol. The negative factor showed significant improvement for clozapine and olanzapine, with significant worsening for haloperidol. Clozapine, olanzapine, and risperidone were superior to haloperidol on the negative factor, while clozapine was also superior to risperidone. The cognitive factor showed significant improvement for all atypicals, as did the depression/anxiety factor. Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone. CONCLUSIONS: Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure. However, antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains (positive, cognitive, and depression/anxiety) of schizophrenia. Clozapine and olanzapine also showed improvement on the negative factor. Only clozapine was associated with improvement on the excitement domain. This finding confirms that atypicals are associated with improvement of an expanded spectrum of symptoms in treatment-resistant patients.     

Phenylpropanolamine appears not to promote weight loss in patients with schizophrenia who have gained weight during clozapine treatment

BACKGROUND: Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight. METHOD: This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly. RESULTS: Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables. CONCLUSION: Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.     

利培酮与氯氮平对精神分裂症患者认知功能影响的对照研究

目的：观察利培酮与氯氮平对精神分裂症患者认知功能的影响。方法：将80例精神分裂症住院患者随机分为两组,并分别予以利培酮与氯氮平治疗12周,于入组前及治疗结束时测查威斯康星卡片分类测验,韦氏记忆测验,阳性和阴性症状量表,并与正常人比较,借以分析两药对认知功能的影响。结果：两组间在威斯康星卡片分类测验,韦氏记忆测验,阳性和阴性症状量表中的认知因子分上并无显著性差异,治疗前后比较利培酮组（40例）在记忆,阳性和阴性症状量表中的认知因子分及威斯康星卡片分类测验中的完成分类数和概念的水平,其百分数有显著差异,而氯氮平组（33例）仅在阳性和阴性症状量表中的认知因子及威斯康星卡片分类测验中的概念水平,其百分数有显著差异,在威斯康星卡片分类测验中完成第一个分类的次数有增加趋势。结论：利培酮对认知功能障碍的治疗作用优于氯氮平。     

利培酮与氯氮平治疗精神分裂症对照研究

目的 评价利培酮治疗精神分裂症的疗效和副作用。方法 将５９例精神分裂症住院病人随机分配到利培酮１组,利培酮２组和氯氮平组（２０例）,治疗８周。用阳性与阴性症状量表（ＰＡＮＳＳ）评定疗效,用副反应量表及锥体外系副反应量表评定副反应。结果 利培酮两个剂量组与氯氮平组之间疗效无显著性差异。在认知因子,阴性因子,ＰＡＮＳＳ总分减分率方面,利培酮组与氯氮平组有显著性差异,利培酮的副反应有锥体外系反应、失眠、     

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.     

迷宫测验与WCST检测利培酮和氯氮平对精神分裂症患者认知功能的影响

目的应用计算机迷宫测验和WCST评估利培酮和氯氮平对精神分裂症患者认知功能的影响。方法63例精神分裂症患者随机分为利培酮组（32例）和氯氮平组（31例），进行双盲给药治疗6周。阳性和阴性症状量表（PANSS）评定临床疗效，计算机迷宫测验和WCST评定认知功能。结果双盲给药的第2周末迷宫测验与WCST成绩呈显著性相关，第6周末仅复杂迷宫测验成绩与WCST中的完成分类数和持续性错误呈非常显著性相关。氯氮平组和利培酮组患者的认知测验成绩均明显改善。阴性症状与认知测验成绩显著相关，而阳性症状的改善与部分认知测验成绩的改善显著相关。结论计算机迷宫测验是一种较好的认知功能评定工具。利培酮和氯氮平均能明显改善精神分裂症患者的认知功能。     

利培酮口服液治疗首发精神分裂症急性期对照观察

目的:探讨利培酮13服液治疗首发精神分裂症急性期的疗效和安全性.方法:96例精神分裂症的急性期患者随机分为两组,分别给予利培酮口服液(研究组,n=49)和氯氮平(对照组,n=47)单药治疗4周.采用阳性和阴性症状量表(PANSS)评定临床疗效,临床总体印象量表(CGI-SI)评定病情严重程度,治疗中出现的症状量表(TE...     

D-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia

BACKGROUND: D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of D-cycloserine when added to risperidone on negative symptoms of schizophrenia. METHOD: Ten patients with schizophrenia who were treated with risperidone completed consecutive two week trials of placebo and four doses of D-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. RESULTS: D-Cycloserine at a dose of 50mg/day was associated with significant reduction in negative symptoms (mean=10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of D-cycloserine. CONCLUSIONS: This preliminary study suggests that combination of D-cycloserine, 50mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of D-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of D-cycloserine with clozapine in previous trials of identical design.     

利培酮与氯氮平治疗首发精神分裂症对认知功能的影响

目的 比较利培酮和氯氮平对首发精神分裂症患者认知功能的影响。方法 将符合入组标准的首发精神分裂症患者77例随机分为利培酮组与氯氮平组,分别进行8周系统治疗,用阳性与阴性症状量表(PANSS)、韦氏成人智力量表(WAIS-RC)、数字划销试验(CT)和临床记忆量表(CMS)进行检查,评估其疗效和对认知功能的影响。结果 脱落4例,73例患者在8周治疗后PANSS总分明显下降(P<0.01),两组之间差异无显著性(P>0.05)。利培酮组的WAIS-RC、CT、CMS总分均明显高于氯氮平组,差异有显著性(P<0.05～0.01)。结论 利培酮对首发精神分裂症患者认知功能的影响明显好于氯氮平。     

利培酮和氯氮平对精神分裂症患者P300影响的随机对照研究

目的探讨精神分裂症患者P300的变异,以及氯氮平和利培酮对P300的影响。方法63例精神分裂症患者随机分为利培酮组（32例）和氯氮平组（31例）,进行双盲给药治疗6周。阳性和阴性症状量表（PANSS）评定临床疗效,同时进行P300检测。结果双盲用药后第6周末,两组患者PANSS总分及各分量表分均明显低于第2周末,差异具有显著性,两组之间差异无显著性。与正常组比较,利培酮组和氯氮平组N1潜伏期、P3潜伏期、P3-N1潜伏期之差明显延长,P3波幅明显降低,差异均具有显著性。经利培酮和氯氮平治疗后两组患者潜伏期和波幅自身前后对比差异均无显著性,两组之间比较差异亦无显著性。氯氮平组患者PANSS阳性症状分与P300的P3潜伏期、P3～N1潜伏期显著负相关,阴性症状分和P3潜伏期明显正相关。利培酮组患者PANSS评分与P300各项指标无明显相关。结论利培酮和氯氮平均能有效治疗精神分裂症患者。精神分裂症患者P300潜伏期和波幅有明显异常,利培酮对P300无明显影响,而氯氮平可能影响P300的潜伏期。     

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.