帕罗西汀对精神分裂症阴性症状的疗效及对氯氮平血浓度影响的研究

目的 观察帕罗西汀对精神分裂症阴性症状的疗效及对氯氮平血浓度的影响.方法 对40例原服用氯氮平治疗且以阴性症状为主的精神分裂症患者合并帕罗西汀20mg/日治疗12周,分别于合并治疗前及治疗后4周、8周、12周评定阳性症状与阴性症状量表(PANSS)、副反应量表(TESS)及测定氯氮平血浓度.结果 合并帕罗西汀治疗4周、8周、12周末PANSS总分和TESS评分与合并前比较无显著差异(P＞0.05);女性患者合并帕罗西汀治疗4周、8周后氯氮平血浓度明显升高(p＜0.05),但治疗12周后与合并前比较无显著差异,男性患者则氯氮平血浓度无变化.结论 帕罗西汀对精神分裂症阴性症状无明显疗效,使得女性患者氯氮平血浓度有一段时间的升高,对男性患者无影响,合并用药后不良反应也不明显.     

氯氮平合并帕罗西汀治疗精神分裂症阴性症状临床研究

目的　观察氯氮平合并帕罗西汀治疗精神分裂症阴性症状的疗效和副作用。方法　将 66例女性慢性精神分裂症患者平均分为研究组 (氯氮平加帕罗西汀 )和对照组 (氯氮平加安慰剂 )。在治疗前、治疗后 4、8、12周末分别以阳性症状和阴性症状量表(PANSS)和副反应量表 (TESS)评定疗效和副作用。同时测定氯氮平与去甲氯氮平的血浓度。结果　治疗 8周后研究组PANSS总分、阴性因子分比治疗前明显降低 ,且阴性因子分值显著低于对照组 ,氯氮平及去甲氯氮平血浓度明显升高。治疗后 4、8、12周末TESS评分 ,研究组均低于对照组 ,且治疗后低于治疗前 ,均有显著性差异。结论　氯氮平合并帕罗西汀能明显改善精神分裂症患者的阴性症状 ,且副作用减少。     

氯氮平合并碳酸锂治疗男性难治性精神分裂症的对照研究

目的比较氯氮平和氯氮平合并碳酸锂治疗男性难治性精神分裂症的疗效和不良反应．方法将72例男性难治性精神分裂症患者随机分为两组，分别应用氯氮平和氯氮平合并碳酸锂治疗8周．采用阳性和阴性症状量表（PANSS）和不良反应量表（TESS）评定疗效和不良反应。结果治疗结束时，两组PANSS因子分值较治疗前均有明显降低，且有统计学意义。氯氮平合并碳酸锂组阳性症状因子减分早于氯氮平组，且两组间有显著性差异（P〈0．05）。氯氮平合并碳酸锂组总有效率为75％，明显高于氯氮平组的47．1％（P〈0．05）。结论氯氮平合并碳酸锂治疗男性难治性精神分裂症疗效优于氯氮平。     

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。     

奥氮平与氯氮平治疗精神分裂症一年随访对照研究

目的前瞻性随访对照研究奥氮平（悉敏）与氯氮平治疗精神分裂的疗效与不良反应。方法研究对象为我院2个治疗病房的患者,奥氮平组84例,氯氮平组88例,评定两组患者入组前阳性阴性症状量表（PANSS）和治疗2,4,12,52周的PANSS量表及副反应量表（TESS）的测定,同时随访血糖、脑电图。结果（1）治疗2周两组PANSS量表均显著下降,以阳性症状改善明显,说明奥氮平与氯氮平对精神分裂症患者急性期的治疗均有效;（2）经随访研究1年后两组PANSS量表阳性、阴性、精神病性症状分均显著下降,奥氮平与氯氮平比较阴性症状改善更显著（P〈0.05）;（3）奥氮平血象、心电图、脑电图异常及嗜睡、便秘发生率均较氯氮平低,差异具有显著性;（4）奥氮平所致的体重增加在12周时与氯氮平比较无差异,随访1年差异显著。结论奥氮平治疗精神分裂症急性期症状疗效与氯氮平相当,随访研究1年对阴性症状的改善优于氯氮平且安全性高。     

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。     

帕罗西汀合并氯氮平治疗精神分裂症的阴性症状

目的探讨氯氮平合并帕罗西汀治疗精神分裂症的阴性症状的疗效。方法以阴性症状为主、单用氯氮平的住院精神分裂症病人58例，随机分成研究组和对照组，分别加用帕罗西汀和安慰剂治疗，疗程12周，使用阳性症状与阴性症状量表（PANSS）和副反应量表（TESS）评定，在治疗前和治疗4、8、12周末备评定一次。结果研究发现两组疗效相比较，两组疗效相仿（P〉0．05）。两组治疗前后PANSS总分、阴性因子分评分比较，显效时间均在用药8周后。12周末研究组PANSS总分、阴性因子分明显低于治疗前，而且两组间比较发现研究组阴性因子分比对照组明显降低，提示存在显著差异（P〈0．01）。结论帕罗西汀合并氯氮平能够显著改善精神分裂症的阴性症状。且少有副反应。     

利培酮合并舍曲林治疗慢性精神分裂症的对照研究

目的评价利培酮合并舍曲林治疗慢性精神分裂症阴性症状和副作用。方法将64例慢性精神分裂症患者随机分为单用组（利培酮组）与合用组（利培酮十舍曲林组）,采用阳性症状和阴性症状量表（PANSS）、阴性症状量表（SANS）和副反应量表（TESS）分别于治疗前、治疗后4、8、12周进行疗效及副反应评定。结果治疗8周后合用组PANSS总分、阴性因子分、SANS总分及分量表分均比治疗前明显下降,且阴性因子分显著低于单用组。治疗后4、8、12周TESS评分,合用组低于单用组。结论利培酮合并舍曲林能明显改善慢性分裂症,且副作用较少。     

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。     

无抽搐电休克合并奥氮平治疗难治性精神分裂症对照研究

目的探讨无抽搐电休克治疗（MECT）合并奥氮平（悉敏）对难治性精神分裂症的疗效及安全性。方法将63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MECT合并奥氮平和单用奥氮平治疗。观察期为12周。分别采用阳性和阴性症状量表（PANSS）、韦氏记忆量表（WMS）及副反应量表（TESS）评定疗效及安全性。结果（1）治疗2周末,MECT合并奥氮平组PANSS量表总分及阳性症状分较前明显下降（P〈0．05）,治疗4周末,奥氮平合并MECT组PANSS量表总分及阳性症状分较单用奥氮平组明显下降（P〈0．01）,治疗12周后,两组PANSS量表总分、阳性症状分、阴性症状分均较治疗前有显著性下降（P〈0．01）;（2）总有效率两组分为67．74％和62．50％,组间比较无差异（P〉0．05）;（3）奥氮平合并MECT组在MECT治疗期间WMS分明显下降（P〈0．01）,但在MECT结束治疗后4～8周恢复,与单用奥氮平组相比无显著性差异（P〉0．05）;（4）两组均未见严重的不良反应。结论MECT合并奥氮平治疗难治性精神分裂症疗效肯定,安全性好,快速控制阳性症状的疗效优于单用奥氯平。     

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。     

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.     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.     

Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication. METHOD: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.     

Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.     

Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials

OBJECTIVE: The authors conducted a review and meta-analysis of studies that compared the efficacy and tolerability of typical and second-generation antipsychotics for patients with treatment-resistant schizophrenia. METHOD: A systematic search revealed 12 controlled studies (involving 1,916 independent patients), which were included in the review. For the seven studies that compared clozapine to a typical antipsychotic, a meta-analysis was performed to examine clozapine's effects on overall psychopathology, response rate, extrapyramidal symptoms, and tardive dyskinesia. RESULTS: The meta-analysis confirmed that treatment-resistant schizophrenic patients have more favorable outcomes when treated with clozapine rather than a typical antipsychotic, as reflected by Brief Psychiatric Rating Scale total score, categorical response rate, Scale for the Assessment of Negative Symptoms score, Simpson-Angus Rating Scale score, and compliance rate. Clozapine also conferred benefits on the sickest treatment-resistant schizophrenic patients. Patients treated with olanzapine also had more favorable outcomes with regard to categorical response and compliance rates. CONCLUSIONS: In the aggregate, the results of a meta-analysis indicated that clozapine exhibits superiority over typical antipsychotics in terms of both efficacy (as measured by improvement in overall psychopathology) and safety (in terms of reduced extrapyramidal side effects). However, the magnitude of the clozapine treatment effect was not consistently robust. Efficacy data for other second-generation antipsychotics in the treatment of patients with refractory schizophrenia were inconclusive. There is, therefore, a growing need to consider new and different treatment strategies, whether they be adjunctive or monotherapeutic, for schizophrenia that continues to be resistant or only partially responsive to treatment.     

Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia

BACKGROUND: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. METHODS: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.     

奥氮平与利培酮治疗难治性精神分裂症的对照研究

目的 比较奥氮平与利培酮对难治性精神分裂症的疗效及安全性.方法 68例难治性精神分裂症患者按照排列表法随机分为奥氮平组[34例,(24.1±5.4)mg/d]和利培酮组[34例,(7.9±1.8)mg/d],疗程均为12周.采用阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)及治疗中需处理的不良反应症状量表(TESS),在治疗前及治疗第1,2,4,8,12周末分别评定疗效和不良反应.结果 (1)奥氮平组PANSS总分、阳性症状分、阴性症状分及一般病理分均从治疗第2周末起较治疗前下降(P<0.05～0.01);利培酮组PANSS总分、阳性症状分、一般病理分从治疗第2周末起,阴性症状分从第4周末起,较治疗前下降(P<0.05～0.01);奥氮平组从治疗第2周末起各时点PANSS总分、阴性症状分均低于利培酮组(P<0.05～0.01).(2)治疗第2周末起,2组临床总体印象量表-严重程度和改善程度(CGI-SI)总分均较治疗前下降(P<0.05～0.01);2组间各时点CGI-SI分的差异无统计学意义(P>0.05).(3)治疗第12周末,奥氮平组、利培酮组临床总有效率分别为65%、41%,差异有统计学意义(P<0.05).(4)奥氮平组、利培酮组不良反应发生率分别为53%(18/34)和59%(20/34),差异无统计学意义(P>0.05);奥氮平组体质量增加发生率高于利培酮组(P<0.05);利培酮组静坐不能、异常泌乳和(或)闭经、肌张力增高的发生率高于奥氮平组(P<0.05).结论 奥氮平对难治性精神分裂症有良好疗效,不良反应轻微.     

Adverse Effects and Laboratory Parameters of High-Dose Olanzapine vs. Clozapine in Treatment-Resistant Schizophrenia

Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine.     

Treatment-resistant schizophrenic patients respond to clozapine after olanzapine non-response.

BACKGROUND: Treatment-resistance in schizophrenia remains a public health problem. Clozapine has been shown to be effective in about one third of this population, but carries with it medical risks and weekly blood draws. As olanzapine is a drug with a very similar biochemical profile to clozapine, it is important to evaluate whether non-response to olanzapine predicts clozapine non-response. METHODS: Forty-four treatment-resistant patients received eight weeks of olanzapine, either in a double-blind trial or subsequent open treatment at a mean daily dose of 25 mg/day. Two of 44 patients (5%) responded to olanzapine treatment. Patients who did not respond could then receive clozapine. Twenty-seven subsequently received an 8-week open trial of clozapine. RESULTS: Patients who did and did not receive clozapine did not differ demographically or in psychopathology. Eleven of 27 (41%) met a priori response criteria during clozapine treatment (mean dose 693 mg/day) after failing to respond to olanzapine. CONCLUSIONS: This study demonstrates that failure to respond to olanzapine treatment does not predict failure to clozapine. Treatment-resistant patients who fail on olanzapine may benefit from a subsequent trial of clozapine.