15例难治性精神分裂症患者由氯氮平换用喹硫平治疗的临床报告

虽然氯氮平是治疗精神分裂症的二线药物,并能够将其他抗精神病药物治疗无效的精神分裂症的疗效提高30％左右,但仍然有部分患者对氯氮平治疗无效,或不能耐受氯氮平的不良反应,此时就需要将氯氮平换为其他精神病药物。但由于撤药综合征的问题,氯氮平换用其他抗精神病药物被大部分精神科医生视为临床难题。本文就此总结了15例服用氯氮平的精神分裂症患者换用喹硫平的临床特点。     

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。     

Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia

BACKGROUND: Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine. OBJECTIVE: The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials. CONCLUSION: Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.     

Schizophrenic syndromes and clozapine response in treatment-resistant schizophrenia

Relationships between symptom profile and clozapine response were studied. Symptom scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms were subjected to principal component analysis (PCA) in a group of 66 treatment-resistant schizophrenic patients, 49 of whom were treated with clozapine. Factor scores were compared among responders, non-responders and partial responders. The PCA yielded a four-factor solution, with positive symptoms, negative symptoms, cognitive disorganization and behavioral disorganization components. Cognitive and behavioral disorganization syndrome scores showed significant differences across groups. Cognitive disorganization was higher in non-responders, while behavioral disorganization was higher in partial responders. The results support the possibility of using clinical profiles to predict therapeutic response to clozapine.     

Differences of satisfaction with medication between patients with schizophrenia treated with typical antipsychotics and atypical antipsychotics

Many studies have demonstrated that atypical antipsychotics are superior to typical antipsychotics in that they have fewer side-effects and produce better improvement of cognitive deficits and quality of life in patients with schizophrenia. However, most of these studies dealt with objective indices assessed by researchers rather than subjective indices that are indeed important to patients themselves. In 126 patients with schizophrenia, annoyance of side-effects and psychotic symptoms, satisfaction with medication, wish to change medication, and knowledge of atypical antipsychotics were assessed using questionnaires. Patients treated with typical antipsychotics complained less of annoyance of poor attention and concentration than those treated with atypical antipsychotics, which can be explained by increased awareness of these symptoms by the patients due to the improvement of cognitive function. There were no significant differences between the two groups in other variables. The present results that satisfaction and annoyance were similar between patients treated with typical antipsychotics and those with atypical antipsychotics, may partly explain why patients hesitated and rejected changing or shifting from typical to atypical antipsychotics. But because 98 of 126 patients did not know about atypical antipsychotics, it is important to educate the patients on the merits of atypical antipsychotics.     

Combined electroconvulsive therapy and clozapine in treatment-resistant schizophrenia.

1. To assess the efficacy and safety of combining electroconvulsive therapy (ECT) and clozapine in patients with treatment-resistant schizophrenia, the authors reviewed use of this combination in four treatment-resistant schizophrenic inpatients and one inpatient with schizophrenia who was intolerant of clozapine doses needed to control her psychosis. 2. The combination of clozapine and bilateral ECT was modestly effective in two treatment-resistant patients and markedly effective in three patients. There was significant overall improvement in patients' Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) scores (p < 0.005 and p < 0.0004, respectively), however in patients where marked symptomatic improvement was noted, effects were not sustained. 3. One of the patients that showed dramatic yet transient improvement followed by relapses received maintenance ECT but relapsed despite this. 4. The authors saw no adverse effects in connection with the combination of ECT and clozapine. 5. Supplementing clozapine with a course of bilateral ECT appears to be safe and is effective in some patients with refractory schizophrenia, however its beneficial effects may be short-lived. The long-term impact of ECT on the course of schizophrenia in patients incompletely responsive to clozapine is not fully elucidated.     

Effect of typical antipsychotic medications and clozapine on smooth pursuit performance in patients with schizophrenia.

The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye movements was tested in 13 patients with schizophrenia or schizoaffective disorder with a repeated measures design. Nineteen normal control subjects were also studied. Compared with controls, patients in the unmedicated state had low smooth pursuit gain, had a higher rate of corrective catch-up saccades, and tended to spend less time engaged in the tracking task. The patients did not significantly differ from controls on catch-up saccade amplitude, square wave jerk rate, or anticipatory saccade rate. Medication with clozapine, but not typical neuroleptics, was associated with an increase in median catch-up saccade amplitude. Number of days on clozapine and clozapine dose both correlated significantly with a worsening of oculomotor performance. No effect of medication with typical neuroleptics was found, although there was some evidence suggesting that such an affect may occur after more prolonged treatment.     

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。     

Association between subjective well-being and depressive symptoms in treatment-resistant schizophrenia before and after treatment with clozapine

Background

We examined the relationship between subjective well-being and depressive symptoms in patients with treatment-resistant schizophrenia before and after treatment with clozapine to contribute to the growing body of research regarding the determinants of patients' perspective of their own well-being in schizophrenia.

Methods

Forty patients with treatment-resistant schizophrenia were comprehensively evaluated for subjective well-being, schizophrenic symptoms, and depressive symptoms before and 8 weeks after the initiation of treatment with clozapine. Correlation analysis and Fisher's z-transformation statistics were performed.

Results

There were significant improvements in all Positive and Negative Syndrome Scale (PANSS) factor scores and Beck Depression Inventory (BDI) score over the treatment period (P < .05). Before clozapine administration, the subjective well-being score had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05). After clozapine treatment, the subjective well-being score still had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05) and no new associations emerged with treatment. Fisher's z-transformation statistics revealed that the correlations between the subjective well-being score and the depression score were not significantly different before and after clozapine treatment.

Conclusions

These results indicate that depressive symptoms are significantly associated with low subjective well-being in patients with treatment-resistant schizophrenia. The association was equally significant before and after treatment with clozapine, suggesting that the relationship does not change with clozapine treatment, even when depressive symptoms improve significantly, and that there may be a common pathophysiological basis for depressive symptoms and the subjective appraisal of well-being in schizophrenia.     

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression. In the present study, we assessed serum BDNF immunoreactivity in 44 schizophrenic patients (20 on clozapine and 24 on typical antipsychotics) and in 25 healthy volunteers. Serum BDNF levels were measured using an enzyme immunoassay. Healthy controls showed significantly higher levels of BDNF compared to the whole group of schizophrenic patients (p<0.001) as well as to the subgroups on typical antipsychotics and clozapine (p<0.001). Serum BDNF values for controls were 168.8+/-26.3pg/ml, for the clozapine group were 125.4+/-44.5pg/ml and for the group on typicals were 101.3+/-51.6pg/ml. BDNF values from patients on clozapine were non-significantly higher than values from patients on typical antipsychotics (p=0.09). Serum BDNF was strongly and positively correlated with clozapine dose (r=0.643; p=0.002) but not with other demographic characteristics. These results reinforce previous findings of reduced serum BDNF levels in schizophrenic patients and suggest a differential effect of clozapine compared to typical antipsychotics on such levels.     

Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia

Clozapine alleviates the symptoms of a significant proportion of treatment-resistant schizophrenic patients. Previous studies suggest that the response to clozapine may be associated with prefrontal and temporal anatomy as well as with prefrontal, basal ganglia and thalamic metabolism. A sample of 25 treatment-resistant (TR) schizophrenic patients underwent magnetic resonance imaging (MRI) and 18F-deoxyglucose positron emission tomography (PET) before and after treatment with clozapine. We investigated the association between changes in positive, disorganized, and negative schizophrenic syndromes with clozapine treatment and a set of cerebral variables that included total intracranial volume (ICV); hippocampal, dorsolateral prefrontal (DLPF) and temporal gray-matter volume and metabolism; and metabolic activity of the thalamus, pallidum/putamen, and caudate head. Improvement in positive symptoms with clozapine was directly related to temporal gray-matter volume, whereas improvement of disorganization symptoms was inversely related to ICV and hippocampal volume. Patients with high baseline DLPF cortical volume and metabolic activity were more likely to experience improvement in their negative symptoms. We conclude that clinical improvement with clozapine may be related with the anatomy and metabolic activity of specific brain areas, with the structural integrity of the DLPF and temporal regions showing the maximum predictive capacity.     

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.     

难治性精神分裂症氯氮平联合用药的德尔菲法调查

目的:调查难治性精神分裂症(TRS)氯氮平联合用药的现状.方法:通过德尔菲法对南方4省8家精神专科医院进行3轮专家咨询,得出氯氮平单药治疗TRS疗效欠佳者(超难治性精神分裂症,STRs)的氯氮平联合用药治疗方案.结果:首轮调查在TRS定义等7个方面共22项意见中,有14项的认同率超过2/3,达成专家共识.获得了10种不...     

Evaluation of subjective treatment satisfaction with antipsychotics in schizophrenia patients

Adherence to antipsychotic treatment is particularly important in the long-term management of schizophrenia and other related psychotic disorders since poor adherence to medication is associated with poor health outcomes. Although the patients' subjective satisfaction with the medication is crucial for adherence to medication, few studies have examined the relationship between subjective satisfaction with antipsychotics and adherence. In this study, we investigated subjective satisfaction with antipsychotics in patients with schizophrenia by using the Treatment Satisfaction Questionnaire for Medication (TSQM), a self-reporting instrument to assess the major dimensions of patients' satisfaction with their medication. The subjects included 121 clinically stabilized outpatients who met the following criteria: 1) patients between 20 and 65 years of age, diagnosed with schizophrenia or other psychotic disorders as defined by DSM-IV, 2) patients undergoing oral antipsychotic monotherapy or taking only an antiparkinsonian agent as an adjuvant remedy, and 3) patients who had received a stable dose of an antipsychotic for more than four weeks. Patients were asked to answer the TSQM questions, and their clinical symptoms were also evaluated by the Brief Psychiatric Rating Scale (BPRS). Satisfaction with regard to side-effects (p=0.015) and global satisfaction (p=0.035) were significantly higher in patients taking second-generation antipsychotics (SGAs, n=111) than those taking first-generation antipsychotics (FGAs, n=10), whereas no significant difference was found between the two groups in clinical symptoms according to BPRS (p=0.637) or the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS, p=0.209). In addition, correlations were not significant between the subjective satisfactions and clinician-rated objective measures of the symptoms. These findings suggest that SGAs have more favorable subjective satisfaction profiles than FGAs in the treatment of schizophrenia. Since it is often difficult to detect the difference by a traditional objective assessment of the patients, it is desirable that physicians pay attention to the patients' subjective satisfaction in conjunction with their own objective clinical assessment.