利培酮与氯氮平对女性精神分裂症患者的心电图影响

目的:研究利培酮与氯氮平对心电图影响的差异.方法:使用ECG-9020机检查60例服用利培酮和30例服用氯氮平的女性精神分裂症患者的心电图变化,并对结果进行分析.结果:服用利培酮后心电图变化异常率为11.7%,服用氯氮平后心电图变化异常率为43.3%,二者有显著差异(P<0.01).结论:提示利培酮对心脏的毒性副作用明显低于氯氮平.     

利培酮与氯氮平治疗精神分裂症疗效比较

目的比较氯氮平与利培酮治疗精神分裂症的效果及不良反应。方法男性精神分裂症患者80例,分为利培酮组40例。年龄（28&#177;6）岁．疗程（5．7&#177;1．6）年,氯氮平组40例,年龄（28&#177;7）岁,疗程（5．1&#177;1．6）年,利培酮组服利培酮剂量,初始1-2mg／d,2周内加至6～8mg／d,氯氮平组服氯氮平剂量．初始50～100mg／d,2周内加至300～400mg／d。8周为1个治疗疗程。采用简明精神病量表（BPRS）副反应量表（TESS）评定疗效和不良反应。结果利培酮组与氯氮平组治疗精神分裂症有效率均为90％（P〉0．05）。2组治疗前、后BPRS评分差异有非常显著意义（P〈0．01）,2组治疗后TESS评分差异有显著意义（P〈0．05）。结论利培酮组与氯氮平组治疗精神分裂症疗效相当．但利培酮组不良反应少。     

利培酮与氯氮平治疗精神分裂症比较

目的 :比较利培酮和氯氮平治疗精神分裂症的疗效和安全性。方法 :利培酮组 30例 (男性 12例 ,女性 18例 ,年龄 34a±s 10a ,BPRS评分 5 4分± 5分 )用利培酮 1～ 8mg/d ,po ,bid ;氯氮平组 30例 (男性 14例 ,女性 16例 ,年龄 33a± 11a ,BPRS评分 5 5分± 5分 )用氯氮平 5 0～ 40 0mg/d ,po ,bid ;均以BPRS ,TESS评定观察 8wk。结果 :利培酮组有效率为 83% ,氯氮平组为 80 % (P >0 .0 5 )。利培酮组对阴性症状起效较早 ,对兴奋躁动控制较差。利培酮组较多见副作用为锥体外系症状 ( 2 7% ) ,与氯氮平组 ( 3% )比较差异有显著意义 (P <0 .0 5 ) ,其他副作用较少而轻。结论 :利培酮与氯氮平疗效相似 ,适宜剂量 (≤ 4mg/d)的利培酮是一种安全有效的抗精神病药。     

氯氮平和利培酮治疗精神分裂症的疗效比较

目的:比较氯氮平和利培酮治疗精神分裂症的疗效和不良反应.方法:符合CCMD 3诊断标准的精神分裂症患者80例,随机分为治疗组和对照组各40例,治疗组给予氯氮平,初始量25 mg&#8226;d 1,po,2周内递增至治疗量200～500 mg&#8226;d 1;对照组给予利培酮,初始量1 mg&#8226;d 1,po,2周内递增至治疗量2～8 mg&#8226;d 1.疗程均为8周.用BPRS评定疗效,用TESS评定不良反应.结果:治疗组和对照组的显效率分别为65.0%,42.5%(P＜0.05).治疗组的主要不良反应为过度镇静、流涎、心动过速及白细胞异常等;对照组的主要不良反应为EPS、失眠、激越及泌乳等.结论:氯氮平治疗精神分裂症起效快且疗效优于利培酮.     

利培酮与氯氮平维持治疗精神分裂症患者的社会功能比较

目的：比较利培酮与氯氮平维持治疗精神分裂症患者的社会功能。方法：对以利培酮与氯氮平治疗痊愈的首发精神分裂症患者随访年，使用社会功能缺陷量表（SDSS）评定其社会功能。结果：利培酮组比氯氮平组社会功能恢复显著（P＜0．01）。结论：利培酮维持治疗精神分裂症具有更好的社会功能。     

利培酮与氯氮平治疗精神分裂症开放性对照研究

目的：考察评价利培酮治疗精神分裂症的疗效。不良反应，耐受性。方法：72例精神分裂症患者随机分组。采用PANSS、CGI和BPRS评定疗效；采用TESS和RSESE量表评定不良反应。结果：36例接受利培酮治疗的患者中有1例因ALT活性升高而脱落（临床评定为无效）。痊愈或显著进步77．8％（28／36），进步11．1％（4／36），无效1．1％（4／36）。利培酮对阳性、阴性症状以及一般精神病态均有良好的效果。该药的锥体外系不良反应较少，主要不良反应有失眠、窦性心动过速、静坐不能、急性肌张力障碍和一过性肝酶活性升高。结论：利培酮治疗精神分裂症的疗效与氯氮平相似，是一种安全、有效的新型抗精神病药。     

利培酮与氯氮平治疗难治性精神分裂症对照研究

目的 比较利培酮与氯氮平治疗难治性精神分裂症的疗效和不良反应. 方法 70例患者随机分为2组, 分别服用利培酮和氯氮平治疗12周, 用阳性与阴性症状量表(PANSS)和不良反应症状量表(TESS)评定疗效和不良反应. 结果 利培酮组总有效率62.9%, 氯氮平组60.0%, 两组差异无显著性(P＞0.05). 结论 利培酮对难治性精神分裂症的疗效与氯氮平相当, 不良反应轻, 易被患者接受.     

利培酮与氯氮平治疗精神分裂症的对照研究

目的:比较利培酮、氯氮平治疗精神分裂症患者的疗效及不良反应。方法:将精神分裂症患者41例随机分成2组,21例予利培酮4～6mg/d治疗,20例予氯氮平250～500mg/d治疗。结果:2组治疗总有效率分别为73.3％,80％,无显著差异(P>0.05),利培酮不良反应少(P<0.05)。结论:两药对精神分裂症阳性、阴性症状均有效。利培酮不良反应少,安全性好。     

Clozapine protects bone mineral density in female patients with schizophrenia

Decreased bone mineral density (BMD) is common in patients with schizophrenia; however, the pathogenesis is unclear. Different classes of antipsychotic agents may affect BMD. This study systemically examined the effects of clozapine vs. other antipsychotics, and several hormonal and metabolic factors that may contribute to BMD in female patients with schizophrenia, who are more vulnerable than males. Forty-eight women with schizophrenia, treated with long-term antipsychotics of the prototype prolactin-sparing (PS) antipsychotic agent clozapine vs. prolactin-raising (PR) antipsychotics were enrolled. They were matched for demographic and clinical characteristics. Various factors, including blood levels of prolactin and sex hormones, psychopathological symptoms, global assessment of functioning, physical activity, and menopausal status, were determined to explore their contribution to low BMD (LBMD), defined as a dual-energy X-ray absorptiometer (DEXA) T score <-1. Overall, women receiving clozapine have better bone density than women receiving PR antipsychotics. Compared to PR antipsychotics, PS clozapine therapy is a protective factor (odds ratio 28.2, 95% confidence interval 2.37-336.10, p=0.008) for LBMD. Predictors for higher bone density in the clozapine group included higher clozapine dose (p<0.001), younger age (p<0.001), and higher thyroid-stimulating hormone level (p<0.001); in the PR group, higher body mass index (p=0.003) and lower alkaline phosphatase level (p=0.007) were associated with LBMD. This study suggests that clozapine treatment is beneficial for BMD compared to PR antipsychotic treatment in women with chronic schizophrenia, and clozapine's bone-density protecting effect is dose-related.     

Clozapine serum concentrations are lower in smoking than in non-smoking schizophrenic patients

Serum concentrations of clozapine and its main metabolite demethylclozapine were measured in 44 schizophrenic inpatients, of whom ten were non-smokers and 34 smokers. When comparing their clozapine dose and body weight-related serum drug levels, we found that clozapine and demethylclozapine concentrations were about 40% lower in the smoking than in the non-smoking group, probably due to an inducing effect of smoking on the cytochrome P450 (CYP) 1A2, which is involved in the metabolism of clozapine. We conclude that dosage adjustment may be necessary in clozapine-treated smokers.     

Clozapine and norclozapine concentrations in serum and plasma samples from schizophrenic patients

At present, the determination of steady-state trough serum/plasma concentrations of clozapine is considered a useful tool for the clinical management of schizophrenic patients treated with this drug. In a previously published study, it was indicated that only plasma should be used to avoid a significant underestimation of clozapine and norclozapine concentrations; however, a formal evaluation of this topic has still not been made, and a consensus on the use of plasma or serum for therapeutic clozapine monitoring may be desirable. Paired samples of serum and plasma (K3EDTA solution contained in Vacutainer tubes) were obtained from 40 schizophrenic patients, and clozapine and norclozapine concentrations were determined by high-performance liquid chromatography. For the parent drug and its metabolite, serum concentrations were higher than in plasma (approximately 7%), although the correction of plasma concentrations in function of hematocrit values reduced this difference to 3%. High correlation coefficients were found between the serum and uncorrected or corrected plasma clozapine concentrations (r = 0.996, P < 0.001), with clinically acceptable differences between the means and standard error of the estimate and consequently with transferability of the results. The clozapine and norclozapine concentrations in five lithium heparin-containing plasma samples (371.9 +/- 226.7 ng/mL and 217.9 +/- 113.1 ng/mL) were analogous to the corresponding hematocrit-corrected EDTA-containing plasma values (374.4 +/- 225.4 ng/mL and 223.5 +/- 115.2 ng/mL), with correlation coefficients of r > or = 0.998 (P < 0.001). Serum or plasma samples may be used for the therapeutic monitoring of clozapine, and no practical advantages have been found with regard to the stability of the drug or imprecision obtained by using either type of biological matrix.     

Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients

The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P < or = 0.005, n = 10) and significantly elevated expression levels of the proapoptotic genes p53 (P < or = 0.020), bax alpha (P < or = 0.001), and bik (P < or = 0.002) in all tested non-CA patients (n = 19) and CA patients (n = 4). In non-CA patients, the expression of these genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P < or = 0.001). Under G-CSF therapy of CA, the number of apoptotic neutrophils and the expression of the proapoptotic genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients.     

Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study

Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and outpatients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228–425) mg/24 h (range 100–700). There was a weak positive correlation between doses and the BPRS total score (r=0.44,P<0.05). The median S-Cloza was 1076 (706–1882) nmol/l (range 196–5581 corresponding to 64–1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r=0.90;P<0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r=0.43;P<0.05). The score values of the UKU Side Effect Scale were weakly (r=0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.     

Clozapine,quetiapine and olanzapine among addicted schizophrenic patients: towards testable hypotheses

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.     

女性首发精神分裂症患者治疗前后性激素水平变化

目的:探讨女性首发精神分裂症患者治疗前后性激素水平变化.方法:对57例女性首发精神分裂症住院患者分别采用利培酮治疗8周后进行开放性对照研究,以阳性和阴性症状量表(PANSS)评估疗效,同时检测治疗前后血清泌乳索(PRL)、雌二醇和睾酮水平.结果:女性精神分裂症患者的基础PRL水平、基础雌二醇及血清睾酮水平与对照组比较差异无显著性(P＜0.05).利培酮治疗8周后患者的PRL水平与治疗前比较有显著升高(P＜0.01).雌二醇和睾酮水平较治疗前显著降低(P＜0.05).治疗8周后患者的PANSS均明显减少,与治疗前相比差异有显著性(P＜0.05).结论:服用利培酮治疗女性首发分裂症能够明显升高血清的PRL,降低雌二醇和睾酮水平,有较强的拮抗中枢多巴胺作用.利培酮对女性精神分裂症患者疗效肯定.     

Clozapine: in prevention of suicide in patients with schizophrenia or schizoaffective disorder

The atypical antipsychotic agent clozapine is associated with a lower propensity for extrapyramidal symptoms than classical antipsychotic agents. The pharmacokinetics of clozapine are affected by wide interpatient variability and a potential for drug interactions. Some studies have shown a relationship between plasma concentrations, duration of treatment and antipsychotic clinical response. Clozapine (mean 274.2 mg/day; n = 490) had a greater preventive effect on suicidality among patients with schizophrenia or schizoaffective disorder at high risk for suicide than olanzapine (mean 16.6 mg/day; n = 490) in a randomised, rater-blinded, multicentre study (p < 0.05; a 22-24% improvement). Other prospective noncomparative trials of the effects of clozapine on suicidal ideation or attempts endorsed these results, while results from retrospective trials are equivocal. Clozapine is commonly associated with sedation, hypersalivation, tachycardia, dizziness, constipation and orthostatic hypotension. Agranulocytosis, diabetes mellitus and weight gain may also occur.     

Serum iron levels in schizophrenic patients with or without akathisia.

The pathophysiology of akathisia still remains controversial. Iron deficiency was proposed to be an important factor in the development of akathisia. In the present study, it was aimed to compare levels of serum iron and linked variables in chronic akathisic (n=30), and non-akathisic patients (n=30) with schizophrenia and healthy controls (n=30) because of the controversy in the association of iron and akathisia. The Barnes Akathisia Scale for akathisia and Simpson-Angus Rating Scale for extrapyramidal side effects were used. Serum iron and linked variables and hematological profile of the patients and control subjects were determined. Serum iron levels were significantly lower both in akathisic and non-akathisic groups compared to the control group (P<0.001). Moreover, akathisic patients had significantly lower iron levels than non-akathisic patients (P<0.05). Total iron binding capacity was significantly higher in patients with akathisia compared to the control group (P<0.01). Although non-akathisic patients had a mild increase in total iron binding capacity, it was not statistically significant compared to the control group (P>0.05). Ferritin levels were determined to be significantly lower in both groups compared to the control group (P<0.01). In addition, there was a significant difference in ferritin levels between the patients with and without akathisia (P<0.05). In conclusion, our results support the hypothesis that an association between akathisia and iron metabolism exists.