氯氮平某些副作用对疗效的预测

目的 探索氯氮平治疗第4周末副作用与疗效的关系。方法 给66例精神分裂症患者单服氯氮平,并且评价了0和4周的PANSS,4周的TESS和氯氮平血清浓度。结果 4周TESS的抗5-羟色胺因子分与4周PANSS总分减分率有显著负相关(r=-0.3095,P<0.05),抗5-羟色胺因子分在窗内(1～4分)的显效率17/30比窗外的8/36显著为高x~2=6.862),P<001),相反,氯氟平血清浓度与疗效无显著相关(r=0.1787,P>0.05人氯氮平血清浓度的窗内(200～400μg/L)显效率23/49与窗外2/14无显著差异(x~2=3.592,P>0.05)。结论 4周抗5-羟色胺因子分治疗窗优于4周血药浓度治疗窗。     

利培酮和氯氮平对精神分裂症阴性症状的疗效及不良反应比较

目的比较利培酮与氯氮平对精神分裂症阴性症状的疗效和不良反应。方法应用利培酮和氯氮平治疗精神分裂症各２０例，其阴性症状评定量表评分≥６５分者入组。用阴性症状评定量表（ＳＡＮＳ）评定疗效，用副反应量表（ＴＥＳＳ）评定药物不良反应。结果利培酮和氯氮平对精神分裂症阴性症状的疗效相当，起效时间为２周。两药的副反应不同，利培酮多见锥体外系反应，而氯氮平多见心动过速、嗜睡、流涎、便秘等。结论利培酮对精神分裂症阴性症状有效、疗效与氯氮平相当。     

氯氮平的心脏不良反应

目的：探讨氯氮平治疗精神疾病时的心脏不良反应及危险因素。方法：分析400例服用氯氮平治疗的患者心电图异常改变及其影响因素。结果：服用氯氮平的患者中出现窦性心动过速(发生率79％)、心律失常及传导障碍(4、5％)、ST段压低(3、8％)、T波异常(36．5％)、QTc间期延长(16．3％)等心电图异常。其严重异常发生率为24．3％。服氯氮平出现心脏严重不良反应的危险因素有：男性、合并心血管疾病、治疗前T波异常、服药剂量较大、服药早期。结论：氯氮平的心脏不良反应较常见，约1／4患者可出现严重心电图异常。氯氮平不宜作为首选用药，使用时应定期监测心电图。     

丙戊酸钠对氯氮平血药浓度和疗效的影响

目的:探讨合用丙戊酸钠对氯氮平治疗精神分裂症时的血药浓度和疗效的影响。方法:将80例男性精神分裂症患者随机分为两组,单用组40例患者单服氯氮平,合用组40例患者同时服用氯氮平及丙戊酸钠,分别于治疗前、治疗1周和4周末测定氯氮平的血药浓度,同时评定阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)。结果:合用组治疗1周和4周末有部分患者氯氮平血药浓度升高,部分患者降低,与基线期相比,治疗4周末有显著降低。结论:合用丙戊酸钠后氯氮平血药浓度治疗4周末显著降低;丙戊酸钠可以提高氯氮平对阳性症状的疗效。     

Results and side effects of treatment with clozapine (leponex R)

In the basle Psychiatric University Out-Patient-Clinic 93 randomly chosen patients treated with clozapine were specially examined from 1973–1975. (The percentages are mentioned even when the numbers are small, to give possibilities of comparison.)In schizophrenics the same results were registered when clozapine was given alone or when it was combined with other psychotropic drugs. The young age group of these patients, however, showed more often a deterioration (p < 0.01) in patients treated with clozapine alone. Out of the schizophrenics we had the best results with pure paranoid states, with hebephrenics and catatonics, the least success with paranoid-depressive states (p < 0.01) who showed the same results under clozapine alone and under a combined treatment. The paranoid schizophrenics showed less often a deterioration under treatment with clozapine alone (p < 0.05).The patients with mixed psychoses, manic-depressive psychoses, and involutional depressions showed the same results under clozapine alone and when clozapine was combined with antidepressants and lithium salts.In the treatment of abnormal psychic developments, including neuroses, the same results were obtained when clozapine was given alone or in combination with other drugs. But in this realm it can never be decided definitely what is the psychotherapeutic and what the psychopharmacological effect.Among the side-effects the most serious are the disturbances of hematopoesis. In 9 (25%) of the 36 patients examined with respect to their hematological status, disturbances were registered: 5 patients suffered from leukopenia (except for one all of them had had previous treatments with other major tranquilizers), 6 showed a decrease in polymorphonuclear neutrophils, 2 and eosinophilia, 1 an increase of the number of platelets, 1 an increase of the hemoglobin rate pro erythrocyte (the same patient could have some side-effects). Hematological disturbances were more frequent (p < 0.01) in the young age group (<40 years) if the patients were treated with clozapine alone, and more frequent (p < 0.01) in the group above 40 years if clozapine was combined with other major tranquilizers and other psychotropic drugs.     

米安色林对强迫症的临床疗效及不良反应

目的探讨米安色林对强迫症的临床疗效及不良反应。方法将符合《中国精神疾病分类与诊断标准(第3版)》(CCMD-3)强迫症诊断标准的86例患者,采用随机数字表法分为研究组和对照组各43例,研究组给予米安色林治疗,剂量(132±10.2)mg/d,对照组给予氯丙咪嗪治疗,剂量(182±16.6)mg/d,共12周。在治疗前、4、8、12周末用耶鲁-布朗强迫量表(YALE-BROWN)评定疗效,副反应量表(SERS)评定不良反应。结果治疗第4、8周末研究组YALE-BROWN评分低于对照组,差异有统计学意义(t4=2.254,P0.05;t8=9.476,P0.01);第12周末两组YALE-BROWN评分差异无统计学意义(t12=0.147,P0.05);治疗第4、8、12周末两组SERS评分差异均无统计学意义(t4=0.417,t8=0.497,t12=0.627,P均0.05)。结论米安色林和氯丙咪嗪治疗强迫症的效果和不良反应相当,但米安色林起效快。     

氯氮平血药浓度测定的临床意义

６０例精神分裂症患者单用氯氮平治疗６周，用ＬＣ—６Ａ型液相色谱仪测定氯氮平血浆浓度，结果显示：①氯氮平的血药浓度与剂量达到稳态后有显著相关；②血药浓度与ＢＰＲＳ评分在第一周时有显著相关；③男女性别之间临床症状改善无显著差异；④血药浓度的监测受许多因素影响，其临床意义有待进一步探讨。     

不同剂量氯氮平的血药浓度与临床效应的关系

目的探讨氯氮平血药浓度与临床效应的关系。方法65例精神分裂症患者单用氯氮平治疗。用LC-6A型液相色谱仪测定氯氮平血药浓度,用BPRS和TESS量表评定疗效和副反应。结果氯氮平血药浓度<200ng/ml时疗效欠佳,在200~600ng/ml范围内时疗效最好。氯氮平血药浓度<400ng/ml时与副反应发生率相关性差。但随着血药浓度层次的升高,副反应发生率也升高。结论氯氮平血药浓度以200~500ng/ml作为治疗窗较为合适。     

Comparison of clinical efficacy and side effects for bitemporal and bifrontal electrode placement in electroconvulsive therapy

OBJECTIVES: Bifrontal (BF) placement of electrodes in electroconvulsive therapy (ECT) has become a popular alternative to bitemporal (BT) placement. This study compares the clinical efficacy, side effects, and rehospitalization rates of BT and BF electrode placement in a community hospital setting. METHODS: Charts from 76 patients receiving ECT treatments at Harborview Medical Center from 1994 to 2000 were reviewed to extract data on the characteristics of the course of ECT, clinical response, total headaches, narcotic and nonsteroidal anti-inflammatory drug doses, as well as documentation of confusion, disorientation, memory loss, and treatment emergent need for assistance with activities of daily living. RESULTS: The BT patients experienced more clinical improvement during their stay (a 7-point greater change in Psychiatric Symptom Assessment Scale score, P < 0.05) and were significantly less likely to be rehospitalized within a 1-year time frame (odds ratio = 4.9, P = <0.05), even after controlling for relevant covariates. Although the two patient groups had equal rates of headache and analgesic administration, the BT placement caused significantly more cognitive impairment. CONCLUSIONS: This study suggests that BT electrode placement offers better efficacy but modestly greater cognitive impairment than BF electrode placement.     

氯氮平的早期副作用治疗窗

寻找氯氮平早期副作用治疗窗。方法 给６６例精神分裂症患者单服氯氮平,并且评价了０周ＰＡＮＳＳ、２周ＴＥＳＳ和血清氯氮平浓度、４周ＰＡＮＳＳ和ＴＥＳＳ。结果 ２周ＴＥＳＳ总分和诸因子分与４周ＰＡＮＳＳ总分减分率均无显著相关性,２周抗α１－肾上腺素因子分在窗内（０～５分）的显效率４７％比窗外的２２％显著为高（Ｐ〈０．０５）,２周氯氮平血清浓度在内（２３０～３３０μｇ／Ｌ）的显效率５１％比窗外的１９％显     

Clinical analysis in the main side effects of clozapine: enclosed 600 cases report]

The main side effects of 7921 hospitalized patients taken clozapine from July in 1980 to October in 1988 were investigated. In these cases, there were 600 patients with the main side effects caused by clozapine. They included 312 patients with leukocytosis (52.0%), 114 patients with leukopenia (19.0%), (included 16 patients with agranulocytosis), 53 patients with EEG abnormal (8.9%), 35 patients with fever (5.9%), 32 patients with EKG abnormal (5.3%), 14 patients with rash (2.3%), 12 patients with epileptic seizure (2.0%), 11 patients with posture hypotension (1.8%), 8 patients with paralytic intestinal obstruction (1.3%), 6 patients with SGPT raised (1.0%) and 3 patients with conscious disturbances (0.5%). The causes and treatments of the main side effects mentioned above were discussed.     

氯氮平治疗首发精神分裂症临床效应及影响因素分析

目的　探讨氯氮平治疗首发精神分裂症的效能及影响因素对指导临床用药有很大的实用性。　　方法　 3 0例首发精神分裂症病人均按规定剂量给药 ,选用简明精神症状评定量表 (BPRS)、阴性症状评定量表 (SANS)、临床总体印象量表 (CGI)、总体功能评定量表 (GAF) ,在治疗前及治疗第1、2、4、8、1 2周进行临床评定及血药浓度、催乳素 (PRI)检测 ,治疗前威斯康辛卡片分类测验 (WC ST)。　　结果　氯氮平对首发精神分裂症的阳性、阴性症状均有显著的疗效 ,且起效迅速。此外发现血药浓度大于 40 0 μg/L、基础PRL水平低于 1 1 μg/L、WCST检查表现好的患者 ,选用氯氮平治疗有好的疗效。　　结论　氯氮平可作为较好的一线药物 ,广泛应用于首发精神分裂症的治疗     

Droperidol: efficacy and side effects in psychiatric emergencies.

BACKGROUND: As admission criteria to inpatient units become more focused on patient safety and behavioral instability, primary treatment often requires use of medications that need to be quick, safe, and effective for control of agitation. This article reviews the evidence that droperidol may serve as the optimal medication for this task. DATA SOURCES: A comprehensive MEDLINE search of English-language literature was conducted using the search term droperidol concerning the use of droperidol in psychiatric emergencies. Cross-referencing of those articles was conducted to include pertinent articles in the non-psychiatric and European literature regarding safety and early development of the drug. STUDY FINDINGS: As evidenced in the animal and clinical literature, studies demonstrate the efficacy and rapidity of onset of droperidol and its relative safety compared with the most widely used antiagitation drug, haloperidol. Evidence for this use of droperidol is particularly compelling for situations in which intramuscular administration is necessary. CONCLUSION: Droperidol, while not in widespread use, may prove to be the superior typical neuroleptic for psychiatric emergencies. Increased clinical utilization and study of droperidol for this use is warranted.     

利培酮、氯氮平与氯丙嗪的疗效和不良反应及相关因素的研究

目的　比较利培酮、氯氮平与氯丙嗪的疗效和不良反应 ,探讨有关的实验室检查和药物浓度相互关系。方法　将符合CCMD 2 R诊断标准的精神分裂症患者 ,根据临床情况和入院顺序 ,分别进入利培酮组、氯氮平组与氯丙嗪组 ,观察 8周。以PANSS、CGI、TESS和ESRS量表评定药物的疗效和不良反应。同时测定血清泌乳素和药物浓度。结果　治疗 8周后 :①利培酮组、氯氮平线和氯丙嗪组的PANSS量表总分、阴性分量表、一般精神病理学分量表和CGI量表病情严重程度评分均下降 ,而利培酮组和氯氮平组减分较氯丙嗪组明显 (分别P <0 0 1,P <0 0 5 ) ,TESS及ESRS量表的评分也与氯丙嗪组有显著性差异 (分别为P <0 0 1,P <0 0 5 )。②利培酮组、氯氮平组与氯丙嗪组肝功能、心电图检查组间差异有非常显著意义 (均P <0 0 1)。③氯氮平的剂量与去甲氯氮平、氯氮平浓度呈显著相关 ,9 羟利培酮浓度与PRL、利培酮有效率呈显著性相关 ,氯丙嗪浓度与PRL呈显著性相关 (rs=0 .2 6 1,P =0 .0 15 )。结论　利培酮、氯氮平具有较强抗精神病作用 ,相对氯丙嗪更为有效和全面。利培酮的安全性相对较好。     

Differential effects of clozapine versus other antipsychotics on clinical outcome and dopamine release in the brain

The first atypical antipsychotic, clozapine (Clozaril), dramatically improved the outcome of treatment of patients with schizophrenia in two ways. First, it reduced psychotic symptoms without eliciting significant neurological side effects. Second, it was effective in approximately 30% of individuals who were previously refractory to treatment. Efforts to develop similar drugs have been partially successful in that newer antipsychotics are also less likely to produce neurological side effects. However, it has not yet been established that the newest antipsychotics are more effective than conventional agents in individuals who are refractory to treatment. In the first part of this review, the results of studies that evaluated the new antipsychotics and provided an outcome measure of response rate (regardless of how this index was defined) are summarized. Even with this broad criterion, the evidence suggests that the newer antipsychotics do not share the clinical advantages of clozapine. To explore the possible mechanisms for the clinical advantage of clozapine, evidence of antipsychotic-induced dopamine release in the brain is discussed in the second half of this article. This analysis indicates that acute clozapine administration induces the release of more dopamine in the cortex than in the striatum or limbic system. With conventional antipsychotics, this relationship is reversed. The newest antipsychotics do not show a preference among these sites. Moreover, after long-term treatment, tolerance develops to haloperidol, but not to clozapine, with regard to the amount of dopamine released in the brain. No data are available on the newest antipsychotics. Although more studies need to be done-especially studies of the effects of long-term administration of various conventional and atypical antipsychotics-this distinction might be relevant to the unique clinical advantage of clozapine.     

The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.

OBJECTIVES: This study has been conducted to assess the efficacy and safety of topiramate in refractory epilepsies in infants and young children. METHODS: A prospective clinical trial was performed in three tertiary care hospitals, on 47 children aged 6-60 months with refractory epilepsy. Topiramate was added to at least two baseline anti-epileptic drugs. The efficacy was rated according to seizure type, frequency and duration. RESULTS: Children with refractory epilepsy were classified according to their clinical, neuro-imaging, and neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox-Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%). Children were also classified into cryptogenic and symptomatic epilepsy. Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2 weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%) of the children had a satisfactory response (completely seizure free, or more than a 50% seizure reduction). The remaining 19 children (40%) had an unsatisfactory response (50% or less reduction in seizure frequency, no change or increased seizure frequency). Topiramate appeared to be equally effective in infantile spasms, Lennox-Gastaut syndrome and children with other types of epilepsy, with no significant difference between those with a satisfactory and an unsatisfactory response (p=0.089). There was also no significant difference in response between patients with cryptogenic and symptomatic epilepsy (p=0.360). Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness, were present in 25 (53%) of children. One of the children developed hypothyroidism. CONCLUSION: Although the long term safety and possible adverse effects of topiramate have not been fully established in infants and young children, this study has shown that it is a useful option for children with frequent seizures unresponsive to standard anti-epileptic drugs.     

利福平对氯氮平血药浓度及疗效的影响

目的 :探讨利福平对氯氮平血药浓度及疗效的影响。　方法 :采用自身对照的方法 ,对 30例伴肺结核的精神分裂症患者在原氯氮平治疗的基础上合用利福平 (4 5 0mg/d) ,治疗 6周。以阳性症状与阴性症状量表 (PANSS)评定疗效 ,用高效液相色谱法 (HPLC)测定氯氮平稳态血药浓度。　结果 :合用利福平前与合用后 2、6周末的氯氮平血药浓度分别为 (4 38± 183) μg/L、(10 2± 4 1) μg/L和 (91± 30 ) μg/L ,差异有非常显著性 (F =87 32 ,P <0 0 1)。 30 % (8例 )患者阳性精神症状加重。　结论 :利福平可显著降低氯氮平血药浓度和疗效 ,导致精神分裂症患者阳性症状加重