利培酮致粒细胞减少1例

患者男，28岁。诊断精神分裂症。因出现强迫动作，加用氯米帕明治疗，症状无明显改善。改用利培酮与牛黄宁宫片（12片／d），利培酮起始剂量4mg／d，1个月改为6mg／d，10个月后改为5mg／d，曾查血常规正常。1年以后查血常规白细胞（WBC）1．7×10^9T／L，淋巴细胞（L）0．35，中性粒细胞（G）0．47，即入院治疗。入院后行骨髓穿刺，外周血片共数白细胞100个，骨髓片共数有核细胞200个，见有核细胞增生活跃，粒细胞系统增生明显减低，     

喹硫平所致血小板减少症1例

患者男性,68岁,未婚。因兴奋话多、猜疑、加重2天,于2008年1月3日第二次住院,诊断精神分裂症。入院后给予利培酮（维思通）治疗,逐渐增加至3mg／日,病情有进步,因锥体外系反应明显而不能耐受,于3月18日～20日逐渐停用利培酮,3月20日起给予喹硫平25mg／晚。3月12日查血常规示血小板计数146×10^9／L,3月21日复查血小板计数87×10^9／L,     

入院当日白细胞状况对急性缺血性脑卒中出院当日MRS评分的影响

目的探讨入院当日白细胞计数和中性粒细胞比率对急性缺血性脑卒中(AIS)患者出院当日MRS评分的影响,为科学评估住院期间病情转归提供依据。方法采用回顾性队列研究的方法,录入2011.6.1-2014.6.1阜新市中心医院3151例AIS患者,收集人口统计学、生活方式及入院当日白细胞计数,中性粒细胞比率等血常规信息。出院当日按照生活质量评分量表(MRS)评分将研究对象分为2组:MRS≥3分为神经功能缺损组,MRS3分为对照组。按照白细胞计数(≤10.0×10~9·L~(-1),10.1～11.0×10~9·L~(-1),11.1～12.0×10~9·L~(-1),≥12.1×10~9·L~(-1))水平将研究对象分为4组,按照中性粒细胞比率(≤70.00%,70.01-80.00%,≥80.01%)将研究对象分为3组,采用Logistic回归分析白细胞计数及中性粒细胞比率对AIS出院当日MRS评分的影响。结果 MRS≥3分组的白细胞计数、中性粒细胞比率均高于MRS3分组,差异有统计学意义(P0.05);经多因素校正后,白细胞计数与第1组相比,第2、3和4组均增加了AIS发生MRS评分增高神经功能缺损的风险,OR值及95%CI分别为1.700(1.103～2.620),2.756(1.714～4.433),3.355(2.453～4.589);中性粒细胞比率与第1组相比,第2和3组均增加了AIS患者MRS评分增高神经功能缺损的风险;并且随着白细胞计数和中性粒细胞比率的增加,残疾和死亡复合结局的风险也随着增加(P趋势性检验0.0001)。结论 AIS患者入院当日白细胞计数增加及中性粒细胞比率升高加大了出院当日MRS评分增高的风险,并存在计量反应关系。     

氯氮平致全身皮肤粘膜广泛性出血1例报告

氯氮平引起的粒细胞缺乏及其他严重副反应国内外报道很多。但导致全身皮肤粘膜广泛性出血的病例报道甚少。现报告1例如下: 患者男性,18岁,学生。因自语自笑、行为怪异、打骂家人2年于1993年4月18日上午首次收住院。无治病史。入院时查心脑电图均正常,白细胞6.8×10~9/L     

吸烟对男性精神分裂症患者临床症状的影响及可能机制

目的探讨吸烟对男性精神分裂症患者临床症状的影响及氧化应激在精神分裂症高吸烟率中的作用。方法研究共入组男性精神分裂症患者130例,根据目前的吸烟状况分吸烟组（74例）和非吸烟组（56侧）,运用阳性和阴性症状量表（PANSS）评定精神病理症状;采用分光光度法检测其血浆超氧化物岐化酶（SOD）、过氧化氢酶（CAT）活性以及丙二醛（MDA）浓度。结果（1）吸烟组PANSS阳性症状（14．5±6．3）分显著低于非吸烟组（17．5±4．9）分（P〈0．05）;吸烟组患者吸烟数量与PANSS阴性症状分显著负相关（r=-0．23,P=0．02）。（2）血浆CAT活性吸烟组（2．9±0．3）×10^3U／L显著高于非吸烟组（1．6±0．2）×10^3U／L,吸烟患者血浆SOD活性与吸烟数量显著相关（r=0．24,P=0．04）;血浆MDA浓度吸烟组（9．2±0．7）mmol／L显著低于非吸烟7组（14．4±1．7）mmol／L。结论男性精神分裂症患者的吸烟可能通过缓解氧化应激来改善部分精神病理症状。     

维思通致粒细胞减少一例报告

维思通是近年投入临床的一种新型抗精神病药物，因其能同时改善精神分裂症的阴性、阳性症状，且锥外系反应发生较少而轻微，很快受到病人及医生的欢迎。对于维思通引起的粒细胞减少，国内外报道较少，笔者曾在临床上遇到1例，现报道如下。郝××，男，33岁，住院号：25519，因患精神分裂症人院治疗，人院查血白细胞总数为7．1×109／L。入院后单一使用维思通治疗，当维思通增至5mg／日时，患者出现血白细胞总数下降（3．8×109／L），次日复查血白细胞总数仍偏低，逐将维思通减至3mg／日，一周后患者血白细胞总数升至4．7×109／L。后由于…     

精神药物所致粒细胞缺乏症在抢救过程中对并发症的处理

精神药物所致粒细胞缺乏症在抢救过程中对并发症的处理山东省青岛市精神病医院（２６６０３３）岳德华上海市精神卫生中心王祖承在抗精神病药物应用过程中，粒细胞缺乏症（白细胞计数少于２．０×１０９／Ｌ，中性粒细胞少于１．０×１０９／Ｌ）已日益受到精神科临床的重...     

文拉法辛结合认知治疗神经性厌食症1例

1病例 患者女性，24岁，汉族。因胸闷、乏力、气短入住心内科。身高170cm，体质量40kg，体质量指数（BMI）13．8，近4个月体质量减轻15kg，进食后频繁呕吐影响工作，继发闭经8个月。入院检查：心电图示心动过缓，心率39次／分，心肌缺血；血常规：红细胞3．0×10^12／L，白细胞3．0×10^9／L，血红蛋白60g／L，总三碘甲状腺原氨酸、总甲状腺素、     

奎硫平致白细胞减少及血红蛋白下降1例

病例 患者，男，29岁。因复起疑人跟踪，凭空闻声，行为异常5d入院，诊断：精神分裂症。入院时查血常规：白细胞5．9×10^9／L，血红蛋白117g／L。     

阿立哌唑致白细胞降低1例

1病例 患者女,31岁,白族,高中文化程度。近2个月来因无明显诱因傻笑,工作能力下降,怀疑有人在杯子里下毒,有人用电脑控制自己而住院,诊断：精神分裂症。入院时查血常规：白细胞5.8×10^9/L,中性粒细胞66%,淋巴细胞28%。给予阿立哌唑10mg/d治疗,精神症状逐渐缓解。     

Are clozapine blood dyscrasias associated with concomitant medications?

Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are reported in this article, as well as the possible duration of medication use prior to induction of an adverse drug reaction.     

Attitudes of schizophrenia outpatients toward psychiatric medications: relationship to clinical variables and insight

BACKGROUND: Attitude toward medications is important for medication adherence. A patient's drug attitude probably reflects a weighing of benefits against experienced or anticipated side effects or risks associated with the medication. We predicted (1) that drug attitudes would be more positive among schizophrenia patients taking second-generation compared to first-generation antipsychotics because of their greater tolerability and efficacy; and (2) that greater insight into illness, fewer extrapyramidal symptoms, and better social functioning would be associated with better attitudes toward psychiatric medication. METHOD: In a cross-sectional study of 81 DSM-IV-diagnosed schizophrenia outpatients, we used multivariate analysis to determine clinical and demographic predictors of drug attitude. Drug attitude was assessed with the 10-item Drug Attitude Inventory (DAI). The relationship between the DAI and psychopathology, insight, extrapyramidal symptoms, level of functioning, and type of antipsychotic (first-generation versus second-generation versus clozapine) was examined. RESULTS: Less awareness of current symptoms, presence of deficit symptoms, and employment predicted a negative attitude toward psychiatric medications. Extrapyramidal symptoms did not predict drug attitude. Drug attitudes were no different between patients taking first- or second-generation antipsychotics or clozapine. CONCLUSION: Patients may not favor second-generation over first-generation antipsychotics, and extrapyramidal symptoms may not be a primary factor determining attitudes. While attitudes may be more positive in patients who recognize therapeutic drug effects, patients who work may view medications particularly negatively, possibly due to a sense of stigma. Because drug attitudes may reflect compliance and are difficult to predict, clinicians should inquire directly.     

奥氮平与氯氮平治疗巴金森病精神症状的对照

目的:对比奥氮平和氯氮平治疗巴金森病中精神症状的疗效与不良反应。方法:对27例奥氮平和25例氯氮平治疗的存在精神症状的巴金森病患者,在治疗的0、2、4、6周分别评定简明精神病评定量表(BPRS)、治疗中出现的症状量表(TESS)、锥体外系副反应量表(RSESE),对比两组间疗效与不良反应的差别。结果:2周时两组BPRS评分均较治疗前有显著性降低(P均<0.05)。两组间BPRS、RSESE评分在不同时间差异均无显著性(P均>0.05)。2、4、6周时奥氮平组的TESS评分明显低于氯氮平组,两组间差异有显著性(P<0.05)。结论:奥氮平和氯氮平对治疗巴金森病中精神症状的疗效相似,均未明显增加巴金森病的锥体外系反应。奥氮平的不良反应低于氯氮平。     

Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy.

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurological comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic features. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be monitored carefully.     

Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia

In 200 inpatients on regular neuroleptics, point prevalence of extrapyramidal syndromes, including Parkinson syndrome, akathisia and tardive dyskinesia (TD), was studied and found to be 20, 11 and 22%, respectively. A total of 46 patients have currently, and for a longer time, (average about 3years, median over 1year) been treated with clozapine, and 127 with typical neuroleptics (NLs). Comparing both groups, higher TD scores were found in the clozapine sample. Investigating the influence of a set of seven clinical variables on the TD score with the help of multiple regression analysis, the influence of the treatment modality disappeared, whereas the age proved to be the only significant variable. Studying the role of past clozapine therapy in patients currently on typical NLs and comparing 10 matched pairs of chronic patients with and without TD in whom a complete life-time cumulative dose of NLs was identified, a relationship between TD and length of current typical NL therapy and life-time typical NL dosage could be demonstrated. On the whole, long-term relatively extensive use of clozapine has not markedly reduced the prevalence of extrapyramidal syndromes in our psychiatric inpatient population. In particular, we failed to demonstrate a beneficial effect of clozapine on prevalence of TD. There are certainly patients who suffer from TD in spite of a long-term intensive clozapine treatment.     

Cost-effectiveness of clozapine compared with conventional antipsychotic medication for patients in state hospitals

BACKGROUND: An open-label, randomized controlled trial compared clozapine with physicians'-choice medications among long-term state hospital inpatients in Connecticut. The goal was to examine clozapine's cost-effectiveness in routine practice for people experiencing lengthy hospitalizations. METHODS: Long-stay patients with schizophrenia in a state hospital were randomly assigned to begin open-label clozapine (n = 138) or to continue receiving conventional antipsychotic medications (n = 89). We interviewed study participants every 4 months for 2 years to assess psychiatric symptoms and functional status, and we collected continuous measures of prescribed medications, service utilization, and other costs. We used both parametric and nonparametric techniques to examine changes in cost and parametric analyses to examine changes in effectiveness. We used bootstrap techniques to estimate incremental cost-effectiveness ratios and create cost-effectiveness acceptability curves. RESULTS: Both groups incurred similar costs during the 2-year study period, with a trend for clozapine to be less costly than usual care in the second study year. Clozapine was more effective than usual care on many but not all measures. With the use of effectiveness measures that favored clozapine (extrapyramidal side effects, disruptiveness), bootstrap techniques indicated that, even when a payer is unwilling to incur any additional cost for gains in effectiveness, the probability that clozapine is more cost-effective than usual care is at least 0.80. These findings were not as evident when outcomes where clozapine was not clearly superior (psychotic symptoms, weight gain) were examined. CONCLUSION: Clozapine demonstrated cost-effectiveness on some but not all measures of effectiveness when the alternative was a range of conventional antipsychotic medications.     

Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis

Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia, severe extrapyramidal side effects caused by other neuroleptics, or treatment-resistant psychosis. Fifty-five percent of all patients and 40% of schizophrenics improved with clozapine. Abnormal involuntary movements were suppressed during treatment and, with 1 exception, returned to baseline levels after clozapine was discontinued. Our results support the conclusion that clozapine's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents. The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring.     

Safety and effectiveness of low-dose clozapine in psychogeriatric patients: a preliminary study.

The short- and long-term treatment tolerance of low-dose clozapine was retrospectively investigated in 18 psychogeriatric patients. Discontinued use of the drug because of side effects or inefficiency was required for only four patients. In the long-term treatment group leukopenia was not observed, and disturbances of liver function appeared to be very infrequent. A second group of seven severely demented psychogeriatric inpatients who were currently being treated with low-dose clozapine underwent a withdrawal study in order to evaluate the therapeutic efficacy of the drug, measured by the NOSIE and the SCAG scales. The results indicate that for patients such as these, with paranoid or socially disturbing behavior who also tend to develop severe neurological side effects with classical neuroleptics, a low-dose administration of clozapine is an acceptable alternative treatment.     

Tolerability and therapeutic effect of clozapine. A retrospective investigation of 216 patients treated with clozapine for up to 12 years

Two hundred and sixteen psychiatric patients (183 men and 33 women) hospitalized in Sct. Hans Hospital were treated with clozapine between 1971-1983. All had been treated previously with one or more neuroleptic(s) and had either failed to respond adequately, or their response was limited by side effects. Eighty-five patients were treated exclusively with clozapine, while the remaining 131 received additional medication, mainly other neuroleptic drugs. The mean clozapine dosage was 317 mg/day (range 50-1200), and the mean duration of treatment was 23/4 years (range 1/12-12). The tolerability to clozapine was determined by an evaluation of haematological changes, pronounced side effects and mortality. One patient treated with clozapine (8 months) and nitrofurantoin (8 days) developed a reversible granulocytopenia. One patient (treated with a combination of drugs) had clinically insignificant depression of the leucocytes and three of segmented granulocytes. Seven had a reduction in thrombocytes. Two patients developed cardiac insufficiency, and four epileptic seizures. None of the patients treated exclusively with clozapine developed neurological side effects. A global estimation of therapeutic effect revealed that clozapine alone or in combination with other neuroleptic drugs was significantly better than previous antipsychotic therapy, although 47-63% of the patients showed no change. It is concluded that clozapine is a potent antipsychotic drug offering particular advantages in the treatment of schizophrenic patients with a pronounced symptomatology and tendency towards developing extrapyramidal side effects. Caution is advised in patients with cardiac insufficiency and epilepsy. There appears to be a slight risk of granulocytopenia, and therefore the present monitoring of WBC should continue in order to prevent this reaction and to obtain more complete information regarding risk of granulocytopenia.     

Klozapin. Status 1989

Clozapine is an atypical neuroleptic with two clinical advantages: it may improve otherwise treatment-resistant schizophrenic patients, and it does not induce extrapyramidal side effects or tardive dyskinesia. Pharmacologically, clozapine is a broad-spectrum neuroleptic that binds to several receptors (dopamine, noradrenaline, serotonin, histamine, and acetylcholine) but which has an exeptionally low binding to D-2 dopamine receptors and a relatively high binding to D-1 receptors as compared with traditional neuroleptics such as halo-peridol. Several controlled clinical trials have demonstrated that, compared with traditional neuroleptics, clozapine is a superior antipsychotic drug in the treatment of severe therapy-resistant schizophrenic patients. In doses up to 600 mg/day no extrapyramidal symptoms or tardive dyskinesia is seen, only some slowing of movements and reduced facial expression. Other side effects include sedation, hypersalivation, orthostatism, tachycardia, anticholinergic symptoms (especially constipation and, in elderly patients, confusion), weight gain, and blood dyscrasia. To ensure the regular control of leukocyte counts and differential together with ECG (weekly during the first month, later every half year), weight, and medication, a special monitoring form is used in most Danish psychiatric institutions. These forms may also be used as a “data bank” for nationwide surveys of the use of clozapine.