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氯氮平的副作用。

Side effects of clozapine.

作者信息

Gaertner H J, Fischer E, Hoss J

机构信息

Psychiatrische Universitätsklinik, Tübingen, Federal Republic of Germany.

出版信息

Psychopharmacology (Berl). 1989;99 Suppl:S97-100. doi: 10.1007/BF00442570.

DOI:10.1007/BF00442570
PMID:2813671
Abstract

In addition to the low risk of agranulocytosis, several more frequent side effects are associated with clozapine therapy. We tried to estimate the incidence of these side effects. We analysed 391 treatments in 315 inpatients, who received clozapine alone or combined with other neuroleptic and antidepressant drugs. Two thirds were combined treatments, one third were treatments with clozapine alone (i.e., no other neuroleptic, antidepressant or anticonvulsive drugs were allowed). The numbers in brackets show the incidence based on the analysis of the treatments with clozapine alone. In 49% (61%) of the treatments a rise in the liver enzyme values was observed. However, counting only the cases in which a two-fold increase over the normal values was observed, the incidence was reduced to 20% (31%). Increase in temperature was observed in 4% (6%) and leukopenia (leukocyte count under 3500/microliters) was recorded in 2% (2%). Hypotensive dysregulation (systolic blood pressure under 90 mm Hg) was observed in 25% of all treatments and pharmacogenic delirium in 8%. No cases of agranulocytosis were observed. Mean treatment duration was 56 days, mean daily dosage 257 mg. The mean age of the patients was 34 years. In the overall evaluation 71% of the treatments were classified as successful; clozapine therapy was continued after discharge in 68% of the treatments. Adverse reactions (delirium, rise in temperature, hypotension, fatigue, rise in liver enzymes) necessitated a change of medication in 17% of the treatments. Changeover to another neuroleptic drug due to ineffectiveness of clozapine was necessary in 7% of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

除粒细胞缺乏症风险较低外,氯氮平治疗还伴有一些更常见的副作用。我们试图估算这些副作用的发生率。我们分析了315名住院患者的391次治疗情况,这些患者单独使用氯氮平或与其他抗精神病药物及抗抑郁药物联合使用。三分之二为联合治疗,三分之一为单独使用氯氮平治疗(即不允许使用其他抗精神病药物、抗抑郁药物或抗惊厥药物)。括号中的数字显示基于单独使用氯氮平治疗分析得出的发生率。在49%(61%)的治疗中观察到肝酶值升高。然而,仅计算肝酶值比正常值升高两倍的病例,发生率降至20%(31%)。4%(6%)的治疗中观察到体温升高,2%(2%)的治疗记录有白细胞减少(白细胞计数低于3500/微升)。25%的所有治疗中观察到低血压失调(收缩压低于90毫米汞柱),8%的治疗中有药源性谵妄。未观察到粒细胞缺乏症病例。平均治疗时长为56天,平均日剂量为257毫克。患者的平均年龄为34岁。在总体评估中,71%的治疗被归类为成功;68%的治疗出院后继续使用氯氮平治疗。17%的治疗因不良反应(谵妄、体温升高、低血压、疲劳、肝酶升高)需要更换药物。7%的治疗因氯氮平无效而需要换用另一种抗精神病药物。(摘要截断于250字)

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Side effects of clozapine.氯氮平的副作用。
Psychopharmacology (Berl). 1989;99 Suppl:S97-100. doi: 10.1007/BF00442570.
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[Frequent cases of agranulocytosis due to clozapin (leponex) in eastern Switzerland].
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本文引用的文献

1
Difficulties in assessing adverse drug reactions in clinical trials.评估临床试验中药物不良反应的困难。
Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(4-6):651-7. doi: 10.1016/s0278-5846(82)80162-0.
2
[Effects of neuroleptics on liver function, the hematopoietic system, blood pressure and temperature regulation. Comparison of clozapine, perazine and haloperidol by evaluating medical records].[抗精神病药物对肝功能、造血系统、血压及体温调节的影响。通过病历评估比较氯氮平、奋乃静和氟哌啶醇]
Pharmacopsychiatria. 1983 Jan;16(1):23-9. doi: 10.1055/s-2007-1017443.
3
Tolerability and therapeutic effect of clozapine. A retrospective investigation of 216 patients treated with clozapine for up to 12 years.
Treatment strategies for clozapine-induced hypotension: a systematic review.
氯氮平所致低血压的治疗策略:一项系统评价
Ther Adv Psychopharmacol. 2022 May 24;12:20451253221092931. doi: 10.1177/20451253221092931. eCollection 2022.
4
Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity.精神药物与肝脏疾病:药代动力学及肝脏毒性的批判性综述
World J Gastrointest Pharmacol Ther. 2017 Feb 6;8(1):26-38. doi: 10.4292/wjgpt.v8.i1.26.
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Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions.非典型抗精神病药物的肝脏安全性:当前证据与未来方向。
Drug Saf. 2016 Oct;39(10):925-43. doi: 10.1007/s40264-016-0436-7.
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An Unusual Case of Delirium after Restarting Clozapine.重新使用氯氮平后出现谵妄的罕见病例。
Clin Psychopharmacol Neurosci. 2016 Feb 29;14(1):107-8. doi: 10.9758/cpn.2016.14.1.107.
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Hepatotoxicity induced by clozapine: a case report and review of literature.氯氮平引起的肝毒性:病例报告及文献复习。
Neuropsychiatr Dis Treat. 2014 Aug 26;10:1585-7. doi: 10.2147/NDT.S67654. eCollection 2014.
8
Management of clozapine-induced fever in a child.儿童氯氮平所致发热的管理
Am J Psychiatry. 2014 Apr;171(4):398-402. doi: 10.1176/appi.ajp.2013.13070866.
9
Obsessive-compulsive symptoms in chronic schizophrenia: a new idea or an old belief?慢性精神分裂症中的强迫症状:新观点还是旧观念?
Indian J Psychiatry. 1997 Oct;39(4):324-8.
10
Subtype specificity of gamma-aminobutyric acid type A receptor antagonism by clozapine.氯氮平对γ-氨基丁酸A型受体拮抗作用的亚型特异性
Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):365-73. doi: 10.1007/BF00172773.
氯氮平的耐受性与治疗效果。对216例接受氯氮平治疗长达12年的患者进行的回顾性调查。
Acta Psychiatr Scand. 1985 Feb;71(2):176-85. doi: 10.1111/j.1600-0447.1985.tb01268.x.
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[Studies of the side effect profile of clozapine].[氯氮平副作用概况的研究]
Psychiatr Neurol Med Psychol (Leipz). 1986 Mar;38(3):148-52.
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Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis.氯氮平治疗迟发性运动障碍、抗精神病药敏感性及难治性精神病的疗效
J Clin Psychiatry. 1987 Jul;48(7):263-7.
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Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison.氯氮平、氯丙嗪与安慰剂用于新入院急性精神分裂症患者的对照双盲比较
Arch Gen Psychiatry. 1979 Jun;36(6):657-64. doi: 10.1001/archpsyc.1979.01780060047005.