Effect size of symptom status in withdrawal of typical antipsychotics and subsequent clozapine treatment in patients with treatment-resistant schizophrenia.
Effect size of symptom status in withdrawal of typical antipsychotics and subsequent clozapine treatment in patients with treatment-resistant schizophrenia.
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对于难治性精神分裂症患者，症状状态对戒断典型抗精神病药物和随后的氯氮平治疗的影响大小。
DOI：
10.1176/appi.ajp.160.6.1133
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Bartko,JohnJ
中科院分区：
文献类型：
--
作者：
Pickar,David;Bartko,JohnJ
目的考虑到新型抗精神病药物的疗效以及停药可能对后续药物反应产生负面影响，在精神分裂症研究中使用安慰剂可能是不道德的。本研究考察安慰剂洗脱期症状加重的效应大小，以及洗脱期对后续药物治疗效果的影响。方法对某研究单位收治的50例难治性精神分裂症患者进行双盲纵向研究，观察慢性典型抗精神病药物治疗后和前瞻性氯氮平治疗前的药物洗脱效果。分析简要精神病学评定量表（BPRS）评分，以检查基线治疗典型抗精神病药（治疗6个月）、安慰剂药物洗脱期（平均34天）、早期氯氮平治疗（平均42天，平均剂量=345.0 mg/天）和最佳氯氮平治疗（平均83天，平均剂量=450.5 mg/天）的药物效应和效应大小。结果：与基线治疗相比，安慰剂洗脱期患者的BPRS总分、阳性和阴性症状评分显著升高，而与安慰剂洗脱期和基线治疗相比，给予氯氮平组患者的BPRS总分显著降低。然而，30%的患者在安慰剂洗脱期症状有所改善。基线治疗与安慰剂洗脱相比，BPRS总分的效应量为0.63，最佳氯氮平治疗与安慰剂洗脱相比为1.10，最佳氯氮平治疗与基线治疗相比为0.82。结论难治性精神分裂症患者停药后症状加重不影响其对氯氮平的反应性。与典型抗精神病药物相比，氯氮平的效应量表明，药物洗脱纵向设计对于建立无药物基线和调查药物反应是有用的，同时需要相对较少的受试者。
OBJECTIVEIn light of the efficacy of newer antipsychotic agents and the possibility that drug withdrawal may negatively affect subsequent drug response, concern has arisen that the use of placebo in schizophrenia research may be unethical. This study examines the effect size of symptom exacerbation during drug washout with placebo and the effects of drug washout on the efficacy of subsequent drug treatment.METHODFifty patients with treatment-resistant schizophrenia hospitalized on a research unit participated in a double-blind longitudinal study of the effects of drug washout after chronic treatment with a typical antipsychotic and before prospective treatment with clozapine. Brief Psychiatric Rating Scale (BPRS) scores were analyzed to examine drug effects and effect sizes for baseline treatment with a typical antipsychotic (>6 months treatment), drug washout with placebo (mean=34 days), early treatment with clozapine (mean=42 days, mean dose=345.0 mg/day), and optimal clozapine treatment (mean=83 days, mean dose=450.5 mg/day).RESULTSPatients’ BPRS total, positive, and negative symptom scores significantly increased during placebo washout, compared with baseline treatment, and significantly decreased with administration of clozapine, compared with placebo washout and baseline treatment. However, 30% of patients showed some symptom improvement during placebo washout. The effect sizes for the BPRS total score were 0.63 for baseline treatment versus placebo washout, 1.10 for optimal clozapine treatment versus placebo washout, and 0.82 for optimal clozapine treatment versus baseline treatment.CONCLUSIONSSymptom exacerbation induced by drug withdrawal in patients with treatment-resistant schizophrenia did not impede subsequent responsiveness to clozapine. The effect size for clozapine, compared with typical antipsychotics, suggests that the drug-washout longitudinal design is useful for establishing a drug-free baseline and for investigating drug response, while requiring relatively few subjects.