Wahlbeck K, Cheine M, Essali A, Adams C
Department of Psychiatry, University of Helsinki, Finland.
Am J Psychiatry. 1999 Jul;156(7):990-9. doi: 10.1176/ajp.156.7.990.
The purpose of this study was to evaluate all available trial-based evidence on the effectiveness of clozapine in schizophrenia as compared with conventional neuroleptics.
All randomized, controlled trials comparing clozapine with a conventional neuroleptic in which there was satisfactory concealment of patients' treatment allocation were located through electronic searches in all languages of several databases and through contacting authors of recent trials as well as the manufacturer of clozapine. At least two independent reviewers assessed trials for inclusion in the study and extracted data for meta-analysis.
The review included 2,530 randomly assigned participants in 30 trials, most of them short-term. Clozapine-treated patients showed more clinical improvement and experienced significantly fewer relapses during treatment, although the risk of blood dyscrasias in long-term treatment may be as high as 7%. Scores on symptom rating scales showed greater improvement among clozapine-treated patients, who were also more satisfied with their treatment. However, there was no evidence that the superior clinical effect of clozapine is reflected in levels of functioning; on the other hand, global functional and pragmatic outcomes were frequently not reported. Clinical improvement was most pronounced in patients with treatment-resistant illness.
This meta-analysis confirms that clozapine is more effective than conventional neuroleptics in reducing symptoms of patients with both treatment-resistant and nonresistant schizophrenia. Future trials should be long-term pragmatic community trials or should address the effectiveness of clozapine in special patient populations. An international standard set of outcomes, including pragmatic assessments of functioning, would greatly enhance the comparison and summation of trials and future assessments of effectiveness.
本研究旨在评估与传统抗精神病药物相比，氯氮平治疗精神分裂症有效性的所有基于试验的现有证据。
通过对多个数据库的所有语言进行电子检索，以及联系近期试验的作者和氯氮平制造商，找出所有将氯氮平与传统抗精神病药物进行比较且患者治疗分配隐匿良好的随机对照试验。至少两名独立评审员评估试验是否纳入本研究，并提取数据进行荟萃分析。
该综述纳入了30项试验中的2530名随机分配参与者，其中大多数为短期试验。接受氯氮平治疗的患者临床改善更明显，治疗期间复发显著减少，尽管长期治疗中血液系统疾病的风险可能高达7%。症状评定量表评分显示，接受氯氮平治疗的患者改善更大，他们对治疗也更满意。然而，没有证据表明氯氮平的卓越临床效果体现在功能水平上；另一方面，总体功能和实际结果经常未被报告。治疗抵抗性疾病患者的临床改善最为显著。
这项荟萃分析证实，氯氮平在减轻治疗抵抗性和非抵抗性精神分裂症患者症状方面比传统抗精神病药物更有效。未来的试验应该是长期的实际社区试验，或者应该关注氯氮平在特殊患者群体中的有效性。一套国际标准的结果，包括对功能的实际评估，将大大加强试验的比较和汇总以及未来有效性评估。
