Kane John M
Department of Psychiatry, The Zucker Hillside Hospital of the North Shore Long Island Jewish Health System, Glen Oaks, NY 11004, USA.
J Clin Psychiatry. 2003;64 Suppl 19:19-25.
Pharmacotherapy of schizophrenia presents a set of challenges. Ideally, antipsychotic therapy should have a rapid effect on clinical improvement, show effectiveness against symptoms in multiple domains, and possess a tolerability profile that optimizes patient adherence and overall health outcomes. The atypical antipsychotic ziprasidone has been shown in placebo- and active-comparator-controlled clinical studies to be effective in treating the positive, negative, and affective symptoms of schizophrenia. In placebo-controlled trials of 4 to 6 weeks, significant improvements in overall psychopathology and negative symptoms as early as 1 week after treatment initiation were demonstrated. In trials of 4 to 8 weeks' duration in patients with acute exacerbation of schizophrenia, ziprasidone demonstrated efficacy comparable to that of haloperidol, olanzapine, and risperidone. In a 12-week study of patients with treatment-resistant schizophrenia, ziprasidone demonstrated overall efficacy comparable to that of chlorpromazine, with superior improvement in negative symptoms. In 6-week, open-label switching studies, patients switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone because of suboptimal efficacy or tolerability experienced improvement in symptoms. Oral ziprasidone's tolerability profile includes a lower movement disorder burden than that of risperidone, a lower liability for weight gain than that of risperidone or olanzapine, and an absence of significant deleterious effects on serum lipid levels or glucose metabolism. Available clinical data support rapid titration to > or = 120 mg/day for optimal efficacy in patients with acute exacerbation of schizophrenia.
精神分裂症的药物治疗面临一系列挑战。理想情况下，抗精神病药物治疗应能迅速改善临床症状，对多个领域的症状均显示出有效性，且具有良好的耐受性，以优化患者的依从性和整体健康状况。在安慰剂对照和活性对照的临床研究中，已证实非典型抗精神病药物齐拉西酮对治疗精神分裂症的阳性、阴性和情感症状有效。在为期4至6周的安慰剂对照试验中，治疗开始后仅1周，整体精神病理学和阴性症状就有显著改善。在精神分裂症急性加重患者中进行的为期4至8周的试验中，齐拉西酮显示出与氟哌啶醇、奥氮平和利培酮相当的疗效。在一项针对难治性精神分裂症患者的为期12周的研究中，齐拉西酮显示出与氯丙嗪相当的整体疗效，在阴性症状方面有更显著的改善。在为期6周的开放标签换药研究中，因疗效欠佳或耐受性问题从传统抗精神病药物、奥氮平或利培酮换用齐拉西酮的患者症状有所改善。口服齐拉西酮的耐受性表现为运动障碍负担低于利培酮，体重增加风险低于利培酮或奥氮平，且对血脂水平或葡萄糖代谢无显著有害影响。现有临床数据支持在精神分裂症急性加重患者中迅速滴定至≥120毫克/天以获得最佳疗效。
