Goff D C, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner K D, Law C G, Ko G N
Psychotic Disorders Program, Massachusetts General Hospital, Boston, USA.
J Clin Psychopharmacol. 1998 Aug;18(4):296-304. doi: 10.1097/00004714-199808000-00009.
Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms.
根据《精神疾病诊断与统计手册第三版修订本》（DSM-III-R）标准，90例精神分裂症或分裂情感性障碍患者参与了这项双盲、探索性、剂量范围试验。在4至7天的单盲洗脱期后，患者被随机分配接受新抗精神病药物齐拉西酮4（N = 19）、10（N = 17）、40（N = 17）或160（N = 20）mg/天这四种固定剂量之一，或接受氟哌啶醇15 mg/天（N = 17），为期4周。齐拉西酮组之间建立了剂量-反应关系，用于改善临床总体印象严重程度（CGI-S）评分（p = 0.002），但在简明精神病评定量表（BPRS）总分方面未建立剂量-反应关系（p = 0.08）。对BPRS总分、BPRS精神病核心症状和CGI-S评分自基线的平均变化进行的意向性治疗分析表明，齐拉西酮160 mg/天在减轻总体精神病理学和阳性症状方面与氟哌啶醇相当，且优于齐拉西酮4 mg/天。尽管试验样本量小且持续时间短，但齐拉西酮160 mg/天和氟哌啶醇15 mg/天在CGI-S评分上的改善在统计学上均显著大于齐拉西酮4 mg/天（分别为p = 0.001和p = 0.005）。在齐拉西酮160 mg/天组中，BPRS总分（改善≥30%）和CGI-改善（评分1或2）量表上被归类为有反应者的患者百分比与氟哌啶醇组相似，且略高于齐拉西酮4 mg/天组，但差异无统计学意义。在所有临床疗效评估中，与齐拉西酮4 mg/天、10 mg/天和40 mg/天相关的改善相似。在研究期间的任何时候，同时使用苯海索的频率在齐拉西酮160 mg/天组（15%）低于氟哌啶醇组（53%）。与齐拉西酮不同，氟哌啶醇与持续性高催乳素血症相关，齐拉西酮仅观察到催乳素在给药间隔内短暂升高并恢复正常。齐拉西酮耐受性良好，所有组不良事件的发生率相似。本研究结果表明，齐拉西酮160 mg/天在减轻精神分裂症或分裂情感性障碍急性加重的总体精神病理学和阳性症状方面与氟哌啶醇15 mg/天一样有效，但诱发锥体外系症状的可能性较低。
