Citrome Leslie
Department of Psychiatry, New York University School of Medicine, and the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
J Clin Psychiatry. 2007 Dec;68(12):1876-85. doi: 10.4088/jcp.v68n1207.
To compare the efficacy and safety of the intramuscular formulations of ziprasidone, olanzapine, and aripiprazole in treating agitation.
The pivotal registration trials were accessed by querying on-line literature and clinical trial databases. Pharmacovigilance data and posters were requested from the manufacturers. No date or language constraints were applied.
Nine double-blind, randomized, controlled clinical trials were identified.
Number needed to treat (NNT) for response to treatment for agitation and number needed to harm (NNH) for extrapyramidal effects were calculated from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labeling.
Using the a priori definitions of response at 2 hours after the first injection, NNT for response versus placebo (or placebo equivalent) in treating agitation for the pooled data at the recommended dose of ziprasidone 10-20 mg was 3 (95% CI = 2 to 4), for olanzapine 10 mg was 3 (95% CI = 2 to 3), and for aripiprazole 9.75 mg was 5 (95% CI = 4 to 8). Treatment-emergent adverse events occurring during the pivotal trials revealed statistically significant NNH versus placebo (or placebo equivalent) for aripiprazole for headache (NNH = 20, 95% CI = 11 to 170) and nausea (NNH = 17, 95% CI = 11 to 38), for ziprasidone in the treatment of headache (NNH = 15, 95% CI = 8 to 703), and for olanzapine in treatment-emergent hypotension (NNH = 50, 95% CI = 30 to 154). Olanzapine and aripiprazole had a more favorable extrapyramidal side effect profile compared to haloperidol. (There was no haloperidol treatment arm in the ziprasidone studies.)
Although the lowest NNT, and hence strongest therapeutic effect, was seen for the studies of ziprasidone and olanzapine as opposed to aripiprazole, head-to-head controlled studies directly comparing these 3 agents are needed.
比较齐拉西酮、奥氮平和阿立哌唑的肌内注射制剂治疗激越的疗效和安全性。
通过查询在线文献和临床试验数据库获取关键注册试验资料。向制造商索取药物警戒数据和海报。未设定日期或语言限制。
确定了9项双盲、随机、对照临床试验。
根据研究报告计算治疗激越的治疗有效率所需治疗人数（NNT）和锥体外系反应的伤害所需治疗人数（NNH）。通过产品标签获取其他需进行NNH分析的安全性结果。
根据首次注射后2小时的反应先验定义，齐拉西酮推荐剂量10 - 20 mg时，治疗激越的合并数据中，与安慰剂（或等效安慰剂）相比的反应NNT为3（95%CI = 2至4），奥氮平10 mg时为3（95%CI = 2至3），阿立哌唑9.75 mg时为5（95%CI = 4至8）。关键试验期间出现的治疗中出现的不良事件显示，阿立哌唑的头痛（NNH = 20，95%CI = 11至170）和恶心（NNH = 17，95%CI = 11至38）、齐拉西酮治疗头痛（NNH = 15，95%CI = 8至703）以及奥氮平治疗中出现的低血压（NNH = 50，95%CI = 30至154）与安慰剂（或等效安慰剂）相比具有统计学显著差异。与氟哌啶醇相比，奥氮平和阿立哌唑的锥体外系副作用较小。（齐拉西酮研究中没有氟哌啶醇治疗组。）
虽然与阿立哌唑相比，齐拉西酮和奥氮平研究的NNT最低，因此治疗效果最强，但仍需要直接比较这3种药物的头对头对照研究。
