Citrome Leslie, Yang Ruoyong, Glue Paul, Karayal Onur N
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
Schizophr Res. 2009 Jun;111(1-3):39-45. doi: 10.1016/j.schres.2009.03.009. Epub 2009 Apr 17.
Higher dose ziprasidone has been associated with improved treatment outcomes in patients with schizophrenia or schizoaffective disorder. This study examines the relationship of ziprasidone dose and all-cause discontinuation in randomized clinical trials in patients with an acute exacerbation of schizophrenia or schizoaffective disorder.
Data were analyzed for the first 28 days from 4 pivotal, randomized, double-blind, fixed-dose ziprasidone trials. Patients in these trials had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder where ziprasidone was administered twice daily with food. Data were analyzed to examine the association between ziprasidone dose and all-cause discontinuation due to lack of efficacy, adverse events, or because of other reasons, relative to placebo. Differences in discontinuation were evaluated using Cox proportional hazard models and number needed to treat (NNT).
All-cause discontinuation for ziprasidone ranged from a low of 26.9% for the 160 mg/d dose group, to 40.9% for the 40 mg/d and 45.5% for the 80 mg/d groups, compared with 49.5% for placebo. The NNTs for avoiding 1 additional all-cause discontinuation compared with placebo were 12 (40 mg/d; n=186), 25 (80 mg/d; n=154), 9 (120 mg/d; n=125), and 4 (160 mg/d; n=104). The 120 mg/d and 160 mg/d groups were the only ziprasidone regimens associated with significantly lower all-cause discontinuation rates versus placebo in both the survival analysis (p=0.031 and <0.0001, respectively) and in examination of the NNT. The 160 mg/d group was associated with lower all-cause discontinuation rates versus lower-dose ziprasidone regimens (p=0.0158 for versus 40 mg/d, p=0.002 for versus 80 mg/d). Efficacy accounted for 51% of all medication discontinuations across ziprasidone groups, compared with 62% for placebo. Findings for overall discontinuation due to lack of efficacy are consistent with results for all-cause discontinuation.
Consistent with previous reports, higher doses of ziprasidone (120-160 mg/d, dosed twice daily with meals) are associated with significantly lower all-cause discontinuation rates and more favorable NNTs versus placebo. This was primarily driven by lower rates of discontinuation due to lack of efficacy.
在精神分裂症或分裂情感性障碍患者中，较高剂量的齐拉西酮与改善治疗结局相关。本研究在精神分裂症或分裂情感性障碍急性加重患者的随机临床试验中，考察了齐拉西酮剂量与全因停药之间的关系。
对4项关键的、随机、双盲、固定剂量齐拉西酮试验的前28天数据进行分析。这些试验中的患者符合DSM-IV精神分裂症或分裂情感性障碍诊断标准，齐拉西酮每日两次与食物同服。分析数据以考察齐拉西酮剂量与因疗效不佳、不良事件或其他原因导致的全因停药之间的关联，并与安慰剂进行比较。使用Cox比例风险模型和需治疗人数（NNT）评估停药差异。
齐拉西酮的全因停药率范围为：160mg/d剂量组低至26.9%，40mg/d组为40.9%，80mg/d组为45.5%，而安慰剂组为49.5%。与安慰剂相比，避免再出现1例全因停药的NNT分别为：12（40mg/d；n = 186）、25（80mg/d；n = 154）、9（120mg/d；n = 125）和4（160mg/d；n = 104）。在生存分析（分别为p = 0.031和<0.0001）以及NNT分析中，120mg/d和160mg/d组是仅有的与安慰剂相比全因停药率显著更低的齐拉西酮治疗方案。与低剂量齐拉西酮治疗方案相比，160mg/d组全因停药率更低（与40mg/d组相比p = 0.0158，与80mg/d组相比p = 0.002）。在齐拉西酮各治疗组中，因疗效不佳导致的停药占所有药物停药的51%，而安慰剂组为62%。因疗效不佳导致的总体停药结果与全因停药结果一致。
与之前的报告一致，较高剂量的齐拉西酮（120 - 160mg/d，每日两次与餐同服）与显著更低的全因停药率以及相比安慰剂更有利的NNT相关。这主要是由于因疗效不佳导致的停药率较低。
