Eli Lilly and Company, Indianapolis, IN, USA.
BMC Psychiatry. 2012 May 30;12:51. doi: 10.1186/1471-244X-12-51.
To treat acute schizophrenia, a long-acting injectable antipsychotic needs a rapid onset of action and therapeutic profile similar to that of oral agents. The present post-hoc analyses compared results from a randomized, double-blind, placebo-controlled trial of olanzapine long-acting injection (LAI) for acute schizophrenia with those observed in similarly designed trials of oral olanzapine.
Six-week results from the olanzapine LAI study (N = 404) were compared with those of 3 oral studies (study 1: olanzapine vs. haloperidol vs. placebo [N = 335]; study 2: olanzapine vs. haloperidol vs. low-dose olanzapine [N = 431]; study 3: olanzapine vs. placebo vs. low-dose olanzapine [N = 152]). All patients had baseline Brief Psychiatric Rating Scale (BPRS) scores ≥24 (0-6 scale). Six-week effect sizes were calculated. Efficacy onset, pharmacokinetics, discontinuations, weight gain, and extrapyramidal symptoms were also assessed.
At 6 weeks, mean BPRS scores decreased by 14 to 15 points for olanzapine LAI (405 mg/4 weeks, 210 or 300 mg/2 weeks), by 8 to 16 for oral olanzapine (10 ± 2.5 or 15 ± 2.5 mg/day), and by 12 to 13 for haloperidol (15 ± 5 mg/day). For those same dose groups, effect sizes vs. placebo for the BPRS were 0.7 to 0.8 for olanzapine LAI, 0.5 to 0.7 for oral olanzapine, and 0.6 for haloperidol. The first statistically significant separation from placebo on the BPRS occurred at 3 days for the olanzapine LAI groups and at 1 week for oral olanzapine and haloperidol (15 ± 5 mg/day) in oral study 1 although as late as week 6 for the 10-mg/day olanzapine dose in oral study 3. Olanzapine concentrations were similar across studies. Weight gain ≥7% of baseline occurred in up to 35% of olanzapine LAI and oral patients versus up to 12% of haloperidol and placebo patients. Extrapyramidal symptoms were lowest in the olanzapine LAI groups and significantly greater in the haloperidol groups. No post-injection delirium/sedation syndrome events occurred in the olanzapine LAI study.
Patients treated acutely with olanzapine LAI showed a similar pattern of improvement to that seen historically with oral olanzapine. With the exception of injection-related adverse events, the efficacy and tolerability profile of olanzapine LAI is similar to oral olanzapine.
ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00088478; ClinicalStudyResults.org ID; URL: http://www.clinicalstudyresults.org/: 917, 978, 982, and 5984.
为了治疗急性精神分裂症，长效注射抗精神病药需要迅速起效，并具有与口服药物相似的治疗特征。本事后分析比较了奥氮平长效注射剂（LAI）治疗急性精神分裂症的随机、双盲、安慰剂对照试验（N=404）的结果与类似设计的奥氮平口服研究（研究 1：奥氮平 vs. 氟哌啶醇 vs. 安慰剂 [N=335]；研究 2：奥氮平 vs. 氟哌啶醇 vs. 低剂量奥氮平 [N=431]；研究 3：奥氮平 vs. 安慰剂 vs. 低剂量奥氮平 [N=152]）的结果。所有患者基线Brief Psychiatric Rating Scale（BPRS）评分均≥24（0-6 分）。计算了 6 周的疗效大小。还评估了起效时间、药代动力学、停药、体重增加和锥体外系症状。
在 6 周时，奥氮平 LAI（405mg/4 周、210 或 300mg/2 周）、口服奥氮平（10±2.5 或 15±2.5mg/天）和氟哌啶醇（15±5mg/天）的 BPRS 评分平均降低 14-15 分。对于相同剂量组，奥氮平 LAI 与安慰剂相比，BPRS 的疗效大小为 0.7-0.8，口服奥氮平为 0.5-0.7，氟哌啶醇为 0.6。奥氮平 LAI 组首次与安慰剂在 BPRS 上有统计学意义的分离发生在第 3 天，而口服奥氮平组和氟哌啶醇（15±5mg/天）在口服研究 1 中为第 1 周（尽管在口服研究 3 中，奥氮平 10mg/天组直到第 6 周）。奥氮平浓度在各研究中相似。体重增加≥基线的 7%发生在高达 35%的奥氮平 LAI 和口服患者中，而氟哌啶醇和安慰剂患者中高达 12%。锥体外系症状在奥氮平 LAI 组最低，在氟哌啶醇组显著更高。奥氮平 LAI 研究中未发生注射后谵妄/镇静综合征事件。
急性接受奥氮平 LAI 治疗的患者表现出与历史上口服奥氮平相似的改善模式。除了与注射相关的不良事件外，奥氮平 LAI 的疗效和耐受性与口服奥氮平相似。
ClinicalTrials.gov ID；网址：http://http//www.clinicaltrials.gov/: NCT00088478；ClinicalStudyResults.org ID；网址：http://www.clinicalstudyresults.org/: 917、978、982 和 5984。
