Wright Padraig, Meehan Karena, Birkett Martin, Lindborg Stacy R, Taylor Cindy C, Morris Philip, Breier Alan
Lilly Research Centre, Eli Lilly and Co. Ltd., Surrey, United Kingdom.
Clin Ther. 2003 May;25(5):1420-8. doi: 10.1016/s0149-2918(03)80129-7.
Acutely agitated patients with schizophrenia who receive intramuscular (IM) medications typically are switched to oral (PO) antipsychotic maintenance therapy.
The goal of this study was to assess the efficacy and safety of olanzapine versus those of haloperidol during transition from IM to PO therapy. We used additional data from a previously reported trial to test the hypothesis that the reduction in agitation achieved by IM olanzapine 10 mg or IM haloperidol 7.5 mg would be maintained following transition to 4 days of PO olanzapine or PO haloperidol (5-20 mg/d for both). We also hypothesized that olanzapine would maintain its more favorable extrapyramidal symptom (EPS) safety profile.
This was a multinational (hospitals in 13 countries), double-blind, randomized, controlled trial. Acutely agitated inpatients with schizophrenia were treated with 1 to 3 IM injections to olanzapine 10 mg or haloperidol 7.5 mg over 24 hours and were entered into a 4-day PO treatment period with the same medication (5-20 mg/d for both). The primary efficacy measurement was reduction in agitation, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score. Adverse events and scores on EPS rating scales were assessed.
A total of 311 patients (204 men, 107 women; mean [SD] age, 38.2 [11.6] years) were enrolled (131, 126, and 54 patients in the olanzapine, haloperidol, and placebo groups, respectively). In all, 93.1% (122/131) of olanzapine-treated patients and 92.1% (116/126) of haloperidol-treated patients completed the IM period and entered the PO period; 85.5% (112/131) of olanzapine-treated patients and 84.1% (106/126) of haloperidol-treated patients completed the PO period. IM olanzapine and IM haloperidol effectively reduced agitation over 24 hours (mean [SD] PANSS-EC change, -7.1 [4.81 vs -6.7 [4.3], respectively). Reductions in agitation were sustained throughout the PO period with both study drugs (mean [SD] change from PO period baseline, -0.6 [4.8] vs -1.3 [4.4], respectively). During PO treatment, haloperidol-treated patients spontaneously reported significantly more acute dystonia than olanzapine-treated patients (4.3%[5/116] vs 0% [0/122], respectively; P = 0.026) and akathisia (5.2% [6/116] vs 0% [0/122], respectively; P = 0.013). Significantly more haloperidol-treated patients than olanzapine-treated patients met categorical criteria for treatment-emergent akathisia (18.5% [17/92] vs 6.5% [7/107], respectively; P = 0.015).
In the acutely agitated patients with schizophrenia in this study, both IM olanzapine 10 mg and IM haloperidol 7.5 mg effectively reduced agitation over 24 hours. This alleviation of agitation was sustained following transition from IM therapy to 4 days of PO treatment (5-20 mg/d for both). During the 4 days of PO treatment, olanzapine-treated patients did not spontaneously report any incidences of acute dystonia, and olanzapine had a superior EPS safety profile to that of haloperidol. The combination of IM and PO olanzapine may help improve the treatment of acutely agitated patients with schizophrenia.
接受肌内注射（IM）药物治疗的急性激越型精神分裂症患者通常会转换为口服（PO）抗精神病药物维持治疗。
本研究的目的是评估奥氮平与氟哌啶醇在从IM治疗转换为PO治疗期间的疗效和安全性。我们使用了先前报道试验的额外数据，以检验以下假设：在转换为4天的PO奥氮平或PO氟哌啶醇（两者均为5 - 20mg/d）治疗后，肌内注射10mg奥氮平或7.5mg氟哌啶醇所实现的激越减轻情况将得以维持。我们还假设奥氮平将维持其更有利的锥体外系症状（EPS）安全性。
这是一项跨国（13个国家的医院）、双盲、随机、对照试验。急性激越型精神分裂症住院患者在24小时内接受1至3次肌内注射，给予10mg奥氮平或7.5mg氟哌啶醇，并进入为期4天的相同药物PO治疗期（两者均为5 - 20mg/d）。主要疗效测量指标是通过阳性和阴性症状量表 - 激越分量表（PANSS - EC）评分来衡量的激越减轻情况。评估不良事件和EPS评定量表评分。
共纳入311例患者（204例男性，107例女性；平均[标准差]年龄，38.2[11.6]岁）（奥氮平组、氟哌啶醇组和安慰剂组分别为131例、126例和54例患者）。总体而言，93.1%（122/131）的奥氮平治疗患者和92.1%（116/126）的氟哌啶醇治疗患者完成了IM期并进入PO期；85.5%（112/131）的奥氮平治疗患者和84.1%（106/126）的氟哌啶醇治疗患者完成了PO期。肌内注射奥氮平和肌内注射氟哌啶醇在24小时内均有效减轻激越（平均[标准差]PANSS - EC变化分别为 - 7.1[4.8]和 - 6.7[4.3]）。两种研究药物在整个PO期均维持了激越的减轻（从PO期基线起的平均[标准差]变化分别为 - 0.6[4.8]和 - 1.3[4.4]）。在PO治疗期间，氟哌啶醇治疗的患者自发报告的急性肌张力障碍明显多于奥氮平治疗的患者（分别为4.3%[5/116]对0%[0/122]；P = 0.026）和静坐不能（分别为5.2%[6/116]对0%[0/122]；P = 0.013）。达到治疗中出现的静坐不能分类标准的氟哌啶醇治疗患者明显多于奥氮平治疗患者（分别为18.5%[17/92]对6.5%[7/107]；P = 0.015）。
在本研究的急性激越型精神分裂症患者中，肌内注射10mg奥氮平和肌内注射7.5mg氟哌啶醇在24小时内均有效减轻激越。从IM治疗转换为4天的PO治疗（两者均为5 - 20mg/d）后，这种激越减轻情况得以维持。在4天的PO治疗期间，奥氮平治疗的患者未自发报告任何急性肌张力障碍事件，且奥氮平的EPS安全性优于氟哌啶醇。肌内注射和口服奥氮平联合使用可能有助于改善急性激越型精神分裂症患者的治疗。
