Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands.
Oncologist. 2020 Mar;25(3):e570-e577. doi: 10.1634/theoncologist.2019-0470. Epub 2019 Dec 8.
Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer.
Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress.
Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31-59) for olanzapine and 57% (95% CI, 43-71) for haloperidol (Δ DRR -12%; odds ratio [OR], 0.61; 95% CI, 0.2-1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2-5.9 days) for olanzapine and 2.8 days (95% CI, 1.9-3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility.
Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559.
Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.
治疗谵妄通常包括氟哌啶醇。奥氮平等第二代抗精神病药已作为一种可能副作用较少的替代药物出现。这项多中心、III 期、随机临床试验的目的是比较奥氮平和氟哌啶醇治疗晚期癌症住院患者谵妄的疗效和耐受性。
符合条件的成年患者（≥18 岁）患有晚期癌症和谵妄（修订后的谵妄评定量表-98 [DRS-R-98] 总分≥17.75）按 1:1 随机接受氟哌啶醇或奥氮平（年龄调整，可滴定剂量）治疗。主要终点是谵妄反应率（DRR），定义为 DRS-R-98 严重程度评分<15.25 和≥4.5 分降低的患者人数。次要终点包括反应时间（TTR）、耐受性和谵妄相关的困扰。
2011 年 1 月至 2016 年 6 月，共有 98 名患者纳入意向治疗分析。奥氮平的 DRR 为 45%（95%置信区间 [CI]，31-59），氟哌啶醇为 57%（95% CI，43-71）（DRR 差值-12%；优势比 [OR]，0.61；95% CI，0.2-1.4；p=0.23）。奥氮平的平均 TTR 为 4.5 天（95% CI，3.2-5.9 天），氟哌啶醇为 2.8 天（95% CI，1.9-3.7 天；p=0.18）。奥氮平和氟哌啶醇组分别有 5 名（10.2%）和 10 名（20.4%）患者发生≥3 级与治疗相关的不良事件。两组的困扰率相似。由于无效，该研究提前终止。
与氟哌啶醇相比，奥氮平治疗晚期癌症住院患者的谵妄并没有改善 DRR 或 TTR。临床试验识别号。NCT01539733。荷兰试验登记处。NTR2559。
指南建议，成人癌症患者谵妄治疗的药物干预应限于有明显谵妄症状的患者。有人建议，与氟哌啶醇相比，非典型抗精神病药，如奥氮平，在疗效和安全性方面更具优势。然而，比较癌症患者典型与非典型抗精神病药疗效和安全性的综合数据有限。如果考虑针对晚期癌症患者的谵妄进行有针对性和明智的使用抗精神病药物，本研究表明，氟哌啶醇或奥氮平的反应没有统计学上的显著差异。奥氮平与氟哌啶醇相比总体具有更好的安全性，但这一差异无统计学意义。
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