奥氮平治疗恶心、谵妄、焦虑、失眠和恶病质的证据汇总
奥氮平属于第二代非典型抗精神病药物，临床上常被超说明书用于治疗成人恶心、谵妄、焦虑、失眠和恶病质。因此，姑息治疗的临床医生可以利用它来缓解他们患者的多种症状。本文将审查奥氮平超说明书使用的药理学和可用证据。
药理学：奥氮平具有独特的作用受体，拮抗中枢神经系统多巴胺受体（治疗恶心、谵妄），抑制5-HT2受体（失眠、焦虑、恶病质有关）及抗胆碱能作用[1-3]。达峰时间约为6小时，终末消除半衰期21-54小时[4]。
不良反应和注意事项：与其他抗精神病药相比，奥氮平较少引起锥体外系症状[5]，对QTc间期的影响小于氟哌啶醇[6]，但嗜睡[7]和体重增加[8-10]的不良反应较明显。此外，奥氮平与口干、高血糖症、水肿以及老年痴呆患者的死亡率有关。肾或肝损害的患者无需调整剂量，肝病终末期谨慎使用。
恶心：两个病例报告和一项回顾性试验研究了奥氮平对慢性恶心、呕吐的疗效，平均剂量5mg/d[12,13]。在一项开放性标签研究中，晚期癌症患者接受奥氮平2.5mg-10mg，生活质量显著改善，恶心症状缓解[14]。对于化疗引起的恶心和呕吐（CINV），许多有力的证据支持奥氮平的疗效[15]。一项双盲随机对照试验表明，奥氮平对于CINV的治疗要优于胃复安（无呕吐比例70%vs31%，a number-needed-to-treat of 2.5）[16]。
谵妄：奥氮平对谵妄的疗效已被证明与氟哌啶醇相当。剂量范围为2.5mg-10mg/d，最大剂量可达20mg/d[17]。一项针对晚期癌症患者的开放标签初步研究发现，37%的患者对奥氮平(5mg-10mg/d)治疗有响应[18]。在另一项前瞻性开放试验中，79例癌症住院患者服用奥氮平治疗谵妄，结果76%的患者症状完全缓解[19]。
焦虑：奥氮平已被研究用于难治性焦虑症（GAD）。在一项随机安慰剂对照试验中，氟西汀单药治疗效果不佳的GAD患者添加奥氮平或安慰剂，结果发现，奥氮平（平均剂量8.7mg/d）疗效优于安慰剂[20]。
失眠：奥氮平（初始最小剂量2.5mg）辅助SSRI可以提高抑郁症患者的睡眠效率、改善睡眠质量[21]。此外，还有研究发现，单剂量10mg奥氮平能够增加慢波睡眠及总睡眠时间[3]。
恶病质：奥氮平已被研究用于慢性疾病如癌症相关的恶病质治疗。奥氮平5mg/d辅助醋酸甲地孕酮治疗，能显著刺激患者食欲，增加体重[22]。在一项开放标签研究中，奥氮平2.5-20mg单药治疗能够减弱晚期癌症患者的体重减轻现象[23]。
证据表明，奥氮平对于化疗所致的恶心和呕吐具有一定的疗效，还对谵妄、焦虑、失眠、恶病质同样有效。然而，由于其治疗成本和长期护理中的潜在障碍，姑息治疗的临床医生要充分权衡，谨慎对待这些超说明书使用。
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