Botts Sheila, Littrell Robert, de Leon Jose
Mental Health Research Center at Eastern State Hospital, University of Kentucky, Lexington, KY 40508, USA.
J Clin Psychiatry. 2004 Aug;65(8):1138-43. doi: 10.4088/jcp.v65n0817.
Olanzapine has a U.S. Food and Drug Administration-approved dosing range of 10 to 20 mg/day but is often used at doses exceeding this range. Olanzapine is largely metabolized by cytochrome P450 (CYP) 1A2. Smoking, which induces CYP1A2, is expected to increase clearance of olanzapine by 40%; however, dosage adjustment in smokers is not currently recommended. Additionally, female gender is expected to reduce clearance by 30%. Many institutions target high-dose olanzapine prescribers in an effort to reduce unnecessary drug costs. However, factors such as smoking or gender may necessitate increased doses.
A retrospective review of all patients receiving olanzapine during an inpatient stay at a state psychiatric hospital in Kentucky during 2001 was conducted. Demographic information and smoking status were collected for all patients. Olanzapine doses of > 20 mg/day were considered high doses.
Nine percent (48/522) of olanzapine patients were prescribed high doses. The percentages were similar in women and men (10% vs. 9%, p =.69) and in smokers and nonsmokers (9% vs. 9%, p =.82). Moreover, the mean maximum olanzapine dose was also similar in men and women (15.4 +/- 7.2 vs. 14.9 +/- 7.3 mg/day, p =.51). The odds of receiving a high dose of olanzapine were increased 2.1 for patients with a schizophrenia spectrum diagnosis (DSM-IV schizophrenia or other psychotic disorder). The odds of receiving a high dose of olanzapine were increased with each incremental increase in length of stay (intermediate length of stay [8-60 days], OR = 5.6; long-term length of stay [> 60 days], OR = 12.0, relative to acute length of stay [< 8 days]).
Neither gender nor smoking status was associated with receiving a high dose of olanzapine. The association of increased length of stay with high dose suggests that treatment resistance may be an important factor in receiving high daily doses of olanzapine.
奥氮平在美国食品药品监督管理局批准的剂量范围为每日10至20毫克，但经常被用于超过此范围的剂量。奥氮平主要通过细胞色素P450（CYP）1A2代谢。吸烟可诱导CYP1A2，预计会使奥氮平的清除率提高40%；然而，目前不建议对吸烟者进行剂量调整。此外，女性预计会使清除率降低30%。许多机构将高剂量奥氮平的处方者作为目标，以努力降低不必要的药物成本。然而，吸烟或性别等因素可能需要增加剂量。
对2001年肯塔基州一家州立精神病医院住院期间接受奥氮平治疗的所有患者进行回顾性研究。收集了所有患者的人口统计学信息和吸烟状况。奥氮平剂量>20毫克/天被视为高剂量。
9%（48/522）的奥氮平患者被开具了高剂量处方。女性和男性的比例相似（10%对9%，p = 0.69），吸烟者和非吸烟者的比例也相似（9%对9%，p = 0.82）。此外，男性和女性的奥氮平平均最大剂量也相似（15.4±7.2对14.9±7.3毫克/天，p = 0.51）。精神分裂症谱系诊断（《精神疾病诊断与统计手册》第四版精神分裂症或其他精神障碍）患者接受高剂量奥氮平的几率增加2.1倍。住院时间每增加一次，接受高剂量奥氮平的几率就会增加（中等住院时间[8 - 60天]，比值比 = 5.6；长期住院时间[>60天]，比值比 = 12.0，相对于急性住院时间[<8天]）。
性别和吸烟状况均与接受高剂量奥氮平无关。住院时间延长与高剂量之间的关联表明，治疗抵抗可能是接受高剂量每日奥氮平治疗的一个重要因素。
