Variables Associated With High Olanzapine Dosing in a State Hospital

Sheila Botts, Pharm.D.; Robert Littrell, Pharm.D.; and Jose de Leon, M.D.

Background: 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.

Method: 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.

Results: 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]).

Conclusions: 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.

(J Clin Psychiatry 2004;65:1138-1143)

Received June 4, 2003; accepted Jan. 21, 2004. From the Mental Health Research Center at Eastern State Hospital (Drs. Botts and de Leon); the Division of Pharmacy Practice and Science, College of Pharmacy (all authors); the Department of Psychiatry, College of Medicine (Dr. de Leon); and the Research and Data Management Center (Drs. Botts and Littrell), University of Kentucky, Lexington.

The data collection for this study was supported by internal resources, and no pharmaceutical company provided any support for this study.

A preliminary version of this article was presented as an abstract at the American College of Clinical Pharmacy Spring Practice and Research Forum/Update in Therapeutics, April 27-30, 2003, Palm Springs, Calif.

Dr. Botts has recently submitted a researcher-initiated proposal to Eli Lilly Research Foundation. During the last 2 years, Dr. Botts has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen. During the last 2 years, Dr. Littrell has served as a consultant for Janssen and on the speakers bureaus of Janssen and Bristol-Myers Squibb. During the last 2 years, Dr. de Leon has been on the advisory boards of Bristol-Myers Squibb and AstraZeneca, received researcher-initiated grants from Eli Lilly Research Foundation and Roche Molecular Systems, Inc, and once delivered a lecture supported by Eli Lilly.

Corresponding author and reprints: Jose de Leon, M.D., Mental Health Research Center at Eastern State Hospital, 627 W. Fourth St., Lexington, KY 40508 (e-mail: jdeleon@uky.edu).