Mental Health-Clinical Research Center, Department of Psychiatry, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242-1057, USA.
Biol Psychiatry. 2010 Feb 1;67(3):255-62. doi: 10.1016/j.biopsych.2009.08.040. Epub 2009 Nov 7.
A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study.
Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year.
All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity.
By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure.
比较不同药物剂量的标准化定量方法是设计临床试验和检查长期药物副作用(如迟发性运动障碍)影响的有用工具。这种方法需要建立剂量当量。一个专家共识小组已经为第一代和第二代抗精神病药物发布了各种抗精神病药物等效剂量图表。本研究使用了这些图表。
回归用于比较专家图表中的每种药物与氯丙嗪和氟哌啶醇,并为每种关系创建公式。为氯丙嗪 100mg 和氟哌啶醇 2mg 求解公式,得出新的氯丙嗪和氟哌啶醇当量。将公式纳入我们的剂量年定义中,使得氯丙嗪等效物 100mg/天或氟哌啶醇等效物 2mg/天服用 1 年等于 1 个剂量年。
与氯丙嗪和氟哌啶醇的所有比较均具有高度线性,R2 值大于 0.9。幂变换进一步提高了线性度。
通过推导出将剂量转换为氯丙嗪或氟哌啶醇当量的独特公式,我们可以比较原本不同的药物。可以将这些当量乘以个体服用特定剂量的时间,以剂量年来表示(氯丙嗪当量以 mg 为单位)乘以(以年为单位测量的剂量时间)。在将每个剂量转换为剂量年后,可以对结果进行求和,以提供终生暴露的累积定量度量。