Elsevier

Biological Psychiatry

Volume 67, Issue 3, 1 February 2010, Pages 255-262
Biological Psychiatry

Archival Report
Antipsychotic Dose Equivalents and Dose-Years: A Standardized Method for Comparing Exposure to Different Drugs

https://doi.org/10.1016/j.biopsych.2009.08.040Get rights and content

Background

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.

Methods

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.

Results

All comparisons to chlorpromazine and haloperidol were highly linear with R2 values greater than .9. A power transformation further improved linearity.

Conclusions

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) × (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.

Section snippets

Methods and Materials

We used Guidelines 5A and 5B derived from the questionnaire in the Kane et al. survey (6). The authors stated regarding Guideline 5A, “We asked the experts to write-in doses of conventional and atypical antipsychotics that they would consider equivalent to a range of haloperidol doses. We used the mean and standard deviations of their responses to generate real-world doses rounded to currently available pill strengths” (5). The same was done with Guideline 5B for risperidone. The charts from

Results

The results of using linear regression to calculate dose equivalents are shown in Table 2. The formula that solves for the drug indicates the derived regression coefficients for the slope and the intercept. Our first step was to evaluate the linearity of our results by examining R2. The formulas for calculating equivalent doses derived from using regression equations based on the Combined Expert Guidelines, as shown in Table 1, were found to be highly linear. R2 values were close to 1 with

Using Dose Equivalents to Determine Values of Comparator Doses in Clinical Trials

An important benefit of deriving an empiric measure of dose equivalents is the ability to compare doses in clinical trials. For example, selection of appropriate doses was an important issue in the influential Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial (7). The designers chose to use dose ranges recommended by each of the manufacturers, average doses prescribed in the United States at the time, and knowledge of clinical practice patterns; additionally a relatively

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