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Therapeutic Dose Equivalency Calculation Method Proposed for Atypical Antipsychotic Medications

Researchers from Yale University School of Medicine have calculated evidence-based dose equivalence estimates for antipsychotic agents which are consistent across medications and may be useful for clinical and research purposes.

These reported minimum effective doses can be effectively used to calculate dose equivalencies for newer atypical antipsychotics, according to Scott W. Woods, MD.

An estimation of therapeutic dose equivalence across antipsychotic medications is required for several clinical and research applications, however, dose equivalence estimations for newer antipsychotics are not currently well established.

Dr. Woods developed a proxy method in which fixed-dose data drawn from separate drug development programs was used to calculate equivalence ratios.

He collected study data using MEDLINE, the bibliographies of identified reports, published meta-analyses and reviews, Cochrane reviews, Freedom of Information Act material available from the Food and Drug Administration, and abstracts from scientific meetings from 1997 to 2002.

The reported minimum effective doses identified were 4 mg/day for risperidone, 10 mg/day for olanzapine, 150 mg/day for quetiapine, 120 mg/day for ziprasidone, 15 mg/day for aripiprazole, and 4 mg/day for haloperidol.

Haloperidol equivalent doses were estimated from minimum effective doses and converted to chlorpromazine equivalents following the "2 mg of haloperidol equals 100 mg of chlorpromazine" convention. Using this method, chlorpromazine dose estimates were calculated at 2 mg/day for risperidone, 5 mg/day for olanzapine, 75 mg/day for quetiapine, 60 mg/day for ziprasidone, and 7.5 mg/day for aripiprazole.

A limitation to the proposed method of dose calculation is that equivalency at one point in the dose range may not directly translate to equivalency at higher doses.

"An equivalency calculation based on dose-response curves using all the data from all doses could be attempted, but this approach would require making an assumption that the order of the dose response relation (e.g., linear, quadratic) be the same across medications," Dr. Woods points out.

He recommends further research to compare dose equivalencies derived from fixed-dose and flexible-dose calculation methodologies.
J Clin Psychiatry 2003 Jun;64:6:663-7. "Chlorpromazine equivalent doses for the newer atypical antipsychotics"

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