Are antipsychotic drug dose equivalents derived using the Defined Daily Doses (DDD) method useful in clinical practice?

The concept of antipsychotic dose equivalents is regarded as important and difficult to define. Previous methods and approaches highlighted the fact that a gold standard equivalency did not exist. Three reasons to pursue the development of a gold standard equivalency is to: 1) inform clinical decision-making when switches between antipsychotic agents is necessary; 2) assist in development of treatment guidelines; and 3) inform more accurate comparisons between antipsychotic medications.

The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure.  Although the DDDs were not developed for dose equivalences, this summary can be a useful resource for pharmacovigilance studies.

The sections below are summarized from referenced article “Dose equivalents for antipsychotic drugs: the DDD method” published in Schizophrenia Bulletin (2016)

Basic premise:

• World Health Organization’s Collaborative Center for Drugs Statistic Methodology calculates Defined Daily Doses (DDDs) for most drugs, including 57 antipsychotic drugs.
• The authors set out to calculate dose equivalents based on the DDDs with dose equivalent calculations to 1 mg olanzapine, 1 mg risperidone, 1 mg haloperidol, and 100 mg chlorpromazine.
• Three other methods, “minimum effective dose method,” the “classical mean dose method,” and an international consensus statement were used as comparison.

Defined Daily Doses (DDDs):

• Intended as a standardized measure of drug consumption rather than a measure of dose equivalence
• Assumed to be average maintenance dose per day when the drug is used for the main adult indication
• The main adult indication for antipsychotic medications is “psychosis.”
• The reference point for DDDs is a 70 kg adult male.

 Limitations of use:

• DDDs not developed for use as dose equivalence.
• DDDs do not reflect therapeutic equivalences of comparable drugs. Accurate reflection of what doses are utilized but does not speak to efficacy or adverse side effects at these doses.

Clinical indications:

• DDDs of depot and LAI antipsychotics represented as: average recommended daily dose divided by dosing interval.
• Useful as a dose equivalence if other scientific approaches are not readily available
• Useful for drug utilization research

Practical tools:

• Table 1: DDDs for 1 mg olanzapine
• Supplement: DDDs for Risperidone, Haloperidol, Chlorpromazine

REFERENCES

Leucht, S., Samara, M., Heres, S., & Davis, J. M. (2016). Dose equivalents for antipsychotic drugs: the DDD method. Schizophrenia bulletin, 42(suppl_1), S90-S94.

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