Determination of bioequivalence of psychotropic drugs and concerns involving product interchange.

There is a growing debate among researchers and practitioners concerning the validity of the Food and Drug Administration (FDA) standards for establishing generic interchange through assignment of "therapeutically equivalent" designations for noninnovator or generic drugs. This debate has particular significance for psychotropic drugs which are used in the management of patients with severely debilitating mental diseases. Thus, the controversy primarily focuses on the appropriateness of using the FDA's therapeutic equivalence designation as a criterion for interchange. This is particularly important in light of the lack of well-defined standards for bioequivalence studies and in view of the effect of mandatory substitution laws and financial incentives that encourage generic dispensing that can lead to frequent and indiscriminate interchange among multiple generic brands. Specific concerns include the validity of assay techniques for drug in biologic fluids, statistical power analysis, the appropriateness of the "70/70 rule," and the relevance of studies carried out in healthy normal volunteers in the determination of bioequivalence.