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The phenothiazines have exhibited a history of problems associated with the bioequivalence of solid oral dosage forms. The more recent availability of chemically equivalent forms of thioridazine has raised new and interesting questions about the appropriateness of generic product interchange, even among brands that have been designated "therapeutically equivalent" by the Food and Drug Administration. The scrutiny that has accompanied the consideration of thioridazine products for inclusion into various state generic substitution formularies has offered an opportunity to examine issues involving bioequivalency in considerable detail. Specific bioequivalency concerns relate to: correct analysis of drug in biological fluids; the importance of evaluating active metabolites: single-dose vs. multiple-dose crossover studies; appropriate statistical power analysis; the "70/70" rule, and comparison of product variabilities. Examples of problems are cited to illustrate that significant questions still remain about the appropriate factors that should be used to establish bioequivalency.

The phenothiazines are among the most widely used drugs to treat symptoms commonly associated with acute and chronic psychoses. One of the commonly prescribed compounds within this class of drugs is thioridazine, available both as a generic product as well as the innovator product, Mellaril. Each of these products is coded as bioequivalent and consequently therapeutically equivalent by the Food and Drug Administration (FDA). A recent issue of this journal contained an article that raised a number of questions concerning the bioequivalence of the generic versions of thioridazine that have been approved by the FDA. Their article was based in part on information obtained from the FDA as well as information supplied to the authors by Sandoz, Inc., the manufacturer of the original thioridazine drug product Mellaril. The FDA has reviewed its original decision of bioequivalence. Based on this reassessment, the FDA strongly rejects the assertion by the authors that several of the approved generic thioridazine products are not bioequivalent. The rationale behind the FDA decisions and the FDA's viewpoint on the bioequivalence of generic thioridazine drug products is discussed in detail.

Polypharmacy with psychoactive drugs was surveyed in 1276 elderly psychiatric patients from 12 Veterans Administration hospitals. One out of every six patients received two or more psychoactive agents. No specific combination of drugs was overly popular. The most frequently administered combinations, thioridazine plus phenobarbital and chlorpromazine plus phenobarbital, were administered to only 13 patients each (1% of the sample). The large majority of the combinations involved antipsychotic agents. One antipsychotic drug, thioridazine, was a component of nearly one-third of the combinations. The most frequent pairings were an antipsychotic drug plus and antidepressant, two antipsychotic drugs, and an antipsychotic drug plus an antianxiety agent or sedative-hypnotic. The use of polypharmacy was significantly related to patient age. One out of every four patients 60 to 65 years of age received two or more psychoactive drugs compared to only one out of eight over 75 years of age. The implications of these findings for treatment and research are discussed.