Fall and Rise of Polypharmacy?

Abstract

Early in the 20th century, in an era before the wide availability of effective drugs with established dose ranges and proven outcomes, the use of multiple drug combinations in individual tablets and capsules, described as polypharmacy, was common. Although there may have been a rational selection of agents sometimes, on more occasions a mixture was developed of dubious efficacy and rationale. With the introduction of specific drug entities with established efficacy and dose ranges in the 1950s and 1960s, there was an academic reaction against these combination products. In many cases, multiple drugs were combined without clear evidence that each contributed to the efficacy of the preparation at least in the dose used. There were justifiable fears that multiple drugs would increase the risk of adverse drug reactions, particularly idiosyncratic or allergic ones. This academic reaction in undergraduate medical schools discouraged combination products and encouraged the use of effective doses of drugs with established actions and mechanisms. Generations of medical graduates from the 1960s, 1970s, and 1980s were presented with a view that polypharmacy was dangerous therapeutics and indefensible practice. Most fixed-drug combination tablets were viewed with suspicion. These attitudes were consolidated by the new policies of drug registration and licensing introduced in many countries in the 1960s. Older multiple drug combinations rarely justified the expensive …