Lessons from the history of antipsychotic discovery: part 2 - dopaminergic diversification

This article examines the development of antipsychotic medications in the period following the discovery of chlorpromazine in the mid-1950s up to the early 21st century. This era is defined by the identification of dopamine modulation as the central mechanism for treating psychosis, and by the development of a diversity of treatments around this mechanism. This strategy yielded a broad range of effective treatments and transformed clinical care; however, with the notable exception of clozapine, it failed to produce substantial gains in overall efficacy. Newer agents primarily differed in tolerability rather than therapeutic impact. Partial dopamine agonists refined, rather than replaced, this approach. As a result, the dopaminergic era offers a cautionary lesson for psychiatric drug development and underscores the need to move beyond dopamine-based models per se.