Happy birthday neuroleptics! 50 years later: la folie du doute.

Given that we are celebrating the 50th birthday of neuroleptics introduction in psychiatry, the author proposes to take a look at certain results related to therapeutic practice. After a brief chronological literature review of the clinical practices and theoretical models that have controlled drug treatment of schizophrenia, the author presents a critical review of four meta-analyses. Since Delay, Deniker and Harl's initial report, the story of neuroleptics comprises several periods. In 1963, the hyper-dopaminergic theory of psychoses was proposed. Another period began with models mainly based on the serotonin/dopamine relative blockade receptor hypothesis. More recently, a new framework to understand the differential effect of antipsychotics is related to the appropriate modulation (e.g., fast dissociation) of the D2 receptor alone. The concept of atypicality has become a new vista for research and to market new compounds. However, after 50 years of neuroleptic drugs, are we able to answer the following simple questions: Are neuroleptics effective in treating schizophrenia? Is there a difference between atypical and conventional neuroleptics? How do the efficacy and safety of newer antipsychotic drugs compare with those of clozapine? Actually, the answers yielded by these simple questions by meta-analysis should elicit in us a good deal of humility. If we wish to base psychiatry on evidence-based medicine, we run a genuine risk in taking a closer look at what has long been considered fact. Each psychiatrist must continue to be critical, sceptical, optimistic (not overoptimistic) and to learn in order to integrate the positive aspects of our growing knowledge base.