Crítica del concepto de antipsicótico atípicouna propuesta de clasificación clínica de los antipsicóticos

Abstract

Introduction. Currently we do not have objective tools to choose antipsychotic drugs. Consequently, their classification and important decisión making about their use is still based on clinical and empirical criteria, and the concepts that define them (therapeutic and secondary effects). With the appearance of chlorpromazine in the 1950s, came the notion of a neuroleptic drug, with which a close relation was observed between the antipsychotic activity and extrapyramidal movements. After the resurgence of clozapine in the nineties, and other antipsychotics that have appeared since, the idea of an atypical antipsychotic (as a modern drug) has prevailed over that of a neuroleptic (classical and obsolete drug). This dichotomous classifaction scheme is debatable, and does not seem to adapt to the level of diversity between antipsychotic drugs. Objectives. Describe and research the emergence, definition and use of the terms “neuroleptic” and “atypical” antipsychotic, and the clinical and pharmacological aspects relevant to them. Analyze data from clinical trials and establish new indexes that better classify antipsychotic drugs regarding the differences between neuroleptic and atypical antipsychotics. The aim is to elucidate if there is a categorical classification model that fits this debate. Material and methods. A historical essay is written that describes and analyzes the evolution of antipsychotic drugs, the clinical concepts that have been used to define them (neuroleptic and atypical antipsychotic) and the new classification that have been proposed in this regard. Efficacy data and data on extrapyramidal symptoms and prolactin levels was obtained from metanalysis of clinical trials on antipsychotics used in schizophrenia. Indexes were established correlating drug effectiveness with observed side effects. Their distribution was analyzed using hierarchical cluster analysis following Ward´s mínimum distance and minimum variance methods with the euclidean distance. Results. The history of antipsychotic treatments is described regarding its most relevant milestones. The use of chlorpromazine in anaesthesia (Laborit, 1951) and the rediscovery of reserpine in Indian medicine, the use of chlorpromazine by Delay and Deniker (1952) and their definition of a neuroleptic antipsychotic drug (1955, 1957) being an drug with extrapiramidal symptoms. The synthesis of haloperidol by Janssen (1959) and its reinforcement of the neuroleptic model. From the 1960s onwards, new drugs emerged that raised doubts about the neuroleptic paradigm, with other antipsychotic drugs such as clozapine (1971) having an atypical effect by not causing extrapyramidal symptoms. Clozapine use was withdrawn due to agranulocytosis, but was then reintroduced in 1989 when superior efficacy was demonstrated in resistant schizophrenia, consolidating the idea of an atypical antipsychotic. The antipsychotics that followed clozapine have been intended to adhere to this scheme, showing advantages, but not a total equivalence with the profile of clozapine. Various classification procedures for antipsychotics are presented. Correlation and cluster analysis of indexes show that antipsychotic drugs are not distributed into two separate homogeneous groups (neuroleptic and atypical antipsychotics). Instead, correlation and cluster analysis of indexes that relate extrapyramidal symptoms with efficacy against positive and negative psychotic symptoms, reveal a linear relationship that allows for the distribution of the drugs in a continuum. Conclusions. The separation of antipsychotic drugs into two groups (neuroleptics vs. atypical antipsychotics), does not reflect their clinical reality. A clinical classification of drugs based on indexes that relate side effects to effectiveness can be useful in clinical practice. The classification proposed in this study is called the extrapyramidal index.