How CATIE brought us back to Kansas: a critical re-evaluation of the concept of atypical antipsychotics and their place in the treatment of schizophrenia

Abstract

The subdivision of the class of antipsychotic drugs into two discrete groups – ‘conventional’ (or first generation) and ‘atypical’ (or second generation) – has been adopted as standard, with the latter generally accepted as ‘better’ and widely recommended as automatic first-line choices. However, this perception has been thrown into confusion with the results of large pragmatic trials that failed to identify advantages with the new, more expensive drugs, while identifying worrying tolerability issues. This article explores the origins of ‘atypicality’, its construction on the back of a confusing and weak clinical validator (diminished liability to promote parkinsonism) and how even in relation to the archetypical atypical, clozapine, the uncertain boundaries of drug-induced extrapyramidal dysfunction may be contributing to confusion about ‘efficacy’ and ‘tolerability’. It argues that abandoning atypicality would open up clinical practice to all drugs of a single class of ‘antipsychotics’ and allow for individualised risk/benefit appraisal as a basis for truly tailored treatment recommendations.