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The 'atypicality' of antipsychotics: a concept re-examined and re-defined

Abstract

Recent clinical trials have raised questions over the perceived advantages of second-generation 'atypical' antipsychotics over those from the first generation. An atypical antipsychotic in its original sense is one that lacks extrapyramidal side effects. However, the addition of other clinical features to the original concept of atypicality, such as efficacy against negative and cognitive symptoms, seems to have become a feature of searches for novel antipsychotics in the past two decades. Although this approach has led to some therapeutic advances, we propose that it has also hampered antipsychotic drug research and that reframing the concept of atypicality could have a key role in making genuine breakthroughs in schizophrenia therapy.

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Figure 1: Current and proposed classification of compounds for the treatment of schizophrenia.
Figure 2: Dopamine receptor binding profiles of three antipsychotic drugs illustrating putative mechanisms of low propensity for extrapyramidal side effects.

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Acknowledgements

This work was partly supported by the German Research Council (DFG), GR1399/4–1 and 4–2.

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Correspondence to Gerhard Gründer.

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Gründer has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Johnson & Johnson, Otsuka and Pfizer. He has also served on the speakers' bureau of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen Cilag, Otsuka, Pfizer, Servier and Wyeth. He has received grant support from Alkermes, Bristol-Myers Squibb, Johnson & Johnson and Pfizer.

Hippius has served as a consultant for Eli Lilly.

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Gründer, G., Hippius, H. & Carlsson, A. The 'atypicality' of antipsychotics: a concept re-examined and re-defined. Nat Rev Drug Discov 8, 197–202 (2009). https://doi.org/10.1038/nrd2806

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