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Biomed Res Int. 2014;2014:656370. doi: 10.1155/2014/656370. Epub 2014 Jun 3.

Second-generation antipsychotics and extrapyramidal adverse effects.

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Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia.
University Medical Center Hamburg-Eppendorf, Center for Molecular Neurobiology, Falkenried 94, 20251 Hamburg, Germany.
Clinic for Neurology and Psychiatry for Children and Youth, Faculty of Medicine, University of Belgrade, Dr. Subotica 6a, 11000 Belgrade, Serbia.


Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.

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