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Is amisulpride associated less with neuroleptic malignant syndrome? Review and hypothesis


Atypical antipsychotics have been reported to induce neuroleptic malignant syndrome (NMS). The precise pathophysiologic mechanism is unknown but dopamine blockage is pivotal. The serotoninergic action of atypical antipsychotics may also been implicated because serotonin may inhibit dopamine release and worsen hypodopaminergic states. Amisulpride, which is a selective D2/D3 receptor antagonist and has no affinity for serotonin receptors may be less associated with the development of NMS.

Materials and methods

A Medline search was conducted for articles published till July 2009 relative to the induction of NMS by atypical antipsychotics in non-geriatric patients with schizophrenia or schizoaffective disorder. We used the key-words neuroleptic malignant syndrome and the names of all first-line atypical antipsychotics, with the exception of paliperidone, which has been recently marketed.


The number of the reported cases of atypical antipsychotic-induced NMS in the defined population was 24 for risperidone, 18 for olanzapine, 7 for quetiapine, 9 for aripiprazole, and 5 for ziprasidone. Only two cases of amisulpride-induced NMS were revealed. In one case the patient was vulnerable to the induction of NMS which had been caused by three different atypical antipsychotics.


In the absence of large prospective studies regarding the induction of NMS by atypical antipsychotics, which are difficult to perform due to the rarity of the syndrome, definite conclusions cannot be reached. Amisulpride may be less than the other atypical antipsychotics associated with NMS, and this may be accounted for by its lack of serotoninergic action. Amisulpride may be a useful option for re-started antipsychotic medication in patients recovering from NMS.

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Correspondence to Vaios Peritogiannis.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Peritogiannis, V., Kalampokis, G. & Lixouriotis, C. Is amisulpride associated less with neuroleptic malignant syndrome? Review and hypothesis. Ann Gen Psychiatry 9, S158 (2010).

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  • Dopamine
  • Schizophrenia
  • Serotonin
  • Risperidone
  • Olanzapine