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Letter to the Editor

Comments on a Consensus Regarding Diagnostic Criteria for Neuroleptic Malignant Syndrome

Branimir Margetić, MD, and Branka Aukst-Margetić, MD, PhD

Published: February 15, 2012

See related article by Gurrera, et al.

Comments on a Consensus Regarding Diagnostic Criteria for Neuroleptic Malignant Syndrome

To the Editor: A group of distinguished experts on neuroleptic malignant syndrome (NMS) has reached a consensus regarding diagnostic criteria for NMS using the Delphi technique under the coordination of Dr Ronald J. Gurrera.1 It is logical to assume that the use of the Delphi technique would result in a more acceptable set of criteria and probably lead to advantages for future research on NMS.

However, the implementation of this consensus may lead to some important changes and presumed advantages in the understanding of the condition that were not mentioned by the authors. For example, according to DSM-IV-TR, NMS is associated with the use of neuroleptic medication. However, according to this consensus, NMS may be associated with the use of a dopamine antagonist or with dopamine agonist withdrawal. Indirectly, this indicates a consensus that the term neuroleptic malignant syndrome is a misnomer. Therefore, it seems that a different designation for the syndrome would be appropriate, and it would be interesting to see whether a consensus on that issue would be possible.

Furthermore, although the consensus by this group is not related to the nature of the condition, it is worth noting that in dozens of publications NMS is described as an idiosyncratic reaction. However, idiosyncratic reactions are most likely caused by reactive metabolites of some drugs,2 not by drug withdrawals. Accordingly, the group’s inclusion of dopamine agonist withdrawal as a cause of NMS indicates a consensus that NMS is not an idiosyncratic reaction, at least in some cases. However, many aspects of NMS remain controversial.3

The question of fundamental clinical interest is when to start treatment of the condition. Clinicians must not be conservative, but should they treat the condition when no criteria are fulfilled, or even when the development of NMS is only under consideration? Aside from the question of which criteria to use, there is a gap between a need for criteria, which are necessary for improvement of research, and a need for a prompt clinical reaction. Ideally, the treatment of the condition when no criteria are fulfilled should prevent the development of the full-blown picture of NMS. Thus, it is unclear whether the criteria for diagnosis and the criteria for treatment should be the same.


1. Gurrera RJ, Caroff SN, Cohen A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry. 2011;72(9):1222-1228. PubMed doi:10.4088/JCP.10m06438

2. Knowles SR, Uetrecht J, Shear NH. Idiosyncratic drug reactions: the reactive metabolite syndromes. Lancet. 2000;356(9241):1587-1591. doi:10.1016/S0140-6736(00)03137-8 PubMed

3. Margetić B, Aukst-Margetić B. Neuroleptic malignant syndrome and its controversies. Pharmacoepidemiol Drug Saf. 2010;19(5):429-435. PubMed

Branimir Margetić, MD

Branka Aukst-Margetić, MD, PhD

Editor’s note: Dr Gurrera was shown this letter and declined to reply.


Author affiliations: Neuropsychiatric Hospital "Dr Ivan Barbot," Popovača (Dr Margetić); and Department of Psychiatry, University Hospital Zagreb, Zagreb (Dr Aukst-Margetić), Croatia.

Potential conflicts of interest: None reported.

Funding/support: None reported.

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