Neuroleptic malignant syndrome (NMS) is a rare and life threatening condition usually defined as a complication of treatment with antipsychotics characterized by severe rigidity, tremor, fever, altered mental status, autonomic dysfunction, and elevated serum creatine phosphokinase and white blood cell count. The literature on this topic is rather extensive, but many aspects related to the syndrome are thought to be controversial. The aim of this paper, written with the clinician in mind, is to summarize some of the most prominent controversies that may have importance in usual clinical practice.

The literature was searched for reviews, reports on the series of cases, individual case reports of NMS, and other clinically and theoretically important information.

There are controversies associated with virtually all important aspects of NMS. At the moment, it is not clear if this drug reaction is idiosyncratic or not, what diagnostic criteria are the most appropriate for usual clinical practice, and it seems that the estimated incidence is not in accordance with the number of treated patients. There are rather different approaches to the pathophysiological mechanisms, differential diagnosis, and treatment.

Some of the controversies related to NMS have an influence on our understanding of the condition and may have importance in clinical practice. There is a need for further research that should elucidate these controversies. Copyright © 2010 John Wiley & Sons, Ltd.