Controversies in the Pathogenesis of Neuroleptic Malignant Syndrome

Abstract

The neuroleptic malignant syndrome (NMS) is a relatively rare, but probably underrecognized, potentially fatal complication of the use of neuroleptic drugs. This syndrome was first described in the French medical literature with the introduction of neuroleptics in 1960, where it was referred to as “akinetic hypertonic syndrome.” Over the last decade, almost a 1000 cases of NMS have been reported, but many features of this syndrome remain controversial. Indeed, a grading scale of specific signs and symptoms for the diagnosis of NMS and a spectrum of clinical severity are two issues that await resolution. Many diagnostic criteria have been proposed, but no single set of criteria has been adopted for general use. Hence, different presentations of this disorder could explain some contradictory findings associated with NMS: prospective studies have provided disparate estimates of the frequency of NMS, ranging from 0.07% to 2.20% among patients receiving neuroleptic agents; risk factors for NMS vary in different patient populations; the association between NMS and other potentially fatal syndromes such as malignant hyperthermia is unclear.