Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective

Abstract

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening side-effect that can occur in response to treatment with antipsychotic drugs. Symptoms commonly include hyperpyrexia, muscle rigidity, autonomic dysfunction and altered mental status. In the current review we provide an overview on past and current developments in understanding the causes and treatment of NMS. Studies on the epidemiological incidence of NMS are evaluated, and we provide new data from the Canada Vigilance Adverse Reaction Online database to elaborate on drug-specific and antipsychotic drug polypharmacy instances of NMS reported between 1965 and 2012. Established risk factors are summarized with an emphasis on pharmacological and environmental causes. Leading theories about the etiopathology of NMS are discussed, including the potential contribution of the impact of dopamine receptor blockade and musculoskeletal fiber toxicity. A clinical perspective is provided whereby the clinical presentation and phenomenology of NMS is detailed, while the diagnosis of NMS and its differential is expounded. Current therapeutic strategies are outlined and the role for both pharmacological and non-pharmacological treatment strategies in alleviating the symptoms of NMS are discussed.

Fig. (1)

Number of cases of NMS associated with atypical antipsychotics reported in the Canada Vigilance Adverse Reaction Online Database.

Fig. (2)

Number of cases of NMS associated with typical antipsychotics reported in the Canada Vigilance Adverse Reaction Online Database.

Fig. (3)

Etiopathogenesis of Neuroleptic Malignant Syndrome and its clinical manifestations. Khaki-coloured boxes describe risk factors associated with NMS, green ovals describe etiopathogenic mechanisms that lead to pathophysiological changes in orange polygons that result in clinical symptomatology in red stars. Abbreviations: ANS, autonomic nervous system; BP, blood pressure; Dp, dopamine; HR, heart rate; RR, respiration rate.