Neuroleptic Malignant Syndrome: No Longer Exclusively a “Neuroleptic” Phenomenon

Abstract

Objective: To review the literature concerning the incidence of neuroleptic malignant syndrome (NMS) associated with the use of atypical antipsychotics. Data Sources: Cases were identified through a search of MEDLINE (1986–March 2004) using the terms neuroleptic malignant syndrome, antipsychotic, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Study Selection and Data Extraction: Case reports of possible NMS secondary to second-generation antipsychotics were selected for review. Reports meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for NMS were considered. Case reports in which 1 of the 2 major diagnostic criteria was met were also included in the analysis. Furthermore, at least one minor criterion was met. Case reports in which patients received traditional antipsychotics were excluded. Data Synthesis: NMS is a rare and sometimes fatal disease. Several theories exist as to how NMS develops, and an equally large amount of diagnostic criteria are available. However, the majority of available data are based on the first-generation neuroleptics and very few exist with regard to the second-generation antipsychotics. Conclusions: Although there are numerous case reports of NMS occurring secondary to the use of second-generation antipsychotics, the incidence has never been fully elucidated. While the reasons for this remain uncertain, not all cases of second-generation–induced NMS fulfill the diagnostic criteria established for traditional neuroleptics and therefore may not be reported as such.