Neuroleptic Malignant Syndrome and Atypical Antipsychotic Drugs

Objective: The incidence of neuroleptic malignant syndrome (NMS) is not known, but the frequency of its occurrence with conventional antipsychotic agents has been reported to vary from 0.02% to 2.44%.

Data Sources: MEDLINE search conducted in January 2003 and review of references within the retrieved articles.

Data Synthesis: Our MEDLINE research yielded 68 cases (21 females and 47 males) of NMS associated with atypical antipsychotic drugs (clozapine, N = 21; risperidone, N = 23; olanzapine, N = 19; and quetiapine, N = 5). The fact that 21 cases of NMS with clozapine were found indicates that low occurrence of extrapyramidal symptoms (EPS) and low EPS-inducing potential do not prevent the occurrence of NMS and D₂ dopamine receptor blocking potential does not have direct correlation with the occurrence of NMS. One of the cardinal features of NMS is an increasing manifestation of EPS, and the conventional antipsychotic drugs are known to produce EPS in 95% or more of NMS cases. With atypical antipsychotic drugs, the incidence of EPS during NMS is of a similar magnitude.

Conclusions: For NMS associated with atypical antipsychotic drugs, the mortality rate was lower than that with conventional antipsychotic drugs. However, the mortality rate may simply be a reflection of physicians’ awareness and ensuing early treatment.