Novel Antipsychotics and the Neuroleptic Malignant Syndrome: A Review and Critique

OBJECTIVE: The authors' goal was to analyze reported cases of neuroleptic malignant syndrome in patients given clozapine and risperidone. METHOD: They assessed 19 cases of clozapine-induced neuroleptic malignant syndrome and 13 cases of risperidone-induced neuroleptic malignant syndrome against three criteria sets and against extent of exclusionary workup and then designated them as high or low probability of being neuroleptic malignant syndrome. RESULTS: Nine of the 19 cases of clozapine-related neuroleptic malignant syndrome and eight of the 13 cases of risperidone-related neuroleptic malignant syndrome were designated as having high probability of being neuroleptic malignant syndrome. The remainder were designated as having low probability because presentations were not linked to treatment or failed to meet criteria for the syndrome. CONCLUSIONS: Neuroleptic malignant syndrome can occur in patients given atypical antipsychotics and resembles "classical" neuroleptic malignant syndrome. However, side effect profiles overlap considerably with neuroleptic malignant syndrome criteria, and atypical antipsychotics may cause neurotoxicities unrelated to (but misattributed as) neuroleptic malignant syndrome. Insufficient evidence exists for "atypical" neuroleptic malignant syndrome with novel antipsychotics.