Clozapine: a neuroleptic at risk of provoking neuroleptic malignant syndrome (NMS) or an alternative neuroleptic with positive NMS case histories?

Clozapine is an atypical neuroleptic drug characterised by a striking lack of extrapyramidal side effects. Although these features would seem to make clozapin an unlikely agent for the induction of neuroleptic malignant syndrome (NMS), several putative clozapin-related cases of NMS have recently been reported. A reevaluation of these articles raised some doubts on the causal relationship between clozapin therapy and NMS in most cases. We report on the clinical history of nine consecutive NMS patients who required reinstitution of neuroleptic therapy and received clozapine in our clinic. We conclude (1) that the alleged NMS induction by clozapine monotherapy needs further substantiation and (2) that clozapine should be considered a drug of choice if a psychotic relapse necessitates neuroleptic treatment for patients with a history of NMS.