Apparent neuroleptic malignant syndrome with clozapine and lithium

Clozapine is an antipsychotic drug reported to be virtually free of extrapyramidal effects. On the basis of this, we hypothesized that it would be unlikely to cause the neuroleptic malignant syndrome (NMS), a rare but severe reaction observed with other antipsychotic drugs. However, when we administered clozapine (in conjunction with lithium) to a patient with a past history of NMS with fluphenazine, the syndrome reappeared after about 3 weeks of treatment. This represents, to our knowledge, the first report of apparent NMS with clozapine.