Malignant Syndrome

Neuroleptic malignant syndrome (NMS) related to an-tipsychotic use has been documented for decades.1,2 The syndrome, characterized by autonomic dysfunction, muscle rigidity or extrapyramidal symptoms (EPS), hyper-thermia, and mental status changes, is a rare but potentially lethal complication of antipsychotic therapy. The incidence of NMS has been reported to be 0.02–2.44%,3 with the majority of cases occurring in individuals between the ages of 18 and 59 years. There appears to be a slight predomi-nance of the syndrome in males. The underlying mecha-nism for the development of NMS has not been fully eluci-dated; however, it is believed to be related to rapid dopa-mine (D2) blockade from antipsychotics. While the overwhelming majority of reported cases of NMS are due to traditional antipsychotics, there have been a few due to novel antipsychotics, non-antipsychotic dopa-minergic agents such as metoclopramide, and antiemetics such as prochlorperazine.1,2 NMS has also been reported in patients with Parkinson’s disease in whom dopamine ago-nists were rapidly withdrawn.4 Concomitant lithium thera-py has also been implicated in 7–58 % of NMS cases.2 Upon initiating the offending agent or increasing the dose, 66 % of patients reported the onset of NMS symptoms within 2 weeks.2 Ninety-six percent of cases develop with-in 30 days; a few cases can occur after 30 days. Prodromal symptoms may become apparent within hours of begin-ning therapy for some, but the full syndrome develops in approximately 3–5 days.5 Recently, 68 cases of NMS in patients receiving novel antipsychotic agents were reported (clozapine = 21, risperi-done = 23, olanzapine = 19, quetiapine = 5).3 At the time of that report, there were no cases of ziprasidone-induced NMS. Subsequently, there have been 4 published report