Excerpt from Neuroleptic Malignant Syndrome

Synonyms, Key Words, and Related Terms: neuroleptic malignant syndrome, neuroleptic medication, NMS, idiosyncratic reaction, muscular rigidity, autonomic dysfunction, haloperidol, fluphenazine, antipsychotic agents, prochlorperazine, promethazine, clozapine, risperidone, metoclopramide, amoxapine, lithium, dopamine D2-receptor antagonist, withdrawal of anti-Parkinson medication, respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, diffuse intravascular coagulation, DIC, rhabdomyolysis, pneumonia, renal failure, seizures, hyperthermia, profuse diaphoresis, sialorrhea, metabolic acidosis, dopamine receptor blockade, impaired temperature regulation

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Background

The neuroleptic malignant syndrome (NMS) is a rare, but life-threatening, idiosyncratic reaction to a neuroleptic medication. The syndrome is characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction.

Although potent neuroleptics (eg, haloperidol, fluphenazine) are more frequently associated with NMS, all antipsychotic agents, typical or atypical, may precipitate the syndrome. For example, these agents have been associated with NMS: prochlorperazine (Compazine), promethazine (Phenergan), clozapine (Clozaril), and risperidone (Risperdal). NMS has also been associated with non-neuroleptic agents that block central dopamine pathways such as metoclopramide (Reglan), amoxapine (Ascendin), and lithium.

Pathophysiology

All medications implicated in NMS have dopamine D2-receptor antagonist properties. NMS has been noted following withdrawal of anti-Parkinson medication. The clinical syndrome is thought to be secondary to decreased dopamine activity in the central nervous system (CNS) either from blockade of dopamine D2-receptors or from decreased availability of dopamine itself, and NMS shares similarities with malignant hyperthermia and the serotonin syndrome. Blockade of dopamine neurotransmission in the nigrostriatum and hypothalamus results in muscular rigidity and altered thermoregulation, respectively. Sympathetic nervous system activation or dysfunction may play a significant role in the pathogenesis of NMS.

Frequency

United States

Incidence is uncommon, with rates ranging from 0.02-12.2% of patients treated with a neuroleptic medication. Prospective studies and pooled data from the literature report an incidence of 0.07-0.2%. Because of increased awareness of this syndrome and efforts at prevention, the incidence is probably less now than in the past.

Mortality/Morbidity

The incidence of mortality, once reported at 20-30% is now estimated at 5-11.6%. Death usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, or diffuse intravascular coagulation (DIC).
Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmias, DIC, and respiratory failure.

Sex

NMS has been reported to be more common in males, most likely because of increased use of neuroleptics in males. The male-to-female ratio is 2:1.

Age

No age predilection for NMS exists. NMS may occur in patients of any age who are receiving neuroleptics or other precipitating medications.

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