The Neuroleptic Malignant Syndrome (NMS) is a syndrome which may occur in patients receiving neuroleptic agents. Its presentation and symptoms may vary, but the classic tetrad is fever, rigidity, altered sensorium and autonomic dysfunction. It can be fatal if unrecognized. Caroff et al specified diagnostic criteria to aid in its recognition.


Diagnostic Criteria for NMS:

(1) treatment with neuroleptic agent prior to onset

(1a) within 7 days for oral agents

(1b) within 2-4 weeks for depot forms

(2) hyperthermia >= 38°C (may be delayed in onset)

(3) muscle rigidity

(4) 5 or more of the following:

(4a) change in mental status

(4b) tachycardia

(4c) hypertension or hypotension

(4d) tachypnea or hypoxia

(4e) diaphoresis (excessive sweating) or sialorrhea (excessive flow of saliva)

(4f) tremor

(4g) incontinence

(4h) creatine phosphokinase (CK) elevation or myoglobinuria

(4i) leukocytosis

(4j) metabolic acidosis

(5) exclusion of other drug-induced, systemic or neuropsychiatric illnesses


Differential diagnosis:

(1) serotonin syndrome – This does not show muscle rigidity.

(2) anticholinergic syndrome



• This definition requires use of a neuroleptic agent. Other authors include non-neuroleptic agents, but this introduces the problems of differentiation from the other conditions with overlapping symptomatology.


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