Neuroleptic Malignant Syndrome [NMS] and Serotonin Syndrome

These conditions are really rare. I just saw one case of NMS so far. Being able to differentiate between the two conditions is very important.


Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency associated with the use of antipsychotic agents and characterized by a distinctive clinical syndrome.

The diagnosis should be suspected when any two of the four cardinal clinical features (mental status change, rigidity, fever, or dysautonomia) appear in the setting of antipsychotic use or dopamine withdrawal. 


Serotonin syndrome is diagnosed on the basis of clinical findings. UpToDate suggests diagnosing serotonin syndrome using the Hunter Toxicity Criteria Decision Rules. To fulfill the Hunter Criteria, a patient must have taken a serotonergic agent and meet ONE of the following conditions:

●Spontaneous clonuss

●Inducible clonus PLUS agitation or diaphoresis

●Ocular clonus PLUS agitation or diaphoresis

●Tremor PLUS hyperreflexia

●Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or inducible clonus


Hyperthermia, altered mental status, muscle rigidity, leukocytosis, elevated creatine phosphokinase, elevated hepatic transaminases, and metabolic acidosis are seen in severe cases of both conditions.

Altered mental status Altered mental status-agitation, confusion
Autonomic dysfunction Autonomic dysfunction
Tachycardia, tachypnea Tachycardia, tachypnea
less commonly seenShivering
less commonly seen intermittent diffuse involuntary muscle spasms
hyperactive bowel sounds
less commonly seen Neuromuscular excitation-hyperreflexia with 3+ reflexes at the ankles bilaterally and inducible clonus, increased muscle tone
Diaphoresis Diaphoresis
Differentiating FeaturesRigidity of neuroleptic malignant syndrome tends to be characterized by Slow-onset lead pipe rigidity, along with bradykinesia and elevated creatine kinaseAcute symptom onset (usually within 6 hours of a precipitating event)
Hyperreflexia including clonus, myoclonus, and
Normal creatine kinase levels
Treatment D/C the offending drug
Supportive care
Start with benzodiazepines (lorazepam or diazepam) along with dantrolene in moderate or severe cases, followed by the addition of bromocriptine or amantadine. 
D/C the offending drug
Supportive care
Sedation with BZDs
Serotonin antagonists


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