Neuroleptic Malignant Syndrome – The Fundamentals

Serotonin syndrome, CNS infections, sepsis, drug-induced hyperthermic syndromes, anticholinergic poisoning, sympathomimetic toxicity, malignant hyperthermia, neuroleptic malignant syndrome

• • NMS is a  complication of antipsychotic drug therapy that usually occurs within the first two weeks of starting the medication, but  can occur at any time, including after dose adjustments
  • It can occur with all the typical antipsychotics like haloperidol or chlorpromazine, and most of the atypical antipsychotics, including aripiprazole, olanzapine, and risperidone

False. It is usually within the therapeutic range

1 to 2 cases per 10,000 patients who are treated with antipsychotics

The presentation involves a tetrad of fever, muscular rigidity (“lead-pipe” and “cogwheel rigidity”), autonomic dysfunction, and altered mental status (including lethargy, agitation, mutism, or coma) that develop over a period of 1 to 3 days

Elevated CK, leukocytosis, transaminitis, hypernatremia or hyponatremia, metabolic acidosis, myoglobinuria, elevated BUN and Cr, and low iron level

• Serotonin Syndrome and NMS commonly present similarly, and in setting of polypharmacy, differentiating them can be very difficult. Both can present with elevated CK and increased tone. It is best to avoid ALL neuroleptics, including haloperidol for agitated patients if there is ANY doubt regarding your diagnosis
  • Serotonin Syndrome usually presents within 24 hours of starting the serotonergic medication; NMS has a variable timeline of presentation
  • Serotonin syndrome may involve myoclonus, hyperreflexia, mydriasis, hyperactive bowel sounds; whereas in NMS, there may be hyporeflexia, normal pupils, normal/decreased bowel sounds

• ABCs first!
  • Some patients may need intubation for airway protection. Also consider paralysis and intubation for hyperthermia and rigidity, as paralysis reduces muscle contraction and lowers temperature.
• Supportive treatment primarily
  • Discontinue all antipsychotics immediately and drugs that can make NMS worse including anticholinergics, antihistamines, or lithium.
  • Reduce the patient’s temperature with external cooling measures.
  • Consider using a benzodiazepine like lorazepam to reduce agitation and sympathetic activity.
• Reduce muscle rigidity with dantrolene 1-2.5 mg/kg IV loading dose then 1 mg/kg IV q6h or bromocriptine 2.5-5 mg PO BID or TID

Rhabdomyolysis, renal failure, respiratory failure, DIC, cardiovascular collapse, and death