Neuromalignant Syndrome (NMS) and Serotonin Syndrome (SS)

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Differentiating serotonin syndrome and neuroleptic malignant syndrome

NMS Serotonin Syndrome
within 7 days of neuroleptic/increased dose within 24 hours of starting med
dysphagia/hypersalivation/incontinence agitation/diarrhea
hyperthermia/rigidity/rhabdo/akinesia dilated pupils/myoclonus/hyperreflexia

NMS

  • have on radar if being treated with neuroleptics + change in mental status/EPS symptoms (nonresponsive to meds)/autonomic dysfunction
  • classic – hyperthermia, “lead-pipe” rigidity, delirium/catatonia
  • Labs may show: leukocytosis, elevated CK (>4x upper limit), low serum iron, metabolic acidosis (all nonspecific)
  • Always consider: CNS infection, trauma and status epilepticus (neuroleptics also lower seizure thresholds), subcortical lesions, thyrotoxicosis, tetanus, malignant hyperthermia, and others

Criteria for NMS

MAJOR CRITERIA

  • T> 38C (confirmed)
  • Muscle rigidity
  • CPK elevation (5x normal)

MINOR CRITERIA

  • Altered mental status
  • Tachycardia
  • Labile BPs
  • Diaphoresis
  • Tremor
  • Incontinence
  • Leukocytosis
  • Metabolic acidosis

Treatment:

  • Often self-limited with discontinuation of neuroleptics
    • Consider BZDs
    • Consider dantrolene (1-10mg/kg/day in divided doses)
      • risks: hepatic, respiratory compromise
    • Consider Bromocriptine 2-15mg TID
    • Consider Amantadine 200-400mg/day
  • Consider psychiatry consult, particularly for rechallenge

*Mild – supportive care and BZDs

*Mod (rigidity and temps 38-40) – supportive care, BZDs, then Dopamine agonist

*Severe (above + hyper metabolism, temps >40) – above + dantrolene

SS

  • Have this on your radar if > 1 serotonergic agent – SSRI, TCA, MAOIs, linezolid, tramadol
  • severe cases can progress to DIC, ARDS, renal failure
  • if neuroleptic started at this time as well, consider NM
  • Evaluation
    • cognitive/behavioral changes, autonomic instability, neuromuscular abnormalities
    • Labs (all nonspecific, no utility in serum serotonin level): elevated WBC, transaminases, decreased serum bicarb
  • Always consider: infections, metabolic, endocrine, tox
  • Hunter Serotonin Toxicity Criteria:\In presence of serotonergic agent
    • spontaneous clonus = serotonin toxicity
    • inducible clonus AND agitation/diaphoresis = serotonin toxicity
    • ocular clonus AND agitation/diaphoresis = serotonin toxicity
    • tremor AND hyperreflexia = serotonin toxicity
    • hypertonic AND temp > 38 AND ocular/inducible clonus = serotonin toxicity
  • Tx
    • Early recognition, supportive care
    • discontinue offending agents
    • hydrate and cool
    • consider benzodiazepines, cyproheptadine, propranolol, chlorpromazine
    • Consider Psychiatry consults
    • Unlike NMS, need to rechallenge is usually less urgent and can usually be deferred outpatient provider
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